Association Analysis in Rice: From Application to Utilization

PubMed Central

Zhang, Peng; Zhong, Kaizhen; Shahid, Muhammad Qasim; Tong, Hanhua

2016-01-01

Association analysis based on linkage disequilibrium (LD) is an efficient way to dissect complex traits and to identify gene functions in rice. Although association analysis is an effective way to construct fine maps for quantitative traits, there are a few issues which need to be addressed. In this review, we will first summarize type, structure, and LD level of populations used for association analysis of rice, and then discuss the genotyping methods and statistical approaches used for association analysis in rice. Moreover, we will review current shortcomings and benefits of association analysis as well as specific types of future research to overcome these shortcomings. Furthermore, we will analyze the reasons for the underutilization of the results within association analysis in rice breeding. PMID:27582745

Analysis of metabolic syndrome components in >15 000 african americans identifies pleiotropic variants: results from the population architecture using genomics and epidemiology study.

PubMed

Carty, Cara L; Bhattacharjee, Samsiddhi; Haessler, Jeff; Cheng, Iona; Hindorff, Lucia A; Aroda, Vanita; Carlson, Christopher S; Hsu, Chun-Nan; Wilkens, Lynne; Liu, Simin; Selvin, Elizabeth; Jackson, Rebecca; North, Kari E; Peters, Ulrike; Pankow, James S; Chatterjee, Nilanjan; Kooperberg, Charles

2014-08-01

Metabolic syndrome (MetS) refers to the clustering of cardiometabolic risk factors, including dyslipidemia, central adiposity, hypertension, and hyperglycemia, in individuals. Identification of pleiotropic genetic factors associated with MetS traits may shed light on key pathways or mediators underlying MetS. Using the Metabochip array in 15 148 African Americans from the Population Architecture using Genomics and Epidemiology (PAGE) study, we identify susceptibility loci and investigate pleiotropy among genetic variants using a subset-based meta-analysis method, ASsociation-analysis-based-on-subSETs (ASSET). Unlike conventional models that lack power when associations for MetS components are null or have opposite effects, Association-analysis-based-on-subsets uses 1-sided tests to detect positive and negative associations for components separately and combines tests accounting for correlations among components. With Association-analysis-based-on-subsets, we identify 27 single nucleotide polymorphisms in 1 glucose and 4 lipids loci (TCF7L2, LPL, APOA5, CETP, and APOC1/APOE/TOMM40) significantly associated with MetS components overall, all P<2.5e-7, the Bonferroni adjusted P value. Three loci replicate in a Hispanic population, n=5172. A novel African American-specific variant, rs12721054/APOC1, and rs10096633/LPL are associated with ≥3 MetS components. We find additional evidence of pleiotropy for APOE, TOMM40, TCF7L2, and CETP variants, many with opposing effects (eg, the same rs7901695/TCF7L2 allele is associated with increased odds of high glucose and decreased odds of central adiposity). We highlight a method to increase power in large-scale genomic association analyses and report a novel variant associated with all MetS components in African Americans. We also identify pleiotropic associations that may be clinically useful in patient risk profiling and for informing translational research of potential gene targets and medications. © 2014 American Heart Association, Inc.

Variants for HDL-C, LDL-C, and triglycerides identified from admixture mapping and fine-mapping analysis in African American families.

PubMed

Shetty, Priya B; Tang, Hua; Feng, Tao; Tayo, Bamidele; Morrison, Alanna C; Kardia, Sharon L R; Hanis, Craig L; Arnett, Donna K; Hunt, Steven C; Boerwinkle, Eric; Rao, Dabeeru C; Cooper, Richard S; Risch, Neil; Zhu, Xiaofeng

2015-02-01

Admixture mapping of lipids was followed-up by family-based association analysis to identify variants for cardiovascular disease in African Americans. The present study conducted admixture mapping analysis for total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. The analysis was performed in 1905 unrelated African American subjects from the National Heart, Lung and Blood Institute's Family Blood Pressure Program (FBPP). Regions showing admixture evidence were followed-up with family-based association analysis in 3556 African American subjects from the FBPP. The admixture mapping and family-based association analyses were adjusted for age, age(2), sex, body mass index, and genome-wide mean ancestry to minimize the confounding caused by population stratification. Regions that were suggestive of local ancestry association evidence were found on chromosomes 7 (low-density lipoprotein cholesterol), 8 (high-density lipoprotein cholesterol), 14 (triglycerides), and 19 (total cholesterol and triglycerides). In the fine-mapping analysis, 52 939 single-nucleotide polymorphisms (SNPs) were tested and 11 SNPs (8 independent SNPs) showed nominal significant association with high-density lipoprotein cholesterol (2 SNPs), low-density lipoprotein cholesterol (4 SNPs), and triglycerides (5 SNPs). The family data were used in the fine-mapping to identify SNPs that showed novel associations with lipids and regions, including genes with known associations for cardiovascular disease. This study identified regions on chromosomes 7, 8, 14, and 19 and 11 SNPs from the fine-mapping analysis that were associated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides for further studies of cardiovascular disease in African Americans. © 2014 American Heart Association, Inc.

Gay-Straight Alliances are Associated with Lower Levels of School-Based Victimization of LGBTQ+ Youth: A Systematic Review and Meta-analysis.

PubMed

Marx, Robert A; Kettrey, Heather Hensman

2016-07-01

Gay-straight alliances (GSAs) are school-based organizations for lesbian, gay, bisexual, transgender, and queer (LGBTQ+) youth and their allies that often attempt to improve school climate for sexual and gender minority youth. This meta-analysis evaluates the association between school GSA presence and youth's self-reports of school-based victimization by quantitatively synthesizing 15 primary studies with 62,923 participants. Findings indicate GSA presence is associated with significantly lower levels of youth's self-reports of homophobic victimization, fear for safety, and hearing homophobic remarks, and these results are robust, controlling for a variety of study-level factors. The findings of this meta-analysis provide evidence to support GSAs as a means of protecting LGTBQ+ youth from school-based victimization.

A generalized least-squares framework for rare-variant analysis in family data.

PubMed

Li, Dalin; Rotter, Jerome I; Guo, Xiuqing

2014-01-01

Rare variants may, in part, explain some of the hereditability missing in current genome-wide association studies. Many gene-based rare-variant analysis approaches proposed in recent years are aimed at population-based samples, although analysis strategies for family-based samples are clearly warranted since the family-based design has the potential to enhance our ability to enrich for rare causal variants. We have recently developed the generalized least squares, sequence kernel association test, or GLS-SKAT, approach for the rare-variant analyses in family samples, in which the kinship matrix that was computed from the high dimension genetic data was used to decorrelate the family structure. We then applied the SKAT-O approach for gene-/region-based inference in the decorrelated data. In this study, we applied this GLS-SKAT method to the systolic blood pressure data in the simulated family sample distributed by the Genetic Analysis Workshop 18. We compared the GLS-SKAT approach to the rare-variant analysis approach implemented in family-based association test-v1 and demonstrated that the GLS-SKAT approach provides superior power and good control of type I error rate.

Haplotype-based association analysis of general cognitive ability in Generation Scotland, the English Longitudinal Study of Ageing, and UK Biobank.

PubMed

Howard, David M; Adams, Mark J; Clarke, Toni-Kim; Wigmore, Eleanor M; Zeng, Yanni; Hagenaars, Saskia P; Lyall, Donald M; Thomson, Pippa A; Evans, Kathryn L; Porteous, David J; Nagy, Reka; Hayward, Caroline; Haley, Chris S; Smith, Blair H; Murray, Alison D; Batty, G David; Deary, Ian J; McIntosh, Andrew M

2017-01-01

Cognitive ability is a heritable trait with a polygenic architecture, for which several associated variants have been identified using genotype-based and candidate gene approaches. Haplotype-based analyses are a complementary technique that take phased genotype data into account, and potentially provide greater statistical power to detect lower frequency variants. In the present analysis, three cohort studies (n total = 48,002) were utilised: Generation Scotland: Scottish Family Health Study (GS:SFHS), the English Longitudinal Study of Ageing (ELSA), and the UK Biobank. A genome-wide haplotype-based meta-analysis of cognitive ability was performed, as well as a targeted meta-analysis of several gene coding regions. None of the assessed haplotypes provided evidence of a statistically significant association with cognitive ability in either the individual cohorts or the meta-analysis. Within the meta-analysis, the haplotype with the lowest observed P -value overlapped with the D-amino acid oxidase activator ( DAOA ) gene coding region. This coding region has previously been associated with bipolar disorder, schizophrenia and Alzheimer's disease, which have all been shown to impact upon cognitive ability. Another potentially interesting region highlighted within the current genome-wide association analysis (GS:SFHS: P = 4.09 x 10 -7 ), was the butyrylcholinesterase ( BCHE ) gene coding region. The protein encoded by BCHE has been shown to influence the progression of Alzheimer's disease and its role in cognitive ability merits further investigation. Although no evidence was found for any haplotypes with a statistically significant association with cognitive ability, our results did provide further evidence that the genetic variants contributing to the variance of cognitive ability are likely to be of small effect.

Dose-Dependent Associations between Wine Drinking and Breast Cancer Risk - Meta-Analysis Findings.

PubMed

Chen, Jia-Yan; Zhu, Hong-Cheng; Guo, Qing; Shu, Zheng; Bao, Xu-Hui; Sun, Feng; Qin, Qin; Yang, Xi; Zhang, Chi; Cheng, Hong-Yan; Sun, Xin-Chen

2016-01-01

To investigate any potential association between wine and breast cancer risk. We quantitatively assessed associations by conducting a meta-analysis based on evidence from observational studies. In May 2014, we performed electronic searches in PubMed, EmBase and the Cochrane Library to identify studies examining the effect of wine drinking on breast cancer incidence. The relative risk (RR) or odds ratio (OR) were used to measure any such association. The analysis was further stratified by confounding factors that could influence the results. A total of twenty-six studies (eight case-control and eighteen cohort studies) involving 21,149 cases were included in our meta-analysis. Our study demonstrated that wine drinking was associated with breast cancer risk. A 36% increase in breast cancer risk was observed across overall studies based on the highest versus lowest model, with a combined RR of 1.0059 (95%CI 0.97-1.05) in dose-response analysis. However, 5 g/d ethanol from wine seemed to have protective value from our non-linear model. Our findings indicate that wine drinking is associated with breast cancer risk in a dose-dependent manner. High consumption of wine contributes to breast cancer risk with protection exerted by low doses. Further investigations are needed for clarification.

A Method for Gene-Based Pathway Analysis Using Genomewide Association Study Summary Statistics Reveals Nine New Type 1 Diabetes Associations

PubMed Central

Evangelou, Marina; Smyth, Deborah J; Fortune, Mary D; Burren, Oliver S; Walker, Neil M; Guo, Hui; Onengut-Gumuscu, Suna; Chen, Wei-Min; Concannon, Patrick; Rich, Stephen S; Todd, John A; Wallace, Chris

2014-01-01

Pathway analysis can complement point-wise single nucleotide polymorphism (SNP) analysis in exploring genomewide association study (GWAS) data to identify specific disease-associated genes that can be candidate causal genes. We propose a straightforward methodology that can be used for conducting a gene-based pathway analysis using summary GWAS statistics in combination with widely available reference genotype data. We used this method to perform a gene-based pathway analysis of a type 1 diabetes (T1D) meta-analysis GWAS (of 7,514 cases and 9,045 controls). An important feature of the conducted analysis is the removal of the major histocompatibility complex gene region, the major genetic risk factor for T1D. Thirty-one of the 1,583 (2%) tested pathways were identified to be enriched for association with T1D at a 5% false discovery rate. We analyzed these 31 pathways and their genes to identify SNPs in or near these pathway genes that showed potentially novel association with T1D and attempted to replicate the association of 22 SNPs in additional samples. Replication P-values were skewed () with 12 of the 22 SNPs showing . Support, including replication evidence, was obtained for nine T1D associated variants in genes ITGB7 (rs11170466, ), NRP1 (rs722988, ), BAD (rs694739, ), CTSB (rs1296023, ), FYN (rs11964650, ), UBE2G1 (rs9906760, ), MAP3K14 (rs17759555, ), ITGB1 (rs1557150, ), and IL7R (rs1445898, ). The proposed methodology can be applied to other GWAS datasets for which only summary level data are available. PMID:25371288

Walking training associated with virtual reality-based training increases walking speed of individuals with chronic stroke: systematic review with meta-analysis.

PubMed

Rodrigues-Baroni, Juliana M; Nascimento, Lucas R; Ada, Louise; Teixeira-Salmela, Luci F

2014-01-01

To systematically review the available evidence on the efficacy of walking training associated with virtual reality-based training in patients with stroke. The specific questions were: Is walking training associated with virtual reality-based training effective in increasing walking speed after stroke? Is this type of intervention more effective in increasing walking speed, than non-virtual reality-based walking interventions? A systematic review with meta-analysis of randomized clinical trials was conducted. Participants were adults with chronic stroke and the experimental intervention was walking training associated with virtual reality-based training to increase walking speed. The outcome data regarding walking speed were extracted from the eligible trials and were combined using a meta-analysis approach. Seven trials representing eight comparisons were included in this systematic review. Overall, the virtual reality-based training increased walking speed by 0.17 m/s (IC 95% 0.08 to 0.26), compared with placebo/nothing or non-walking interventions. In addition, the virtual reality-based training increased walking speed by 0.15 m/s (IC 95% 0.05 to 0.24), compared with non-virtual reality walking interventions. This review provided evidence that walking training associated with virtual reality-based training was effective in increasing walking speed after stroke, and resulted in better results than non-virtual reality interventions.

Walking training associated with virtual reality-based training increases walking speed of individuals with chronic stroke: systematic review with meta-analysis

PubMed Central

Rodrigues-Baroni, Juliana M.; Nascimento, Lucas R.; Ada, Louise; Teixeira-Salmela, Luci F.

2014-01-01

OBJECTIVE: To systematically review the available evidence on the efficacy of walking training associated with virtual reality-based training in patients with stroke. The specific questions were: Is walking training associated with virtual reality-based training effective in increasing walking speed after stroke? Is this type of intervention more effective in increasing walking speed, than non-virtual reality-based walking interventions? METHOD: A systematic review with meta-analysis of randomized clinical trials was conducted. Participants were adults with chronic stroke and the experimental intervention was walking training associated with virtual reality-based training to increase walking speed. The outcome data regarding walking speed were extracted from the eligible trials and were combined using a meta-analysis approach. RESULTS: Seven trials representing eight comparisons were included in this systematic review. Overall, the virtual reality-based training increased walking speed by 0.17 m/s (IC 95% 0.08 to 0.26), compared with placebo/nothing or non-walking interventions. In addition, the virtual reality-based training increased walking speed by 0.15 m/s (IC 95% 0.05 to 0.24), compared with non-virtual reality walking interventions. CONCLUSIONS: This review provided evidence that walking training associated with virtual reality-based training was effective in increasing walking speed after stroke, and resulted in better results than non-virtual reality interventions. PMID:25590442

75 FR 8239 - School Food Safety Program Based on Hazard Analysis and Critical Control Point Principles (HACCP...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-24

... 0584-AD65 School Food Safety Program Based on Hazard Analysis and Critical Control Point Principles... Safety Program Based on Hazard Analysis and Critical Control Point Principles (HACCP) was published on... of Management and Budget (OMB) cleared the associated information collection requirements (ICR) on...

Gene-set analysis based on the pharmacological profiles of drugs to identify repurposing opportunities in schizophrenia.

PubMed

de Jong, Simone; Vidler, Lewis R; Mokrab, Younes; Collier, David A; Breen, Gerome

2016-08-01

Genome-wide association studies (GWAS) have identified thousands of novel genetic associations for complex genetic disorders, leading to the identification of potential pharmacological targets for novel drug development. In schizophrenia, 108 conservatively defined loci that meet genome-wide significance have been identified and hundreds of additional sub-threshold associations harbour information on the genetic aetiology of the disorder. In the present study, we used gene-set analysis based on the known binding targets of chemical compounds to identify the 'drug pathways' most strongly associated with schizophrenia-associated genes, with the aim of identifying potential drug repositioning opportunities and clues for novel treatment paradigms, especially in multi-target drug development. We compiled 9389 gene sets (2496 with unique gene content) and interrogated gene-based p-values from the PGC2-SCZ analysis. Although no single drug exceeded experiment wide significance (corrected p<0.05), highly ranked gene-sets reaching suggestive significance including the dopamine receptor antagonists metoclopramide and trifluoperazine and the tyrosine kinase inhibitor neratinib. This is a proof of principle analysis showing the potential utility of GWAS data of schizophrenia for the direct identification of candidate drugs and molecules that show polypharmacy. © The Author(s) 2016.

Analysis of whole exome sequencing with cardiometabolic traits using family-based linkage and association in the IRAS Family Study

PubMed Central

Tabb, Keri L.; Hellwege, Jacklyn N.; Palmer, Nicholette D.; Dimitrov, Latchezar; Sajuthi, Satria; Taylor, Kent D.; NG, Maggie C.Y.; Hawkins, Gregory A.; Chen, Yii-Der Ida; Brown, W. Mark; McWilliams, David; Williams, Adrienne; Lorenzo, Carlos; Norris, Jill M.; Long, Jirong; Rotter, Jerome I.; Curran, Joanne E.; Blangero, John; Wagenknecht, Lynne E.; Langefeld, Carl D.; Bowden, Donald W.

2017-01-01

Summary Family-based methods are a potentially powerful tool to identify trait-defining genetic variants in extended families, particularly when used to complement conventional association analysis. We utilized two-point linkage analysis and single variant association analysis to evaluate whole exome sequencing (WES) data from 1,205 Hispanic Americans (78 families) from the Insulin Resistance Atherosclerosis Family Study. WES identified 211,612 variants above the minor allele frequency threshold of ≥0.005. These variants were tested for linkage and/or association with 50 cardiometabolic traits after quality control checks. Two-point linkage analysis yielded 10,580,600 LOD scores with 1,148 LOD scores ≥3, 183 LOD scores ≥4, and 29 LOD scores ≥5. The maximal novel LOD score was 5.50 for rs2289043:T>C, in UNC5C with subcutaneous adipose tissue volume. Association analysis identified 13 variants attaining genome-wide significance (p<5×10-08), with the strongest association between rs651821:C>T in APOA5, and triglyceride levels (p=3.67×10-10). Overall, there was a 5.2-fold increase in the number of informative variants detected by WES compared to exome chip analysis in this population, nearly 30% of which were novel variants relative to dbSNP build 138. Thus, integration of results from two-point linkage and single-variant association analysis from WES data enabled identification of novel signals potentially contributing to cardiometabolic traits. PMID:28067407

Tissue Non-Specific Genes and Pathways Associated with Diabetes: An Expression Meta-Analysis.

PubMed

Mei, Hao; Li, Lianna; Liu, Shijian; Jiang, Fan; Griswold, Michael; Mosley, Thomas

2017-01-21

We performed expression studies to identify tissue non-specific genes and pathways of diabetes by meta-analysis. We searched curated datasets of the Gene Expression Omnibus (GEO) database and identified 13 and five expression studies of diabetes and insulin responses at various tissues, respectively. We tested differential gene expression by empirical Bayes-based linear method and investigated gene set expression association by knowledge-based enrichment analysis. Meta-analysis by different methods was applied to identify tissue non-specific genes and gene sets. We also proposed pathway mapping analysis to infer functions of the identified gene sets, and correlation and independent analysis to evaluate expression association profile of genes and gene sets between studies and tissues. Our analysis showed that PGRMC1 and HADH genes were significant over diabetes studies, while IRS1 and MPST genes were significant over insulin response studies, and joint analysis showed that HADH and MPST genes were significant over all combined data sets. The pathway analysis identified six significant gene sets over all studies. The KEGG pathway mapping indicated that the significant gene sets are related to diabetes pathogenesis. The results also presented that 12.8% and 59.0% pairwise studies had significantly correlated expression association for genes and gene sets, respectively; moreover, 12.8% pairwise studies had independent expression association for genes, but no studies were observed significantly different for expression association of gene sets. Our analysis indicated that there are both tissue specific and non-specific genes and pathways associated with diabetes pathogenesis. Compared to the gene expression, pathway association tends to be tissue non-specific, and a common pathway influencing diabetes development is activated through different genes at different tissues.

Dynamic association rules for gene expression data analysis.

PubMed

Chen, Shu-Chuan; Tsai, Tsung-Hsien; Chung, Cheng-Han; Li, Wen-Hsiung

2015-10-14

The purpose of gene expression analysis is to look for the association between regulation of gene expression levels and phenotypic variations. This association based on gene expression profile has been used to determine whether the induction/repression of genes correspond to phenotypic variations including cell regulations, clinical diagnoses and drug development. Statistical analyses on microarray data have been developed to resolve gene selection issue. However, these methods do not inform us of causality between genes and phenotypes. In this paper, we propose the dynamic association rule algorithm (DAR algorithm) which helps ones to efficiently select a subset of significant genes for subsequent analysis. The DAR algorithm is based on association rules from market basket analysis in marketing. We first propose a statistical way, based on constructing a one-sided confidence interval and hypothesis testing, to determine if an association rule is meaningful. Based on the proposed statistical method, we then developed the DAR algorithm for gene expression data analysis. The method was applied to analyze four microarray datasets and one Next Generation Sequencing (NGS) dataset: the Mice Apo A1 dataset, the whole genome expression dataset of mouse embryonic stem cells, expression profiling of the bone marrow of Leukemia patients, Microarray Quality Control (MAQC) data set and the RNA-seq dataset of a mouse genomic imprinting study. A comparison of the proposed method with the t-test on the expression profiling of the bone marrow of Leukemia patients was conducted. We developed a statistical way, based on the concept of confidence interval, to determine the minimum support and minimum confidence for mining association relationships among items. With the minimum support and minimum confidence, one can find significant rules in one single step. The DAR algorithm was then developed for gene expression data analysis. Four gene expression datasets showed that the proposed DAR algorithm not only was able to identify a set of differentially expressed genes that largely agreed with that of other methods, but also provided an efficient and accurate way to find influential genes of a disease. In the paper, the well-established association rule mining technique from marketing has been successfully modified to determine the minimum support and minimum confidence based on the concept of confidence interval and hypothesis testing. It can be applied to gene expression data to mine significant association rules between gene regulation and phenotype. The proposed DAR algorithm provides an efficient way to find influential genes that underlie the phenotypic variance.

The association between mood state and chronobiological characteristics in bipolar I disorder: a naturalistic, variable cluster analysis-based study.

PubMed

Gonzalez, Robert; Suppes, Trisha; Zeitzer, Jamie; McClung, Colleen; Tamminga, Carol; Tohen, Mauricio; Forero, Angelica; Dwivedi, Alok; Alvarado, Andres

2018-02-19

Multiple types of chronobiological disturbances have been reported in bipolar disorder, including characteristics associated with general activity levels, sleep, and rhythmicity. Previous studies have focused on examining the individual relationships between affective state and chronobiological characteristics. The aim of this study was to conduct a variable cluster analysis in order to ascertain how mood states are associated with chronobiological traits in bipolar I disorder (BDI). We hypothesized that manic symptomatology would be associated with disturbances of rhythm. Variable cluster analysis identified five chronobiological clusters in 105 BDI subjects. Cluster 1, comprising subjective sleep quality was associated with both mania and depression. Cluster 2, which comprised variables describing the degree of rhythmicity, was associated with mania. Significant associations between mood state and cluster analysis-identified chronobiological variables were noted. Disturbances of mood were associated with subjectively assessed sleep disturbances as opposed to objectively determined, actigraphy-based sleep variables. No associations with general activity variables were noted. Relationships between gender and medication classes in use and cluster analysis-identified chronobiological characteristics were noted. Exploratory analyses noted that medication class had a larger impact on these relationships than the number of psychiatric medications in use. In a BDI sample, variable cluster analysis was able to group related chronobiological variables. The results support our primary hypothesis that mood state, particularly mania, is associated with chronobiological disturbances. Further research is required in order to define these relationships and to determine the directionality of the associations between mood state and chronobiological characteristics.

A simulations approach for meta-analysis of genetic association studies based on additive genetic model.

PubMed

John, Majnu; Lencz, Todd; Malhotra, Anil K; Correll, Christoph U; Zhang, Jian-Ping

2018-06-01

Meta-analysis of genetic association studies is being increasingly used to assess phenotypic differences between genotype groups. When the underlying genetic model is assumed to be dominant or recessive, assessing the phenotype differences based on summary statistics, reported for individual studies in a meta-analysis, is a valid strategy. However, when the genetic model is additive, a similar strategy based on summary statistics will lead to biased results. This fact about the additive model is one of the things that we establish in this paper, using simulations. The main goal of this paper is to present an alternate strategy for the additive model based on simulating data for the individual studies. We show that the alternate strategy is far superior to the strategy based on summary statistics.

Involvement of the anterior cingulate cortex in time-based prospective memory task monitoring: An EEG analysis of brain sources using Independent Component and Measure Projection Analysis

PubMed Central

Burgos, Pablo; Kilborn, Kerry; Evans, Jonathan J.

2017-01-01

Objective Time-based prospective memory (PM), remembering to do something at a particular moment in the future, is considered to depend upon self-initiated strategic monitoring, involving a retrieval mode (sustained maintenance of the intention) plus target checking (intermittent time checks). The present experiment was designed to explore what brain regions and brain activity are associated with these components of strategic monitoring in time-based PM tasks. Method 24 participants were asked to reset a clock every four minutes, while performing a foreground ongoing word categorisation task. EEG activity was recorded and data were decomposed into source-resolved activity using Independent Component Analysis. Common brain regions across participants, associated with retrieval mode and target checking, were found using Measure Projection Analysis. Results Participants decreased their performance on the ongoing task when concurrently performed with the time-based PM task, reflecting an active retrieval mode that relied on withdrawal of limited resources from the ongoing task. Brain activity, with its source in or near the anterior cingulate cortex (ACC), showed changes associated with an active retrieval mode including greater negative ERP deflections, decreased theta synchronization, and increased alpha suppression for events locked to the ongoing task while maintaining a time-based intention. Activity in the ACC was also associated with time-checks and found consistently across participants; however, we did not find an association with time perception processing per se. Conclusion The involvement of the ACC in both aspects of time-based PM monitoring may be related to different functions that have been attributed to it: strategic control of attention during the retrieval mode (distributing attentional resources between the ongoing task and the time-based task) and anticipatory/decision making processing associated with clock-checks. PMID:28863146

Test-retest reliability of computer-based video analysis of general movements in healthy term-born infants.

PubMed

Valle, Susanne Collier; Støen, Ragnhild; Sæther, Rannei; Jensenius, Alexander Refsum; Adde, Lars

2015-10-01

A computer-based video analysis has recently been presented for quantitative assessment of general movements (GMs). This method's test-retest reliability, however, has not yet been evaluated. The aim of the current study was to evaluate the test-retest reliability of computer-based video analysis of GMs, and to explore the association between computer-based video analysis and the temporal organization of fidgety movements (FMs). Test-retest reliability study. 75 healthy, term-born infants were recorded twice the same day during the FMs period using a standardized video set-up. The computer-based movement variables "quantity of motion mean" (Qmean), "quantity of motion standard deviation" (QSD) and "centroid of motion standard deviation" (CSD) were analyzed, reflecting the amount of motion and the variability of the spatial center of motion of the infant, respectively. In addition, the association between the variable CSD and the temporal organization of FMs was explored. Intraclass correlation coefficients (ICC 1.1 and ICC 3.1) were calculated to assess test-retest reliability. The ICC values for the variables CSD, Qmean and QSD were 0.80, 0.80 and 0.86 for ICC (1.1), respectively; and 0.80, 0.86 and 0.90 for ICC (3.1), respectively. There were significantly lower CSD values in the recordings with continual FMs compared to the recordings with intermittent FMs (p<0.05). This study showed high test-retest reliability of computer-based video analysis of GMs, and a significant association between our computer-based video analysis and the temporal organization of FMs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

GAC: Gene Associations with Clinical, a web based application.

PubMed

Zhang, Xinyan; Rupji, Manali; Kowalski, Jeanne

2017-01-01

We present GAC, a shiny R based tool for interactive visualization of clinical associations based on high-dimensional data. The tool provides a web-based suite to perform supervised principal component analysis (SuperPC), an approach that uses both high-dimensional data, such as gene expression, combined with clinical data to infer clinical associations. We extended the approach to address binary outcomes, in addition to continuous and time-to-event data in our package, thereby increasing the use and flexibility of SuperPC.  Additionally, the tool provides an interactive visualization for summarizing results based on a forest plot for both binary and time-to-event data.  In summary, the GAC suite of tools provide a one stop shop for conducting statistical analysis to identify and visualize the association between a clinical outcome of interest and high-dimensional data types, such as genomic data. Our GAC package has been implemented in R and is available via http://shinygispa.winship.emory.edu/GAC/. The developmental repository is available at https://github.com/manalirupji/GAC.

Imputation-Based Meta-Analysis of Severe Malaria in Three African Populations

PubMed Central

Band, Gavin; Le, Quang Si; Jostins, Luke; Pirinen, Matti; Kivinen, Katja; Jallow, Muminatou; Sisay-Joof, Fatoumatta; Bojang, Kalifa; Pinder, Margaret; Sirugo, Giorgio; Conway, David J.; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Taylor, Terrie; Ndila, Carolyne; Peshu, Norbert; Marsh, Kevin; Williams, Thomas N.; Alcock, Daniel; Andrews, Robert; Edkins, Sarah; Gray, Emma; Hubbart, Christina; Jeffreys, Anna; Rowlands, Kate; Schuldt, Kathrin; Clark, Taane G.; Small, Kerrin S.; Teo, Yik Ying; Kwiatkowski, Dominic P.; Rockett, Kirk A.; Barrett, Jeffrey C.; Spencer, Chris C. A.

2013-01-01

Combining data from genome-wide association studies (GWAS) conducted at different locations, using genotype imputation and fixed-effects meta-analysis, has been a powerful approach for dissecting complex disease genetics in populations of European ancestry. Here we investigate the feasibility of applying the same approach in Africa, where genetic diversity, both within and between populations, is far more extensive. We analyse genome-wide data from approximately 5,000 individuals with severe malaria and 7,000 population controls from three different locations in Africa. Our results show that the standard approach is well powered to detect known malaria susceptibility loci when sample sizes are large, and that modern methods for association analysis can control the potential confounding effects of population structure. We show that pattern of association around the haemoglobin S allele differs substantially across populations due to differences in haplotype structure. Motivated by these observations we consider new approaches to association analysis that might prove valuable for multicentre GWAS in Africa: we relax the assumptions of SNP–based fixed effect analysis; we apply Bayesian approaches to allow for heterogeneity in the effect of an allele on risk across studies; and we introduce a region-based test to allow for heterogeneity in the location of causal alleles. PMID:23717212

Temporal patterns of variable relationships in person-oriented research: longitudinal models of configural frequency analysis.

PubMed

von Eye, Alexander; Mun, Eun Young; Bogat, G Anne

2008-03-01

This article reviews the premises of configural frequency analysis (CFA), including methods of choosing significance tests and base models, as well as protecting alpha, and discusses why CFA is a useful approach when conducting longitudinal person-oriented research. CFA operates at the manifest variable level. Longitudinal CFA seeks to identify those temporal patterns that stand out as more frequent (CFA types) or less frequent (CFA antitypes) than expected with reference to a base model. A base model that has been used frequently in CFA applications, prediction CFA, and a new base model, auto-association CFA, are discussed for analysis of cross-classifications of longitudinal data. The former base model takes the associations among predictors and among criteria into account. The latter takes the auto-associations among repeatedly observed variables into account. Application examples of each are given using data from a longitudinal study of domestic violence. It is demonstrated that CFA results are not redundant with results from log-linear modeling or multinomial regression and that, of these approaches, CFA shows particular utility when conducting person-oriented research.

Do Concomitant Cranium and Axis Injuries Predict Worse Outcome? A Trauma Database Quantitative Analysis

PubMed Central

Chittiboina, Prashant; Banerjee, Anirban Deep; Nanda, Anil

2011-01-01

We performed a trauma database analysis to identify the effect of concomitant cranial injuries on outcome in patients with fractures of the axis. We identified patients with axis fractures over a 14-year period. A binary outcome measure was used. Univariate and multiple logistic regression analysis were performed. There were 259 cases with axis fractures. Closed head injury was noted in 57% and skull base trauma in 14%. Death occurred in 17 cases (6%). Seventy-two percent had good outcome. Presence of abnormal computed tomography head findings, skull base fractures, and visceral injury was significantly associated with poor outcome. Skull base injury in association with fractures of the axis is a significant independent predictor of worse outcomes, irrespective of the severity of the head injury. We propose that presence of concomitant cranial and upper vertebral injuries require careful evaluation in view of the associated poor prognosis. PMID:22470268

Pathway analyses and understanding disease associations

PubMed Central

Liu, Yu; Chance, Mark R

2013-01-01

High throughput technologies have been applied to investigate the underlying mechanisms of complex diseases, identify disease-associations and help to improve treatment. However it is challenging to derive biological insight from conventional single gene based analysis of “omics” data from high throughput experiments due to sample and patient heterogeneity. To address these challenges, many novel pathway and network based approaches were developed to integrate various “omics” data, such as gene expression, copy number alteration, Genome Wide Association Studies, and interaction data. This review will cover recent methodological developments in pathway analysis for the detection of dysregulated interactions and disease-associated subnetworks, prioritization of candidate disease genes, and disease classifications. For each application, we will also discuss the associated challenges and potential future directions. PMID:24319650

An efficient Bayesian meta-analysis approach for studying cross-phenotype genetic associations

PubMed Central

Majumdar, Arunabha; Haldar, Tanushree; Bhattacharya, Sourabh; Witte, John S.

2018-01-01

Simultaneous analysis of genetic associations with multiple phenotypes may reveal shared genetic susceptibility across traits (pleiotropy). For a locus exhibiting overall pleiotropy, it is important to identify which specific traits underlie this association. We propose a Bayesian meta-analysis approach (termed CPBayes) that uses summary-level data across multiple phenotypes to simultaneously measure the evidence of aggregate-level pleiotropic association and estimate an optimal subset of traits associated with the risk locus. This method uses a unified Bayesian statistical framework based on a spike and slab prior. CPBayes performs a fully Bayesian analysis by employing the Markov Chain Monte Carlo (MCMC) technique Gibbs sampling. It takes into account heterogeneity in the size and direction of the genetic effects across traits. It can be applied to both cohort data and separate studies of multiple traits having overlapping or non-overlapping subjects. Simulations show that CPBayes can produce higher accuracy in the selection of associated traits underlying a pleiotropic signal than the subset-based meta-analysis ASSET. We used CPBayes to undertake a genome-wide pleiotropic association study of 22 traits in the large Kaiser GERA cohort and detected six independent pleiotropic loci associated with at least two phenotypes. This includes a locus at chromosomal region 1q24.2 which exhibits an association simultaneously with the risk of five different diseases: Dermatophytosis, Hemorrhoids, Iron Deficiency, Osteoporosis and Peripheral Vascular Disease. We provide an R-package ‘CPBayes’ implementing the proposed method. PMID:29432419

A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.

PubMed

Nikpay, Majid; Goel, Anuj; Won, Hong-Hee; Hall, Leanne M; Willenborg, Christina; Kanoni, Stavroula; Saleheen, Danish; Kyriakou, Theodosios; Nelson, Christopher P; Hopewell, Jemma C; Webb, Thomas R; Zeng, Lingyao; Dehghan, Abbas; Alver, Maris; Armasu, Sebastian M; Auro, Kirsi; Bjonnes, Andrew; Chasman, Daniel I; Chen, Shufeng; Ford, Ian; Franceschini, Nora; Gieger, Christian; Grace, Christopher; Gustafsson, Stefan; Huang, Jie; Hwang, Shih-Jen; Kim, Yun Kyoung; Kleber, Marcus E; Lau, King Wai; Lu, Xiangfeng; Lu, Yingchang; Lyytikäinen, Leo-Pekka; Mihailov, Evelin; Morrison, Alanna C; Pervjakova, Natalia; Qu, Liming; Rose, Lynda M; Salfati, Elias; Saxena, Richa; Scholz, Markus; Smith, Albert V; Tikkanen, Emmi; Uitterlinden, Andre; Yang, Xueli; Zhang, Weihua; Zhao, Wei; de Andrade, Mariza; de Vries, Paul S; van Zuydam, Natalie R; Anand, Sonia S; Bertram, Lars; Beutner, Frank; Dedoussis, George; Frossard, Philippe; Gauguier, Dominique; Goodall, Alison H; Gottesman, Omri; Haber, Marc; Han, Bok-Ghee; Huang, Jianfeng; Jalilzadeh, Shapour; Kessler, Thorsten; König, Inke R; Lannfelt, Lars; Lieb, Wolfgang; Lind, Lars; Lindgren, Cecilia M; Lokki, Marja-Liisa; Magnusson, Patrik K; Mallick, Nadeem H; Mehra, Narinder; Meitinger, Thomas; Memon, Fazal-Ur-Rehman; Morris, Andrew P; Nieminen, Markku S; Pedersen, Nancy L; Peters, Annette; Rallidis, Loukianos S; Rasheed, Asif; Samuel, Maria; Shah, Svati H; Sinisalo, Juha; Stirrups, Kathleen E; Trompet, Stella; Wang, Laiyuan; Zaman, Khan S; Ardissino, Diego; Boerwinkle, Eric; Borecki, Ingrid B; Bottinger, Erwin P; Buring, Julie E; Chambers, John C; Collins, Rory; Cupples, L Adrienne; Danesh, John; Demuth, Ilja; Elosua, Roberto; Epstein, Stephen E; Esko, Tõnu; Feitosa, Mary F; Franco, Oscar H; Franzosi, Maria Grazia; Granger, Christopher B; Gu, Dongfeng; Gudnason, Vilmundur; Hall, Alistair S; Hamsten, Anders; Harris, Tamara B; Hazen, Stanley L; Hengstenberg, Christian; Hofman, Albert; Ingelsson, Erik; Iribarren, Carlos; Jukema, J Wouter; Karhunen, Pekka J; Kim, Bong-Jo; Kooner, Jaspal S; Kullo, Iftikhar J; Lehtimäki, Terho; Loos, Ruth J F; Melander, Olle; Metspalu, Andres; März, Winfried; Palmer, Colin N; Perola, Markus; Quertermous, Thomas; Rader, Daniel J; Ridker, Paul M; Ripatti, Samuli; Roberts, Robert; Salomaa, Veikko; Sanghera, Dharambir K; Schwartz, Stephen M; Seedorf, Udo; Stewart, Alexandre F; Stott, David J; Thiery, Joachim; Zalloua, Pierre A; O'Donnell, Christopher J; Reilly, Muredach P; Assimes, Themistocles L; Thompson, John R; Erdmann, Jeanette; Clarke, Robert; Watkins, Hugh; Kathiresan, Sekar; McPherson, Ruth; Deloukas, Panos; Schunkert, Heribert; Samani, Nilesh J; Farrall, Martin

2015-10-01

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.

A novel method to identify pathways associated with renal cell carcinoma based on a gene co-expression network

PubMed Central

RUAN, XIYUN; LI, HONGYUN; LIU, BO; CHEN, JIE; ZHANG, SHIBAO; SUN, ZEQIANG; LIU, SHUANGQING; SUN, FAHAI; LIU, QINGYONG

2015-01-01

The aim of the present study was to develop a novel method for identifying pathways associated with renal cell carcinoma (RCC) based on a gene co-expression network. A framework was established where a co-expression network was derived from the database as well as various co-expression approaches. First, the backbone of the network based on differentially expressed (DE) genes between RCC patients and normal controls was constructed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The differentially co-expressed links were detected by Pearson’s correlation, the empirical Bayesian (EB) approach and Weighted Gene Co-expression Network Analysis (WGCNA). The co-expressed gene pairs were merged by a rank-based algorithm. We obtained 842; 371; 2,883 and 1,595 co-expressed gene pairs from the co-expression networks of the STRING database, Pearson’s correlation EB method and WGCNA, respectively. Two hundred and eighty-one differentially co-expressed (DC) gene pairs were obtained from the merged network using this novel method. Pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and the network enrichment analysis (NEA) method were performed to verify feasibility of the merged method. Results of the KEGG and NEA pathway analyses showed that the network was associated with RCC. The suggested method was computationally efficient to identify pathways associated with RCC and has been identified as a useful complement to traditional co-expression analysis. PMID:26058425

Use of Language Sample Analysis by School-Based SLPs: Results of a Nationwide Survey

ERIC Educational Resources Information Center

Pavelko, Stacey L.; Owens, Robert E., Jr.; Ireland, Marie; Hahs-Vaughn, Debbie L.

2016-01-01

Purpose: This article examines use of language sample analysis (LSA) by school-based speech-language pathologists (SLPs), including characteristics of language samples, methods of transcription and analysis, barriers to LSA use, and factors affecting LSA use, such as American Speech-Language-Hearing Association certification, number of years'…

Analysis of Rare, Exonic Variation amongst Subjects with Autism Spectrum Disorders and Population Controls

PubMed Central

Liu, Li; Sabo, Aniko; Neale, Benjamin M.; Nagaswamy, Uma; Stevens, Christine; Lim, Elaine; Bodea, Corneliu A.; Muzny, Donna; Reid, Jeffrey G.; Banks, Eric; Coon, Hillary; DePristo, Mark; Dinh, Huyen; Fennel, Tim; Flannick, Jason; Gabriel, Stacey; Garimella, Kiran; Gross, Shannon; Hawes, Alicia; Lewis, Lora; Makarov, Vladimir; Maguire, Jared; Newsham, Irene; Poplin, Ryan; Ripke, Stephan; Shakir, Khalid; Samocha, Kaitlin E.; Wu, Yuanqing; Boerwinkle, Eric; Buxbaum, Joseph D.; Cook, Edwin H.; Devlin, Bernie; Schellenberg, Gerard D.; Sutcliffe, James S.; Daly, Mark J.; Gibbs, Richard A.; Roeder, Kathryn

2013-01-01

We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis) or should data be combined and then analyzed (mega-analysis)? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD. PMID:23593035

A Path Analysis of Latino Parental, Teenager and Cultural Variables in Teenagers' Sexual Attitudes, Norms, Self-Efficacy, and Sexual Intentions.

PubMed

Gaioso, Vanessa Pirani; Villarruel, Antonia Maria; Wilson, Lynda Anne; Azuero, Andres; Childs, Gwendolyn Denice; Davies, Susan Lane

2015-01-01

to test a theoretical model based on the Parent-Based Expansion of the Theory of Planned Behavior examining relation between selected parental, teenager and cultural variables and Latino teenagers' intentions to engage in sexual behavior. a cross-sectional correlational design based on a secondary data analysis of 130 Latino parent and teenager dyads. regression and path analysis procedures were used to test seven hypotheses and the results demonstrated partial support for the model. Parent familism and knowledge about sex were significantly associated with parents' attitudes toward sexual communication with their teenagers. Parent Latino acculturation was negatively associated with parents' self-efficacy toward sexual communication with their teenagers and positevely associated with parents' subjective norms toward sexual communication with their teenagers. Teenager knowledge about sex was significantly associated with higher levels of teenagers' attitudes and subjective norms about sexual communication with parents. Only the predictor of teenagers' attitudes toward having sex in the next 3 months was significantly associated with teenagers' intentions to have sex in the next 3 months. the results of this study provide important information to guide future research that can inform development of interventions to prevent risky teenager sexual behavior among Latinos.

A Novel Genome-Information Content-Based Statistic for Genome-Wide Association Analysis Designed for Next-Generation Sequencing Data

PubMed Central

Luo, Li; Zhu, Yun

2012-01-01

Abstract The genome-wide association studies (GWAS) designed for next-generation sequencing data involve testing association of genomic variants, including common, low frequency, and rare variants. The current strategies for association studies are well developed for identifying association of common variants with the common diseases, but may be ill-suited when large amounts of allelic heterogeneity are present in sequence data. Recently, group tests that analyze their collective frequency differences between cases and controls shift the current variant-by-variant analysis paradigm for GWAS of common variants to the collective test of multiple variants in the association analysis of rare variants. However, group tests ignore differences in genetic effects among SNPs at different genomic locations. As an alternative to group tests, we developed a novel genome-information content-based statistics for testing association of the entire allele frequency spectrum of genomic variation with the diseases. To evaluate the performance of the proposed statistics, we use large-scale simulations based on whole genome low coverage pilot data in the 1000 Genomes Project to calculate the type 1 error rates and power of seven alternative statistics: a genome-information content-based statistic, the generalized T2, collapsing method, multivariate and collapsing (CMC) method, individual χ2 test, weighted-sum statistic, and variable threshold statistic. Finally, we apply the seven statistics to published resequencing dataset from ANGPTL3, ANGPTL4, ANGPTL5, and ANGPTL6 genes in the Dallas Heart Study. We report that the genome-information content-based statistic has significantly improved type 1 error rates and higher power than the other six statistics in both simulated and empirical datasets. PMID:22651812

A novel genome-information content-based statistic for genome-wide association analysis designed for next-generation sequencing data.

PubMed

Luo, Li; Zhu, Yun; Xiong, Momiao

2012-06-01

The genome-wide association studies (GWAS) designed for next-generation sequencing data involve testing association of genomic variants, including common, low frequency, and rare variants. The current strategies for association studies are well developed for identifying association of common variants with the common diseases, but may be ill-suited when large amounts of allelic heterogeneity are present in sequence data. Recently, group tests that analyze their collective frequency differences between cases and controls shift the current variant-by-variant analysis paradigm for GWAS of common variants to the collective test of multiple variants in the association analysis of rare variants. However, group tests ignore differences in genetic effects among SNPs at different genomic locations. As an alternative to group tests, we developed a novel genome-information content-based statistics for testing association of the entire allele frequency spectrum of genomic variation with the diseases. To evaluate the performance of the proposed statistics, we use large-scale simulations based on whole genome low coverage pilot data in the 1000 Genomes Project to calculate the type 1 error rates and power of seven alternative statistics: a genome-information content-based statistic, the generalized T(2), collapsing method, multivariate and collapsing (CMC) method, individual χ(2) test, weighted-sum statistic, and variable threshold statistic. Finally, we apply the seven statistics to published resequencing dataset from ANGPTL3, ANGPTL4, ANGPTL5, and ANGPTL6 genes in the Dallas Heart Study. We report that the genome-information content-based statistic has significantly improved type 1 error rates and higher power than the other six statistics in both simulated and empirical datasets.

Genome-wide pathway-based association analysis identifies risk pathways associated with Parkinson's disease.

PubMed

Zhang, Mingming; Mu, Hongbo; Shang, Zhenwei; Kang, Kai; Lv, Hongchao; Duan, Lian; Li, Jin; Chen, Xinren; Teng, Yanbo; Jiang, Yongshuai; Zhang, Ruijie

2017-01-06

Parkinson's disease (PD) is the second most common neurodegenerative disease. It is generally believed that it is influenced by both genetic and environmental factors, but the precise pathogenesis of PD is unknown to date. In this study, we performed a pathway analysis based on genome-wide association study (GWAS) to detect risk pathways of PD in three GWAS datasets. We first mapped all SNP markers to autosomal genes in each GWAS dataset. Then, we evaluated gene risk values using the minimum P-value of the tagSNPs. We took a pathway as a unit to identify the risk pathways based on the cumulative risks of the genes in the pathway. Finally, we combine the analysis results of the three datasets to detect the high risk pathways associated with PD. We found there were five same pathways in the three datasets. Besides, we also found there were five pathways which were shared in two datasets. Most of these pathways are associated with nervoussystem. Five pathways had been reported to be PD-related pathways in the previous literature. Our findings also implied that there was a close association between immune response and PD. Continued investigation of these pathways will further help us explain the pathogenesis of PD. Copyright © 2016. Published by Elsevier Ltd.

A method for gene-based pathway analysis using genomewide association study summary statistics reveals nine new type 1 diabetes associations.

PubMed

Evangelou, Marina; Smyth, Deborah J; Fortune, Mary D; Burren, Oliver S; Walker, Neil M; Guo, Hui; Onengut-Gumuscu, Suna; Chen, Wei-Min; Concannon, Patrick; Rich, Stephen S; Todd, John A; Wallace, Chris

2014-12-01

Pathway analysis can complement point-wise single nucleotide polymorphism (SNP) analysis in exploring genomewide association study (GWAS) data to identify specific disease-associated genes that can be candidate causal genes. We propose a straightforward methodology that can be used for conducting a gene-based pathway analysis using summary GWAS statistics in combination with widely available reference genotype data. We used this method to perform a gene-based pathway analysis of a type 1 diabetes (T1D) meta-analysis GWAS (of 7,514 cases and 9,045 controls). An important feature of the conducted analysis is the removal of the major histocompatibility complex gene region, the major genetic risk factor for T1D. Thirty-one of the 1,583 (2%) tested pathways were identified to be enriched for association with T1D at a 5% false discovery rate. We analyzed these 31 pathways and their genes to identify SNPs in or near these pathway genes that showed potentially novel association with T1D and attempted to replicate the association of 22 SNPs in additional samples. Replication P-values were skewed (P=9.85×10-11) with 12 of the 22 SNPs showing P<0.05. Support, including replication evidence, was obtained for nine T1D associated variants in genes ITGB7 (rs11170466, P=7.86×10-9), NRP1 (rs722988, 4.88×10-8), BAD (rs694739, 2.37×10-7), CTSB (rs1296023, 2.79×10-7), FYN (rs11964650, P=5.60×10-7), UBE2G1 (rs9906760, 5.08×10-7), MAP3K14 (rs17759555, 9.67×10-7), ITGB1 (rs1557150, 1.93×10-6), and IL7R (rs1445898, 2.76×10-6). The proposed methodology can be applied to other GWAS datasets for which only summary level data are available. © 2014 The Authors. ** Genetic Epidemiology published by Wiley Periodicals, Inc.

Extracting Cross-Ontology Weighted Association Rules from Gene Ontology Annotations.

PubMed

Agapito, Giuseppe; Milano, Marianna; Guzzi, Pietro Hiram; Cannataro, Mario

2016-01-01

Gene Ontology (GO) is a structured repository of concepts (GO Terms) that are associated to one or more gene products through a process referred to as annotation. The analysis of annotated data is an important opportunity for bioinformatics. There are different approaches of analysis, among those, the use of association rules (AR) which provides useful knowledge, discovering biologically relevant associations between terms of GO, not previously known. In a previous work, we introduced GO-WAR (Gene Ontology-based Weighted Association Rules), a methodology for extracting weighted association rules from ontology-based annotated datasets. We here adapt the GO-WAR algorithm to mine cross-ontology association rules, i.e., rules that involve GO terms present in the three sub-ontologies of GO. We conduct a deep performance evaluation of GO-WAR by mining publicly available GO annotated datasets, showing how GO-WAR outperforms current state of the art approaches.

Preprocessing and Analysis of LC-MS-Based Proteomic Data

PubMed Central

Tsai, Tsung-Heng; Wang, Minkun; Ressom, Habtom W.

2016-01-01

Liquid chromatography coupled with mass spectrometry (LC-MS) has been widely used for profiling protein expression levels. This chapter is focused on LC-MS data preprocessing, which is a crucial step in the analysis of LC-MS based proteomics. We provide a high-level overview, highlight associated challenges, and present a step-by-step example for analysis of data from LC-MS based untargeted proteomic study. Furthermore, key procedures and relevant issues with the subsequent analysis by multiple reaction monitoring (MRM) are discussed. PMID:26519169

Association between glutathione S-transferase P1 Ile (105) Val gene polymorphism and chronic obstructive pulmonary disease: A meta-analysis based on seventeen case-control studies.

PubMed

Yang, Lingjing; Li, Xixia; Tong, Xiang; Fan, Hong

2015-12-01

Previous studies have shown that glutathione S-transferase P1 (GSTP1) was associated with chronic obstructive pulmonary disease (COPD). However, the association between GSTP1 Ile (105) Val gene polymorphism and COPD remains controversial. To drive a more precise estimation, we performed a meta-analysis based on published case-control studies. An electronic search of PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated (CNKI) Database for papers on GSTP1 Ile (105) Val gene polymorphism and COPD risk was performed. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygote model, heterozygote model, dominant model, recessive model and an additive mode. Statistical heterogeneity, test of publication bias and sensitivity analysis was performed. The software STATA (Version 13.0) was used data analysis. Overall, seventeen studies with 1892 cases and 2012 controls were included in this meta-analysis. The GSTP1 Ile (105) Val polymorphism showed pooled odds ratios for the homozygote comparison (OR = 1.501, 95%CI [0.862, 2.614]), heterozygote comparison (OR = 0.924, 95%CI [0.733, 1.165]), dominant model (OR = 1.003, 95%CI [0.756, 1.331]), recessive model (OR = 1.510, 95%CI [0.934, 2.439]), and an additive model (OR = 1.072, 95%CI [0.822, 1.398]). In conclusion, the current meta-analysis, based on the most updated information, showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in any genetic models. The results of subgroup analysis also showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in Asian population and Caucasian population. Further studies involving large populations and careful control with age, sex, ethnicity, and cigarette smoking are greatly needed.

Association between glutathione S-transferase P1 Ile (105) Val gene polymorphism and chronic obstructive pulmonary disease: A meta-analysis based on seventeen case–control studies

PubMed Central

Yang, Lingjing; Li, Xixia; Tong, Xiang; Fan, Hong

2015-01-01

Introduction Previous studies have shown that glutathione S-transferase P1 (GSTP1) was associated with chronic obstructive pulmonary disease (COPD). However, the association between GSTP1 Ile (105) Val gene polymorphism and COPD remains controversial. To drive a more precise estimation, we performed a meta-analysis based on published case–control studies. Methods An electronic search of PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated (CNKI) Database for papers on GSTP1 Ile (105) Val gene polymorphism and COPD risk was performed. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygote model, heterozygote model, dominant model, recessive model and an additive mode. Statistical heterogeneity, test of publication bias and sensitivity analysis was performed. The software STATA (Version 13.0) was used data analysis. Results Overall, seventeen studies with 1892 cases and 2012 controls were included in this meta-analysis. The GSTP1 Ile (105) Val polymorphism showed pooled odds ratios for the homozygote comparison (OR = 1.501, 95%CI [0.862, 2.614]), heterozygote comparison (OR = 0.924, 95%CI [0.733, 1.165]), dominant model (OR = 1.003, 95%CI [0.756, 1.331]), recessive model (OR = 1.510, 95%CI [0.934, 2.439]), and an additive model (OR = 1.072, 95%CI [0.822, 1.398]). Conclusions In conclusion, the current meta-analysis, based on the most updated information, showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in any genetic models. The results of subgroup analysis also showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in Asian population and Caucasian population. Further studies involving large populations and careful control with age, sex, ethnicity, and cigarette smoking are greatly needed. PMID:26504746

Association analysis and marker development for grain quality traits using USDA diverse rice germplasm collections

USDA-ARS?s Scientific Manuscript database

New molecular markers are being designed and validated for grain quality improvement based on computationally assisted analysis of genome wide association study (GWAS) findings across multiple panels and multiple grain quality traits. The traits include grain dimensions, apparent amylose content (A...

High performance computing enabling exhaustive analysis of higher order single nucleotide polymorphism interaction in Genome Wide Association Studies.

PubMed

Goudey, Benjamin; Abedini, Mani; Hopper, John L; Inouye, Michael; Makalic, Enes; Schmidt, Daniel F; Wagner, John; Zhou, Zeyu; Zobel, Justin; Reumann, Matthias

2015-01-01

Genome-wide association studies (GWAS) are a common approach for systematic discovery of single nucleotide polymorphisms (SNPs) which are associated with a given disease. Univariate analysis approaches commonly employed may miss important SNP associations that only appear through multivariate analysis in complex diseases. However, multivariate SNP analysis is currently limited by its inherent computational complexity. In this work, we present a computational framework that harnesses supercomputers. Based on our results, we estimate a three-way interaction analysis on 1.1 million SNP GWAS data requiring over 5.8 years on the full "Avoca" IBM Blue Gene/Q installation at the Victorian Life Sciences Computation Initiative. This is hundreds of times faster than estimates for other CPU based methods and four times faster than runtimes estimated for GPU methods, indicating how the improvement in the level of hardware applied to interaction analysis may alter the types of analysis that can be performed. Furthermore, the same analysis would take under 3 months on the currently largest IBM Blue Gene/Q supercomputer "Sequoia" at the Lawrence Livermore National Laboratory assuming linear scaling is maintained as our results suggest. Given that the implementation used in this study can be further optimised, this runtime means it is becoming feasible to carry out exhaustive analysis of higher order interaction studies on large modern GWAS.

GAC: Gene Associations with Clinical, a web based application

PubMed Central

Zhang, Xinyan; Rupji, Manali; Kowalski, Jeanne

2018-01-01

We present GAC, a shiny R based tool for interactive visualization of clinical associations based on high-dimensional data. The tool provides a web-based suite to perform supervised principal component analysis (SuperPC), an approach that uses both high-dimensional data, such as gene expression, combined with clinical data to infer clinical associations. We extended the approach to address binary outcomes, in addition to continuous and time-to-event data in our package, thereby increasing the use and flexibility of SuperPC.  Additionally, the tool provides an interactive visualization for summarizing results based on a forest plot for both binary and time-to-event data.  In summary, the GAC suite of tools provide a one stop shop for conducting statistical analysis to identify and visualize the association between a clinical outcome of interest and high-dimensional data types, such as genomic data. Our GAC package has been implemented in R and is available via http://shinygispa.winship.emory.edu/GAC/. The developmental repository is available at https://github.com/manalirupji/GAC. PMID:29263780

Subcopula-based measure of asymmetric association for contingency tables.

PubMed

Wei, Zheng; Kim, Daeyoung

2017-10-30

For the analysis of a two-way contingency table, a new asymmetric association measure is developed. The proposed method uses the subcopula-based regression between the discrete variables to measure the asymmetric predictive powers of the variables of interest. Unlike the existing measures of asymmetric association, the subcopula-based measure is insensitive to the number of categories in a variable, and thus, the magnitude of the proposed measure can be interpreted as the degree of asymmetric association in the contingency table. The theoretical properties of the proposed subcopula-based asymmetric association measure are investigated. We illustrate the performance and advantages of the proposed measure using simulation studies and real data examples. Copyright © 2017 John Wiley & Sons, Ltd.

Gene-based rare allele analysis identified a risk gene of Alzheimer's disease.

PubMed

Kim, Jong Hun; Song, Pamela; Lim, Hyunsun; Lee, Jae-Hyung; Lee, Jun Hong; Park, Sun Ah

2014-01-01

Alzheimer's disease (AD) has a strong propensity to run in families. However, the known risk genes excluding APOE are not clinically useful. In various complex diseases, gene studies have targeted rare alleles for unsolved heritability. Our study aims to elucidate previously unknown risk genes for AD by targeting rare alleles. We used data from five publicly available genetic studies from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the database of Genotypes and Phenotypes (dbGaP). A total of 4,171 cases and 9,358 controls were included. The genotype information of rare alleles was imputed using 1,000 genomes. We performed gene-based analysis of rare alleles (minor allele frequency≤3%). The genome-wide significance level was defined as meta P<1.8×10(-6) (0.05/number of genes in human genome = 0.05/28,517). ZNF628, which is located at chromosome 19q13.42, showed a genome-wide significant association with AD. The association of ZNF628 with AD was not dependent on APOE ε4. APOE and TREM2 were also significantly associated with AD, although not at genome-wide significance levels. Other genes identified by targeting common alleles could not be replicated in our gene-based rare allele analysis. We identified that rare variants in ZNF628 are associated with AD. The protein encoded by ZNF628 is known as a transcription factor. Furthermore, the associations of APOE and TREM2 with AD were highly significant, even in gene-based rare allele analysis, which implies that further deep sequencing of these genes is required in AD heritability studies.

Antibody-Based Sensors: Principles, Problems and Potential for Detection of Pathogens and Associated Toxins

PubMed Central

Byrne, Barry; Stack, Edwina; Gilmartin, Niamh; O'Kennedy, Richard

2009-01-01

Antibody-based sensors permit the rapid and sensitive analysis of a range of pathogens and associated toxins. A critical assessment of the implementation of such formats is provided, with reference to their principles, problems and potential for ‘on-site’ analysis. Particular emphasis is placed on the detection of foodborne bacterial pathogens, such as Escherichia coli and Listeria monocytogenes, and additional examples relating to the monitoring of fungal pathogens, viruses, mycotoxins, marine toxins and parasites are also provided. PMID:22408533

Timescale analysis of rule-based biochemical reaction networks

PubMed Central

Klinke, David J.; Finley, Stacey D.

2012-01-01

The flow of information within a cell is governed by a series of protein-protein interactions that can be described as a reaction network. Mathematical models of biochemical reaction networks can be constructed by repetitively applying specific rules that define how reactants interact and what new species are formed upon reaction. To aid in understanding the underlying biochemistry, timescale analysis is one method developed to prune the size of the reaction network. In this work, we extend the methods associated with timescale analysis to reaction rules instead of the species contained within the network. To illustrate this approach, we applied timescale analysis to a simple receptor-ligand binding model and a rule-based model of Interleukin-12 (IL-12) signaling in näive CD4+ T cells. The IL-12 signaling pathway includes multiple protein-protein interactions that collectively transmit information; however, the level of mechanistic detail sufficient to capture the observed dynamics has not been justified based upon the available data. The analysis correctly predicted that reactions associated with JAK2 and TYK2 binding to their corresponding receptor exist at a pseudo-equilibrium. In contrast, reactions associated with ligand binding and receptor turnover regulate cellular response to IL-12. An empirical Bayesian approach was used to estimate the uncertainty in the timescales. This approach complements existing rank- and flux-based methods that can be used to interrogate complex reaction networks. Ultimately, timescale analysis of rule-based models is a computational tool that can be used to reveal the biochemical steps that regulate signaling dynamics. PMID:21954150

An epigenome-wide association meta-analysis of prenatal maternal stress in neonates: A model approach for replication

PubMed Central

Rijlaarsdam, Jolien; Pappa, Irene; Walton, Esther; Bakermans-Kranenburg, Marian J.; Mileva-Seitz, Viara R.; Rippe, Ralph C.A.; Roza, Sabine J.; Jaddoe, Vincent W.V.; Verhulst, Frank C.; Felix, Janine F.; Cecil, Charlotte A.M.; Relton, Caroline L.; Gaunt, Tom R.; McArdle, Wendy; Mill, Jonathan; Barker, Edward D.; Tiemeier, Henning; van IJzendoorn, Marinus H.

2016-01-01

ABSTRACT Prenatal maternal stress exposure has been associated with neonatal differential DNA methylation. However, the available evidence in humans is largely based on candidate gene methylation studies, where only a few CpG sites were evaluated. The aim of this study was to examine the association between prenatal exposure to maternal stress and offspring genome-wide cord blood methylation using different methods. First, we conducted a meta-analysis and follow-up pathway analyses. Second, we used novel region discovery methods [i.e., differentially methylated regions (DMRs) analyses]. To this end, we used data from two independent population-based studies, the Generation R Study (n = 912) and the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 828), to (i) measure genome-wide DNA methylation in cord blood and (ii) extract a prenatal maternal stress composite. The meta-analysis (ntotal = 1,740) revealed no epigenome-wide (meta P <1.00e-07) associations of prenatal maternal stress exposure with neonatal differential DNA methylation. Follow-up analyses of the top hits derived from our epigenome-wide meta-analysis (meta P <1.00e-04) indicated an over-representation of the methyltransferase activity pathway. We identified no Bonferroni-corrected (P <1.00e-06) DMRs associated with prenatal maternal stress exposure. Combining data from two independent population-based samples in an epigenome-wide meta-analysis, the current study indicates that there are no large effects of prenatal maternal stress exposure on neonatal DNA methylation. Such replication efforts are essential in the search for robust associations, whether derived from candidate gene methylation or epigenome-wide studies. PMID:26889969

An evidence base for patient-centered cancer care: a meta-analysis of studies of observed communication between cancer specialists and their patients.

PubMed

Venetis, Maria K; Robinson, Jeffrey D; Turkiewicz, Katie Laplant; Allen, Mike

2009-12-01

In the context of patients visiting cancer specialists, the objective is to test the association between both patient-centered communication (including Affective Behavior and Participation Behavior) and Instrumental Behavior and patients' post-visit satisfaction with a variety of visit phenomena. Meta-analysis of 25 articles representing 10 distinct data sets. Both patient-centered- and instrumental behavior are significantly, positively associated with satisfaction, with patient-centered communication having a relatively stronger association. There is an evidence base for the efficacy of patient-centered care. Cancer specialists need to train to improve their patient-centered communication.

HSI top-down requirements analysis for ship manpower reduction

NASA Astrophysics Data System (ADS)

Malone, Thomas B.; Bost, J. R.

2000-11-01

U.S. Navy ship acquisition programs such as DD 21 and CVNX are increasingly relying on top down requirements analysis (TDRA) to define and assess design approaches for workload and manpower reduction, and for ensuring required levels of human performance, reliability, safety, and quality of life at sea. The human systems integration (HSI) approach to TDRA begins with a function analysis which identifies the functions derived from the requirements in the Operational Requirements Document (ORD). The function analysis serves as the function baseline for the ship, and also supports the definition of RDT&E and Total Ownership Cost requirements. A mission analysis is then conducted to identify mission scenarios, again based on requirements in the ORD, and the Design Reference Mission (DRM). This is followed by a mission/function analysis which establishes the function requirements to successfully perform the ship's missions. Function requirements of major importance for HSI are information, performance, decision, and support requirements associated with each function. An allocation of functions defines the roles of humans and automation in performing the functions associated with a mission. Alternate design concepts, based on function allocation strategies, are then described, and task networks associated with the concepts are developed. Task network simulations are conducted to assess workloads and human performance capabilities associated with alternate concepts. An assessment of the affordability and risk associated with alternate concepts is performed, and manning estimates are developed for feasible design concepts.

Weighted functional linear regression models for gene-based association analysis.

PubMed

Belonogova, Nadezhda M; Svishcheva, Gulnara R; Wilson, James F; Campbell, Harry; Axenovich, Tatiana I

2018-01-01

Functional linear regression models are effectively used in gene-based association analysis of complex traits. These models combine information about individual genetic variants, taking into account their positions and reducing the influence of noise and/or observation errors. To increase the power of methods, where several differently informative components are combined, weights are introduced to give the advantage to more informative components. Allele-specific weights have been introduced to collapsing and kernel-based approaches to gene-based association analysis. Here we have for the first time introduced weights to functional linear regression models adapted for both independent and family samples. Using data simulated on the basis of GAW17 genotypes and weights defined by allele frequencies via the beta distribution, we demonstrated that type I errors correspond to declared values and that increasing the weights of causal variants allows the power of functional linear models to be increased. We applied the new method to real data on blood pressure from the ORCADES sample. Five of the six known genes with P < 0.1 in at least one analysis had lower P values with weighted models. Moreover, we found an association between diastolic blood pressure and the VMP1 gene (P = 8.18×10-6), when we used a weighted functional model. For this gene, the unweighted functional and weighted kernel-based models had P = 0.004 and 0.006, respectively. The new method has been implemented in the program package FREGAT, which is freely available at https://cran.r-project.org/web/packages/FREGAT/index.html.

A Most Probable Point-Based Method for Reliability Analysis, Sensitivity Analysis and Design Optimization

NASA Technical Reports Server (NTRS)

Hou, Gene J.-W; Newman, Perry A. (Technical Monitor)

2004-01-01

A major step in a most probable point (MPP)-based method for reliability analysis is to determine the MPP. This is usually accomplished by using an optimization search algorithm. The minimum distance associated with the MPP provides a measurement of safety probability, which can be obtained by approximate probability integration methods such as FORM or SORM. The reliability sensitivity equations are derived first in this paper, based on the derivatives of the optimal solution. Examples are provided later to demonstrate the use of these derivatives for better reliability analysis and reliability-based design optimization (RBDO).

Predictors of Word-Reading Ability in 7-Year-Olds: Analysis of Data from a U.K. Cohort Study

ERIC Educational Resources Information Center

Russell, Ginny; Ukoumunne, Obioha C.; Ryder, Denise; Golding, Jean; Norwich, Brahm

2018-01-01

Previous U.K. population-based studies have found associations amongst early speech and language difficulties, socioeconomic disadvantage and children's word-reading ability later on. We examine the strength of these associations in a recent U.K. population-based birth cohort. Analyses were based on 13,680 participants. Linear regression models…

Text mining facilitates database curation - extraction of mutation-disease associations from Bio-medical literature.

PubMed

Ravikumar, Komandur Elayavilli; Wagholikar, Kavishwar B; Li, Dingcheng; Kocher, Jean-Pierre; Liu, Hongfang

2015-06-06

Advances in the next generation sequencing technology has accelerated the pace of individualized medicine (IM), which aims to incorporate genetic/genomic information into medicine. One immediate need in interpreting sequencing data is the assembly of information about genetic variants and their corresponding associations with other entities (e.g., diseases or medications). Even with dedicated effort to capture such information in biological databases, much of this information remains 'locked' in the unstructured text of biomedical publications. There is a substantial lag between the publication and the subsequent abstraction of such information into databases. Multiple text mining systems have been developed, but most of them focus on the sentence level association extraction with performance evaluation based on gold standard text annotations specifically prepared for text mining systems. We developed and evaluated a text mining system, MutD, which extracts protein mutation-disease associations from MEDLINE abstracts by incorporating discourse level analysis, using a benchmark data set extracted from curated database records. MutD achieves an F-measure of 64.3% for reconstructing protein mutation disease associations in curated database records. Discourse level analysis component of MutD contributed to a gain of more than 10% in F-measure when compared against the sentence level association extraction. Our error analysis indicates that 23 of the 64 precision errors are true associations that were not captured by database curators and 68 of the 113 recall errors are caused by the absence of associated disease entities in the abstract. After adjusting for the defects in the curated database, the revised F-measure of MutD in association detection reaches 81.5%. Our quantitative analysis reveals that MutD can effectively extract protein mutation disease associations when benchmarking based on curated database records. The analysis also demonstrates that incorporating discourse level analysis significantly improved the performance of extracting the protein-mutation-disease association. Future work includes the extension of MutD for full text articles.

Trans-Ethnic Meta-Analysis Identifies Common and Rare Variants Associated with Hepatocyte Growth Factor Levels in the Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Larson, Nicholas B.; Berardi, Cecilia; Decker, Paul A.; Wassel, Christina L.; Kirsch, Phillip S.; Pankow, James S.; Sale, Michele M.; de Andrade, Mariza; Sicotte, Hugues; Tang, Weihong; Hanson, Naomi Q.; Tsai, Michael Y.; Taylor, Kent D.; Bielinski, Suzette J.

2015-01-01

Summary Hepatocyte growth factor (HGF) is a mesenchyme-derived pleiotropic factor that regulates cell growth, motility, mitogenesis, and morphogenesis in a variety of cells, and increased serum levels of HGF have been linked to a number of clinical and subclinical cardiovascular disease phenotypes. However, little is currently known regarding what genetic factors influence HGF levels, despite evidence of substantial genetic contributions to HGF variation. Based upon ethnicity-stratified single-variant association analysis and trans-ethnic meta-analysis of 6201 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we discovered five statistically significant common and low-frequency variants: HGF missense polymorphism rs5745687 (p.E299K) as well as four variants (rs16844364, rs4690098, rs114303452, rs3748034) within or in proximity to HGFAC. We also identified two significant ethnicity-specific gene-level associations (A1BG in African Americans; FASN in Chinese Americans) based upon low-frequency/rare variants, while meta-analysis of gene-level results identified a significant association for HGFAC. However, identified single-variant associations explained modest proportions of the total trait variation and were not significantly associated with coronary artery calcium or coronary heart disease. Our findings indicate genetic factors influencing circulating HGF levels may be complex and ethnically diverse. PMID:25998175

Error Estimates of the Ares I Computed Turbulent Ascent Longitudinal Aerodynamic Analysis

NASA Technical Reports Server (NTRS)

Abdol-Hamid, Khaled S.; Ghaffari, Farhad

2012-01-01

Numerical predictions of the longitudinal aerodynamic characteristics for the Ares I class of vehicles, along with the associated error estimate derived from an iterative convergence grid refinement, are presented. Computational results are based on an unstructured grid, Reynolds-averaged Navier-Stokes analysis. The validity of the approach to compute the associated error estimates, derived from a base grid to an extrapolated infinite-size grid, was first demonstrated on a sub-scaled wind tunnel model at representative ascent flow conditions for which the experimental data existed. Such analysis at the transonic flow conditions revealed a maximum deviation of about 23% between the computed longitudinal aerodynamic coefficients with the base grid and the measured data across the entire roll angles. This maximum deviation from the wind tunnel data was associated with the computed normal force coefficient at the transonic flow condition and was reduced to approximately 16% based on the infinite-size grid. However, all the computed aerodynamic coefficients with the base grid at the supersonic flow conditions showed a maximum deviation of only about 8% with that level being improved to approximately 5% for the infinite-size grid. The results and the error estimates based on the established procedure are also presented for the flight flow conditions.

A Protein Domain and Family Based Approach to Rare Variant Association Analysis.

PubMed

Richardson, Tom G; Shihab, Hashem A; Rivas, Manuel A; McCarthy, Mark I; Campbell, Colin; Timpson, Nicholas J; Gaunt, Tom R

2016-01-01

It has become common practice to analyse large scale sequencing data with statistical approaches based around the aggregation of rare variants within the same gene. We applied a novel approach to rare variant analysis by collapsing variants together using protein domain and family coordinates, regarded to be a more discrete definition of a biologically functional unit. Using Pfam definitions, we collapsed rare variants (Minor Allele Frequency ≤ 1%) together in three different ways 1) variants within single genomic regions which map to individual protein domains 2) variants within two individual protein domain regions which are predicted to be responsible for a protein-protein interaction 3) all variants within combined regions from multiple genes responsible for coding the same protein domain (i.e. protein families). A conventional collapsing analysis using gene coordinates was also undertaken for comparison. We used UK10K sequence data and investigated associations between regions of variants and lipid traits using the sequence kernel association test (SKAT). We observed no strong evidence of association between regions of variants based on Pfam domain definitions and lipid traits. Quantile-Quantile plots illustrated that the overall distributions of p-values from the protein domain analyses were comparable to that of a conventional gene-based approach. Deviations from this distribution suggested that collapsing by either protein domain or gene definitions may be favourable depending on the trait analysed. We have collapsed rare variants together using protein domain and family coordinates to present an alternative approach over collapsing across conventionally used gene-based regions. Although no strong evidence of association was detected in these analyses, future studies may still find value in adopting these approaches to detect previously unidentified association signals.

Applying Model Analysis to a Resource-Based Analysis of the Force and Motion Conceptual Evaluation

ERIC Educational Resources Information Center

Smith, Trevor I.; Wittmann, Michael C.; Carter, Tom

2014-01-01

Previously, we analyzed the Force and Motion Conceptual Evaluation in terms of a resources-based model that allows for clustering of questions so as to provide useful information on how students correctly or incorrectly reason about physics. In this paper, we apply model analysis to show that the associated model plots provide more information…

Tensor decomposition-based and principal-component-analysis-based unsupervised feature extraction applied to the gene expression and methylation profiles in the brains of social insects with multiple castes.

PubMed

Taguchi, Y-H

2018-05-08

Even though coexistence of multiple phenotypes sharing the same genomic background is interesting, it remains incompletely understood. Epigenomic profiles may represent key factors, with unknown contributions to the development of multiple phenotypes, and social-insect castes are a good model for elucidation of the underlying mechanisms. Nonetheless, previous studies have failed to identify genes associated with aberrant gene expression and methylation profiles because of the lack of suitable methodology that can address this problem properly. A recently proposed principal component analysis (PCA)-based and tensor decomposition (TD)-based unsupervised feature extraction (FE) can solve this problem because these two approaches can deal with gene expression and methylation profiles even when a small number of samples is available. PCA-based and TD-based unsupervised FE methods were applied to the analysis of gene expression and methylation profiles in the brains of two social insects, Polistes canadensis and Dinoponera quadriceps. Genes associated with differential expression and methylation between castes were identified, and analysis of enrichment of Gene Ontology terms confirmed reliability of the obtained sets of genes from the biological standpoint. Biologically relevant genes, shown to be associated with significant differential gene expression and methylation between castes, were identified here for the first time. The identification of these genes may help understand the mechanisms underlying epigenetic control of development of multiple phenotypes under the same genomic conditions.

A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Non-Small Cell Lung Cancer.

PubMed

Raju, G K; Gurumurthi, K; Domike, R; Kazandjian, D; Blumenthal, G; Pazdur, R; Woodcock, J

2016-12-01

Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analyses. There is much interest in quantifying regulatory approaches to benefit and risk. In this work the use of a quantitative benefit-risk analysis was applied to regulatory decision-making about new drugs to treat advanced non-small cell lung cancer (NSCLC). Benefits and risks associated with 20 US Food and Drug Administration (FDA) decisions associated with a set of candidate treatments submitted between 2003 and 2015 were analyzed. For benefit analysis, the median overall survival (OS) was used where available. When not available, OS was estimated based on overall response rate (ORR) or progression-free survival (PFS). Risks were analyzed based on magnitude (or severity) of harm and likelihood of occurrence. Additionally, a sensitivity analysis was explored to demonstrate analysis of systematic uncertainty. FDA approval decision outcomes considered were found to be consistent with the benefit-risk logic. © 2016 American Society for Clinical Pharmacology and Therapeutics.

A Path Analysis of Latino Parental, Teenager and Cultural Variables in Teenagers' Sexual Attitudes, Norms, Self-Efficacy, and Sexual Intentions1

PubMed Central

Gaioso, Vanessa Pirani; Villarruel, Antonia Maria; Wilson, Lynda Anne; Azuero, Andres; Childs, Gwendolyn Denice; Davies, Susan Lane

2015-01-01

OBJECTIVE: to test a theoretical model based on the Parent-Based Expansion of the Theory of Planned Behavior examining relation between selected parental, teenager and cultural variables and Latino teenagers' intentions to engage in sexual behavior. METHOD: a cross-sectional correlational design based on a secondary data analysis of 130 Latino parent and teenager dyads. RESULTS: regression and path analysis procedures were used to test seven hypotheses and the results demonstrated partial support for the model. Parent familism and knowledge about sex were significantly associated with parents' attitudes toward sexual communication with their teenagers. Parent Latino acculturation was negatively associated with parents' self-efficacy toward sexual communication with their teenagers and positevely associated with parents' subjective norms toward sexual communication with their teenagers. Teenager knowledge about sex was significantly associated with higher levels of teenagers' attitudes and subjective norms about sexual communication with parents. Only the predictor of teenagers' attitudes toward having sex in the next 3 months was significantly associated with teenagers' intentions to have sex in the next 3 months. CONCLUSION: the results of this study provide important information to guide future research that can inform development of interventions to prevent risky teenager sexual behavior among Latinos. PMID:26312635

Fish intake and risk of heart failure: A meta-analysis of five prospective cohort studies

PubMed Central

HOU, LI-NA; LI, FEI; ZHOU, YOU; NIE, SHI-HUAI; SU, LIANG; CHEN, PING-AN; TAN, WAN-LONG; XU, DING-LI

2012-01-01

The findings on the association between fish intake and the risk of heart failure (HF) have been inconsistent. The purpose of this study was to clarify this potential association. We searched for relevant studies in the PubMed database through January 2012 and manually reviewed references. Five independent prospective cohort studies involving 5,273 cases and 144,917 participants were included. The summary relative risk estimates (SRRE) based on the highest compared with the lowest category of fish consumption were estimated by variance-based meta-analysis. In addition, we performed sensitivity and dose-response analyses to examine the association. Overall, an absence of an association between fish intake and HF was observed (SRRE=1.00; 95% CI, 0.81–1.24). However, fried fish intake positively associated with HF (SRRE=1.40; 95% CI, 1.22–1.61). In addition, dose-response analysis of fried fish suggested that each increment of six fried fish per month corresponded to a 37% increase of HF rate (RR=1.37; 95% CI, 1.20–1.56). In conclusion, our findings suggest that there is no significant association between fish intake and risk of HF, with the exception of a possible positive correlation with individuals comsuming fried fish, based on a limited number of studies. Future studies are required to confirm these findings. PMID:23181122

A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence

PubMed Central

Spain, S L; Pedroso, I; Kadeva, N; Miller, M B; Iacono, W G; McGue, M; Stergiakouli, E; Smith, G D; Putallaz, M; Lubinski, D; Meaburn, E L; Plomin, R; Simpson, M A

2016-01-01

Although individual differences in intelligence (general cognitive ability) are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. This study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations. We therefore performed a case–control association analysis with 1409 individuals drawn from the top 0.0003 (IQ >170) of the population distribution of intelligence and 3253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina HumanExome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes. However, analyses using genome-wide similarity between unrelated individuals (genome-wide complex trait analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (s.e. 1.7%) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis. This observation is consistent with the hypothesis that rare functional alleles are more frequently detrimental than beneficial to intelligence. PMID:26239293

A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence.

PubMed

Spain, S L; Pedroso, I; Kadeva, N; Miller, M B; Iacono, W G; McGue, M; Stergiakouli, E; Davey Smith, G; Putallaz, M; Lubinski, D; Meaburn, E L; Plomin, R; Simpson, M A

2016-08-01

Although individual differences in intelligence (general cognitive ability) are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. This study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations. We therefore performed a case-control association analysis with 1409 individuals drawn from the top 0.0003 (IQ >170) of the population distribution of intelligence and 3253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina HumanExome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes. However, analyses using genome-wide similarity between unrelated individuals (genome-wide complex trait analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (s.e. 1.7%) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis. This observation is consistent with the hypothesis that rare functional alleles are more frequently detrimental than beneficial to intelligence.

GWASinlps: Nonlocal prior based iterative SNP selection tool for genome-wide association studies.

PubMed

Sanyal, Nilotpal; Lo, Min-Tzu; Kauppi, Karolina; Djurovic, Srdjan; Andreassen, Ole A; Johnson, Valen E; Chen, Chi-Hua

2018-06-19

Multiple marker analysis of the genome-wide association study (GWAS) data has gained ample attention in recent years. However, because of the ultra high-dimensionality of GWAS data, such analysis is challenging. Frequently used penalized regression methods often lead to large number of false positives, whereas Bayesian methods are computationally very expensive. Motivated to ameliorate these issues simultaneously, we consider the novel approach of using nonlocal priors in an iterative variable selection framework. We develop a variable selection method, named, iterative nonlocal prior based selection for GWAS, or GWASinlps, that combines, in an iterative variable selection framework, the computational efficiency of the screen-and-select approach based on some association learning and the parsimonious uncertainty quantification provided by the use of nonlocal priors. The hallmark of our method is the introduction of 'structured screen-and-select' strategy, that considers hierarchical screening, which is not only based on response-predictor associations, but also based on response-response associations, and concatenates variable selection within that hierarchy. Extensive simulation studies with SNPs having realistic linkage disequilibrium structures demonstrate the advantages of our computationally efficient method compared to several frequentist and Bayesian variable selection methods, in terms of true positive rate, false discovery rate, mean squared error, and effect size estimation error. Further, we provide empirical power analysis useful for study design. Finally, a real GWAS data application was considered with human height as phenotype. An R-package for implementing the GWASinlps method is available at https://cran.r-project.org/web/packages/GWASinlps/index.html. Supplementary data are available at Bioinformatics online.

Lunar base surface mission operations. Lunar Base Systems Study (LBSS) task 4.1

NASA Technical Reports Server (NTRS)

1987-01-01

The purpose was to perform an analysis of the surface operations associated with a human-tended lunar base. Specifically, the study defined surface elements and developed mission manifests for a selected base scenario, determined the nature of surface operations associated with this scenario, generated a preliminary crew extravehicular and intravehicular activity (EVA/IVA) time resource schedule for conducting the missions, and proposed concepts for utilizing remotely operated equipment to perform repetitious or hazardous surface tasks. The operations analysis was performed on a 6 year period of human-tended lunar base operation prior to permanent occupancy. The baseline scenario was derived from a modified version of the civil needs database (CNDB) scenario. This scenario emphasizes achievement of a limited set of science and exploration objectives while emplacing the minimum habitability elements required for a permanent base.

Evidence-based cancer prevention recommendations for Japanese.

PubMed

Sasazuki, S; Inoue, M; Shimazu, T; Wakai, K; Naito, M; Nagata, C; Tanaka, K; Tsuji, I; Sugawara, Y; Mizoue, T; Matsuo, K; Ito, H; Tamakoshi, A; Sawada, N; Nakayama, T; Kitamura, Y; Sadakane, A; Tsugane, S

2018-06-01

A comprehensive evidence-based cancer prevention recommendation for Japanese was developed. We evaluated the magnitude of the associations of lifestyle factors and infection with cancer through a systematic review of the literature, meta-analysis of published data, and pooled analysis of cohort studies in Japan. Then, we judged the strength of evidence based on the consistency of the associations between exposure and cancer and biological plausibility. Important factors were extracted and summarized as an evidence-based, current cancer prevention recommendation: 'Cancer Prevention Recommendation for Japanese'. The recommendation addresses six important domains related to exposure and cancer, including smoking, alcohol drinking, diet, physical activity, body weight and infection. The next step should focus on the development of effective behavior modification programs and their implementation and dissemination.

A Meta-Analysis of Genome-Wide Association Studies of Growth Differentiation Factor-15 Concentration in Blood

PubMed Central

Jiang, Jiyang; Thalamuthu, Anbupalam; Ho, Jennifer E.; Mahajan, Anubha; Ek, Weronica E.; Brown, David A.; Breit, Samuel N.; Wang, Thomas J.; Gyllensten, Ulf; Chen, Ming-Huei; Enroth, Stefan; Januzzi, James L.; Lind, Lars; Armstrong, Nicola J.; Kwok, John B.; Schofield, Peter R.; Wen, Wei; Trollor, Julian N.; Johansson, Åsa; Morris, Andrew P.; Vasan, Ramachandran S.; Sachdev, Perminder S.; Mather, Karen A.

2018-01-01

Blood levels of growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1), have been associated with various pathological processes and diseases, including cardiovascular disease and cancer. Prior studies suggest genetic factors play a role in regulating blood MIC-1/GDF-15 concentration. In the current study, we conducted the largest genome-wide association study (GWAS) to date using a sample of ∼5,400 community-based Caucasian participants, to determine the genetic variants associated with MIC-1/GDF-15 blood concentration. Conditional and joint (COJO), gene-based association, and gene-set enrichment analyses were also carried out to identify novel loci, genes, and pathways. Consistent with prior results, a locus on chromosome 19, which includes nine single nucleotide polymorphisms (SNPs) (top SNP, rs888663, p = 1.690 × 10-35), was significantly associated with blood MIC-1/GDF-15 concentration, and explained 21.47% of its variance. COJO analysis showed evidence for two independent signals within this locus. Gene-based analysis confirmed the chromosome 19 locus association and in addition, a putative locus on chromosome 1. Gene-set enrichment analyses showed that the“COPI-mediated anterograde transport” gene-set was associated with MIC-1/GDF15 blood concentration with marginal significance after FDR correction (p = 0.067). In conclusion, a locus on chromosome 19 was associated with MIC-1/GDF-15 blood concentration with genome-wide significance, with evidence for a new locus (chromosome 1). Future studies using independent cohorts are needed to confirm the observed associations especially for the chromosomes 1 locus, and to further investigate and identify the causal SNPs that contribute to MIC-1/GDF-15 levels. PMID:29628937

A Meta-Analysis of Genome-Wide Association Studies of Growth Differentiation Factor-15 Concentration in Blood.

PubMed

Jiang, Jiyang; Thalamuthu, Anbupalam; Ho, Jennifer E; Mahajan, Anubha; Ek, Weronica E; Brown, David A; Breit, Samuel N; Wang, Thomas J; Gyllensten, Ulf; Chen, Ming-Huei; Enroth, Stefan; Januzzi, James L; Lind, Lars; Armstrong, Nicola J; Kwok, John B; Schofield, Peter R; Wen, Wei; Trollor, Julian N; Johansson, Åsa; Morris, Andrew P; Vasan, Ramachandran S; Sachdev, Perminder S; Mather, Karen A

2018-01-01

Blood levels of growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1), have been associated with various pathological processes and diseases, including cardiovascular disease and cancer. Prior studies suggest genetic factors play a role in regulating blood MIC-1/GDF-15 concentration. In the current study, we conducted the largest genome-wide association study (GWAS) to date using a sample of ∼5,400 community-based Caucasian participants, to determine the genetic variants associated with MIC-1/GDF-15 blood concentration. Conditional and joint (COJO), gene-based association, and gene-set enrichment analyses were also carried out to identify novel loci, genes, and pathways. Consistent with prior results, a locus on chromosome 19, which includes nine single nucleotide polymorphisms (SNPs) (top SNP, rs888663, p = 1.690 × 10 -35 ), was significantly associated with blood MIC-1/GDF-15 concentration, and explained 21.47% of its variance. COJO analysis showed evidence for two independent signals within this locus. Gene-based analysis confirmed the chromosome 19 locus association and in addition, a putative locus on chromosome 1. Gene-set enrichment analyses showed that the"COPI-mediated anterograde transport" gene-set was associated with MIC-1/GDF15 blood concentration with marginal significance after FDR correction ( p = 0.067). In conclusion, a locus on chromosome 19 was associated with MIC-1/GDF-15 blood concentration with genome-wide significance, with evidence for a new locus (chromosome 1). Future studies using independent cohorts are needed to confirm the observed associations especially for the chromosomes 1 locus, and to further investigate and identify the causal SNPs that contribute to MIC-1/GDF-15 levels.

Sexually Transmitted Diseases and Risk Behaviors among California Farmworkers: Results from a Population-Based Survey

ERIC Educational Resources Information Center

Brammeier, Monique; Chow, Joan M.; Samuel, Michael C.; Organista, Kurt C.; Miller, Jamie; Bolan, Gail

2008-01-01

Context: The prevalence of sexually transmitted diseases and associated risk behaviors among California farmworkers is not well described. Purpose: To estimate the prevalence of sexually transmitted diseases (STDs) and associated risk behaviors among California farmworkers. Methods: Cross-sectional analysis of population-based survey data from 6…

A genome-wide association study of corneal astigmatism: The CREAM Consortium.

PubMed

Shah, Rupal L; Li, Qing; Zhao, Wanting; Tedja, Milly S; Tideman, J Willem L; Khawaja, Anthony P; Fan, Qiao; Yazar, Seyhan; Williams, Katie M; Verhoeven, Virginie J M; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J; Pärssinen, Olavi; Wedenoja, Juho; Biino, Ginevra; Concas, Maria Pina; Uitterlinden, André; Rivadeneira, Fernando; Jaddoe, Vincent W V; Hysi, Pirro G; Sim, Xueling; Tan, Nicholas; Tham, Yih-Chung; Sensaki, Sonoko; Hofman, Albert; Vingerling, Johannes R; Jonas, Jost B; Mitchell, Paul; Hammond, Christopher J; Höhn, René; Baird, Paul N; Wong, Tien-Yin; Cheng, Chinfsg-Yu; Teo, Yik Ying; Mackey, David A; Williams, Cathy; Saw, Seang-Mei; Klaver, Caroline C W; Guggenheim, Jeremy A; Bailey-Wilson, Joan E

2018-01-01

To identify genes and genetic markers associated with corneal astigmatism. A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha ( PDGFRA ) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10 -9 . No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 ( CLDN7 ), acid phosphatase 2, lysosomal ( ACP2 ), and TNF alpha-induced protein 8 like 3 ( TNFAIP8L3 ). In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7 , ACP2 , and TNFAIP8L3 , that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.

Poisson Approximation-Based Score Test for Detecting Association of Rare Variants.

PubMed

Fang, Hongyan; Zhang, Hong; Yang, Yaning

2016-07-01

Genome-wide association study (GWAS) has achieved great success in identifying genetic variants, but the nature of GWAS has determined its inherent limitations. Under the common disease rare variants (CDRV) hypothesis, the traditional association analysis methods commonly used in GWAS for common variants do not have enough power for detecting rare variants with a limited sample size. As a solution to this problem, pooling rare variants by their functions provides an efficient way for identifying susceptible genes. Rare variant typically have low frequencies of minor alleles, and the distribution of the total number of minor alleles of the rare variants can be approximated by a Poisson distribution. Based on this fact, we propose a new test method, the Poisson Approximation-based Score Test (PAST), for association analysis of rare variants. Two testing methods, namely, ePAST and mPAST, are proposed based on different strategies of pooling rare variants. Simulation results and application to the CRESCENDO cohort data show that our methods are more powerful than the existing methods. © 2016 John Wiley & Sons Ltd/University College London.

Enhanced circulating transforming growth factor beta 1 is causally associated with an increased risk of hepatocellular carcinoma: a mendelian randomization meta-analysis.

PubMed

Lu, Wei-Qun; Qiu, Ji-Liang; Huang, Zhi-Liang; Liu, Hai-Ying

2016-12-20

The aim of this study was to test the causal association between circulating transforming growth factor beta 1 (protein: TGF-β1 and coding gene: TGFB1) and hepatocellular carcinoma by choosing TGFB1 gene C-509T polymorphism as an instrument in a Mendelian randomization (MR) meta-analysis. Ten English articles were identified for analysis. Two authors independently assessed each article and abstracted relevant data. Odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) were synthesized under a random-effects model. Overall, the association of C-509T polymorphism with hepatocellular carcinoma was negative, but its association with circulating TGF-β1 was statistically significant, with a higher concentration observed in carriers of the -509TT genotype (WMD, 95% CI, P: 1.72, 0.67-2.78, 0.001) and -509TT/-509TC genotypes (WMD, 95% CI, P: 0.98, 0.43-1.53, < 0.001). In subgroup analysis, C-509T polymorphism was significantly associated with hepatocellular carcinoma in population-based studies under homozygous-genotype (OR, 95% CI, P: 1.74, 1.08-2.80, 0.023) and dominant (OR, 95% CI, P: 1.48, 1.01-2.17, 0.047) models. Further MR analysis indicated that per unit increase in circulating TGF-β1 was significantly associated with a 38% (95% CI: 1.03-4.65) and 49% (95% CI: 1.01-6.06) increased risk of hepatocellular carcinoma under homozygous-genotype and dominant models, respectively. Conclusively, based on a MR meta-analysis, our findings suggest that enhanced circulating TGF-β1 is causally associated with an increased risk of hepatocellular carcinoma.

Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder.

PubMed

de Moor, Marleen H M; van den Berg, Stéphanie M; Verweij, Karin J H; Krueger, Robert F; Luciano, Michelle; Arias Vasquez, Alejandro; Matteson, Lindsay K; Derringer, Jaime; Esko, Tõnu; Amin, Najaf; Gordon, Scott D; Hansell, Narelle K; Hart, Amy B; Seppälä, Ilkka; Huffman, Jennifer E; Konte, Bettina; Lahti, Jari; Lee, Minyoung; Miller, Mike; Nutile, Teresa; Tanaka, Toshiko; Teumer, Alexander; Viktorin, Alexander; Wedenoja, Juho; Abecasis, Goncalo R; Adkins, Daniel E; Agrawal, Arpana; Allik, Jüri; Appel, Katja; Bigdeli, Timothy B; Busonero, Fabio; Campbell, Harry; Costa, Paul T; Davey Smith, George; Davies, Gail; de Wit, Harriet; Ding, Jun; Engelhardt, Barbara E; Eriksson, Johan G; Fedko, Iryna O; Ferrucci, Luigi; Franke, Barbara; Giegling, Ina; Grucza, Richard; Hartmann, Annette M; Heath, Andrew C; Heinonen, Kati; Henders, Anjali K; Homuth, Georg; Hottenga, Jouke-Jan; Iacono, William G; Janzing, Joost; Jokela, Markus; Karlsson, Robert; Kemp, John P; Kirkpatrick, Matthew G; Latvala, Antti; Lehtimäki, Terho; Liewald, David C; Madden, Pamela A F; Magri, Chiara; Magnusson, Patrik K E; Marten, Jonathan; Maschio, Andrea; Medland, Sarah E; Mihailov, Evelin; Milaneschi, Yuri; Montgomery, Grant W; Nauck, Matthias; Ouwens, Klaasjan G; Palotie, Aarno; Pettersson, Erik; Polasek, Ozren; Qian, Yong; Pulkki-Råback, Laura; Raitakari, Olli T; Realo, Anu; Rose, Richard J; Ruggiero, Daniela; Schmidt, Carsten O; Slutske, Wendy S; Sorice, Rossella; Starr, John M; St Pourcain, Beate; Sutin, Angelina R; Timpson, Nicholas J; Trochet, Holly; Vermeulen, Sita; Vuoksimaa, Eero; Widen, Elisabeth; Wouda, Jasper; Wright, Margaret J; Zgaga, Lina; Porteous, David; Minelli, Alessandra; Palmer, Abraham A; Rujescu, Dan; Ciullo, Marina; Hayward, Caroline; Rudan, Igor; Metspalu, Andres; Kaprio, Jaakko; Deary, Ian J; Räikkönen, Katri; Wilson, James F; Keltikangas-Järvinen, Liisa; Bierut, Laura J; Hettema, John M; Grabe, Hans J; van Duijn, Cornelia M; Evans, David M; Schlessinger, David; Pedersen, Nancy L; Terracciano, Antonio; McGue, Matt; Penninx, Brenda W J H; Martin, Nicholas G; Boomsma, Dorret I

2015-07-01

Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 < P < .05) and MDD (4.02 × 10-9 < P < .05) in the 2 other cohorts. This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism.

Model Based Analysis and Test Generation for Flight Software

NASA Technical Reports Server (NTRS)

Pasareanu, Corina S.; Schumann, Johann M.; Mehlitz, Peter C.; Lowry, Mike R.; Karsai, Gabor; Nine, Harmon; Neema, Sandeep

2009-01-01

We describe a framework for model-based analysis and test case generation in the context of a heterogeneous model-based development paradigm that uses and combines Math- Works and UML 2.0 models and the associated code generation tools. This paradigm poses novel challenges to analysis and test case generation that, to the best of our knowledge, have not been addressed before. The framework is based on a common intermediate representation for different modeling formalisms and leverages and extends model checking and symbolic execution tools for model analysis and test case generation, respectively. We discuss the application of our framework to software models for a NASA flight mission.

Interleukin 1 beta gene and risk of schizophrenia: detailed case-control and family-based studies and an updated meta-analysis.

PubMed

Shibuya, Masako; Watanabe, Yuichiro; Nunokawa, Ayako; Egawa, Jun; Kaneko, Naoshi; Igeta, Hirofumi; Someya, Toshiyuki

2014-01-01

Interleukin-1 beta (IL-1β) has been implicated in the pathophysiology of schizophrenia. To assess whether the IL1B gene confers increased susceptibility to schizophrenia, we conducted case-control and family-based studies and an updated meta-analysis. We tested the association between IL1B and schizophrenia in 1229 case-control and 112 trio samples using 12 markers, including common tagging single nucleotide variations (SNVs) and a rare non-synonymous variation detected by resequencing the coding regions. We also performed a meta-analysis of rs16944 using a total of 8724 case-control and 201 trio samples from 16 independent populations. We found no significant associations between any of the 12 SNVs examined and schizophrenia in either case-control or trio samples. Moreover, our meta-analysis results showed no significant association between the common SNV, rs16944, and schizophrenia. The present study does not support a role for IL1B in schizophrenia susceptibility.

Dietary patterns and risk of colorectal adenoma: a systematic review and meta-analysis of observational studies.

PubMed

Godos, J; Bella, F; Torrisi, A; Sciacca, S; Galvano, F; Grosso, G

2016-12-01

Current evidence suggests that dietary patterns may play an important role in colorectal cancer risk. The present study aimed to perform a systematic review and meta-analysis of observational studies exploring the association between dietary patterns and colorectal adenomas (a precancerous condition). Pubmed and EMBASE electronic databases were systematically searched to retrieve eligible studies. Only studies exploring the risk or association with colorectal adenomas for the highest versus lowest category of exposure to a posteriori dietary patterns were included in the quantitative analysis. Random-effects models were applied to calculate relative risks (RRs) of colorectal adenomas for high adherence to healthy or unhealthy dietary patterns. Statistical heterogeneity and publication bias were explored. Twelve studies were reviewed. Three studies explored a priori dietary patterns using scores identifying adherence to the Mediterranean, Paleolithic and Dietary Approaches to Stop Hypertension (DASH) diet and reported an association with decreased colorectal adenoma risk. Two studies tested the association with colorectal adenomas between a posteriori dietary patterns showing lower odds of disease related to plant-based compared to meat-based dietary patterns. Seven studies identified 23 a posteriori dietary patterns and the analysis revealed that higher adherence to healthy and unhealthy dietary patterns was significantly associated risk of colorectal adenomas (RR = 0.81, 95% confidence interval = 0.71, 0.94 and RR = 1.24, 95% confidence interval = 1.13, 1.35, respectively) with no evidence of heterogeneity or publication bias. The results of this systematic review and meta-analysis indicate that dietary patterns may be associated with the risk of colorectal adenomas. © 2016 The British Dietetic Association Ltd.

GRace: a MATLAB-based application for fitting the discrimination-association model.

PubMed

Stefanutti, Luca; Vianello, Michelangelo; Anselmi, Pasquale; Robusto, Egidio

2014-10-28

The Implicit Association Test (IAT) is a computerized two-choice discrimination task in which stimuli have to be categorized as belonging to target categories or attribute categories by pressing, as quickly and accurately as possible, one of two response keys. The discrimination association model has been recently proposed for the analysis of reaction time and accuracy of an individual respondent to the IAT. The model disentangles the influences of three qualitatively different components on the responses to the IAT: stimuli discrimination, automatic association, and termination criterion. The article presents General Race (GRace), a MATLAB-based application for fitting the discrimination association model to IAT data. GRace has been developed for Windows as a standalone application. It is user-friendly and does not require any programming experience. The use of GRace is illustrated on the data of a Coca Cola-Pepsi Cola IAT, and the results of the analysis are interpreted and discussed.

Heritable DNA methylation marks associated with susceptibility to breast cancer.

PubMed

Joo, Jihoon E; Dowty, James G; Milne, Roger L; Wong, Ee Ming; Dugué, Pierre-Antoine; English, Dallas; Hopper, John L; Goldgar, David E; Giles, Graham G; Southey, Melissa C

2018-02-28

Mendelian-like inheritance of germline DNA methylation in cancer susceptibility genes has been previously reported. We aimed to scan the genome for heritable methylation marks associated with breast cancer susceptibility by studying 25 Australian multiple-case breast cancer families. Here we report genome-wide DNA methylation measured in 210 peripheral blood DNA samples provided by family members using the Infinium HumanMethylation450. We develop and apply a new statistical method to identify heritable methylation marks based on complex segregation analysis. We estimate carrier probabilities for the 1000 most heritable methylation marks based on family structure, and we use Cox proportional hazards survival analysis to identify 24 methylation marks with corresponding carrier probabilities significantly associated with breast cancer. We replicate an association with breast cancer risk for four of the 24 marks using an independent nested case-control study. Here, we report a novel approach for identifying heritable DNA methylation marks associated with breast cancer risk.

The Implication of Using NVivo Software in Qualitative Data Analysis: Evidence-Based Reflections.

PubMed

Zamawe, F C

2015-03-01

For a long time, electronic data analysis has been associated with quantitative methods. However, Computer Assisted Qualitative Data Analysis Software (CAQDAS) are increasingly being developed. Although the CAQDAS has been there for decades, very few qualitative health researchers report using it. This may be due to the difficulties that one has to go through to master the software and the misconceptions that are associated with using CAQDAS. While the issue of mastering CAQDAS has received ample attention, little has been done to address the misconceptions associated with CAQDAS. In this paper, the author reflects on his experience of interacting with one of the popular CAQDAS (NVivo) in order to provide evidence-based implications of using the software. The key message is that unlike statistical software, the main function of CAQDAS is not to analyse data but rather to aid the analysis process, which the researcher must always remain in control of. In other words, researchers must equally know that no software can analyse qualitative data. CAQDAS are basically data management packages, which support the researcher during analysis.

Genome-Wide Linkage and Regional Association Study of Blood Pressure Response to the Cold Pressor Test in Han Chinese: The GenSalt Study

PubMed Central

Yang, Xueli; Gu, Dongfeng; He, Jiang; Hixson, James E.; Rao, Dabeeru C.; Lu, Fanghong; Mu, Jianjun; Jaquish, Cashell E.; Chen, Jing; Huang, Jianfeng; Shimmin, Lawrence C.; Rice, Treva K.; Chen, Jichun; Wu, Xigui; Liu, Depei; Kelly, Tanika N.

2014-01-01

Background Blood pressure (BP) response to cold pressor test (CPT) is associated with increased risk of cardiovascular disease. We performed a genome-wide linkage scan and regional association analysis to identify genetic determinants of BP response to CPT. Methods and Results A total of 1,961 Chinese participants completed the CPT. Multipoint quantitative trait linkage analysis was performed, followed by single-marker and gene-based analyses of variants in promising linkage regions (logarithm of odds, LOD ≥ 2). A suggestive linkage signal was identified for systolic BP (SBP) response to CPT at 20p13-20p12.3, with a maximum multipoint LOD score of 2.37. Based on regional association analysis with 1,351 SNPs in the linkage region, we found that marker rs2326373 at 20p13 was significantly associated with mean arterial pressure (MAP) responses to CPT (P = 8.8×10−6) after FDR adjustment for multiple comparisons. A similar trend was also observed for SBP response (P = 0.03) and DBP response (P = 4.6×10−5). Results of gene-based analyses showed that variants in genes MCM8 and SLC23A2 were associated with SBP response to CPT (P = 4.0×10−5 and 2.7×10−4, respectively), and variants in genes MCM8 and STK35 were associated with MAP response to CPT (P = 1.5×10−5 and 5.0×10−5, respectively). Conclusions Within a suggestive linkage region on chromosome 20, we identified a novel variant associated with BP responses to CPT. We also found gene-based associations of MCM8, SLC23A2 and STK35 in this region. Further work is warranted to confirm these findings. Clinical Trial Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT00721721. PMID:25028485

Factors associated with pharyngeal carriage of Neisseria meningitidis among Israel Defense Force personnel at the end of their compulsory service.

PubMed

Block, C; Gdalevich, M; Buber, R; Ashkenazi, I; Ashkenazi, S; Keller, N

1999-02-01

In this 1 year cross-sectional study of personnel being discharged from compulsory military service, an available database of health-related information was used to examine the association of meningococcal carriage with socio-demographic factors. A representative, systematic sample of 1632 personnel was interviewed and had throat cultures taken. The overall meningococcal carriage rate was 16%. Serogroups B and Y accounted for 76% and 13% of the isolates respectively. In univariate analysis, carriage was associated with male gender (P < 0.0001), < 12 years school education (P = 0.002), smoking (P = 0.014), and service at a 'closed' base, reflecting greater interpersonal contact (P < 0.0001). In multivariate analysis, only service on a closed base and male gender retained significance. School education of < 12 years remained significant for females only. Variables not associated with carriage included number of siblings, intensity of smoking, and use of the contraceptive pill. In this setting, meningococcal carriage was associated with the type of base on which soldiers served; and smoking was not an independent risk factor for carriage.

Power System Transient Stability Based on Data Mining Theory

NASA Astrophysics Data System (ADS)

Cui, Zhen; Shi, Jia; Wu, Runsheng; Lu, Dan; Cui, Mingde

2018-01-01

In order to study the stability of power system, a power system transient stability based on data mining theory is designed. By introducing association rules analysis in data mining theory, an association classification method for transient stability assessment is presented. A mathematical model of transient stability assessment based on data mining technology is established. Meanwhile, combining rule reasoning with classification prediction, the method of association classification is proposed to perform transient stability assessment. The transient stability index is used to identify the samples that cannot be correctly classified in association classification. Then, according to the critical stability of each sample, the time domain simulation method is used to determine the state, so as to ensure the accuracy of the final results. The results show that this stability assessment system can improve the speed of operation under the premise that the analysis result is completely correct, and the improved algorithm can find out the inherent relation between the change of power system operation mode and the change of transient stability degree.

A Cost-Based Analysis on Using DoD Civilian Workforce to Perform Ordnance Support in Pearl Harbor

DTIC Science & Technology

study examines whether using the government civilian workforce to perform ordnance handling generates cost savings when compared with contracting...Using a cost-based analysis, this study reviews all the associated costs of converting to a government civilian workforce and compares them with the cost

Temperament Profiles from Infancy to Middle Childhood: Development and Associations with Behavior Problems

ERIC Educational Resources Information Center

Janson, Harald; Mathiesen, Kristin S.

2008-01-01

The authors applied I-States as Objects Analysis (ISOA), a recently proposed person-oriented analytic approach, to the study of temperament development in 921 Norwegian children from a population-based sample. A 5-profile classification based on cluster analysis of standardized mother reports of activity, sociability, emotionality, and shyness at…

An Analysis of Losses to the Southern Commercial Timberland Base

Treesearch

Ian A. Munn; David Cleaves

1998-01-01

Demographic and physical factors influencing the conversion of commercial timberland iu the south to non-forestry uses between the last two Forest Inventory Analysis (FIA) surveys were investigated. GIS techniques linked Census data and FIA plot level data. Multinomial logit regression identified factors associated with losses to the timberland base. Conversion to...

Kernel-Based Measure of Variable Importance for Genetic Association Studies.

PubMed

Gallego, Vicente; Luz Calle, M; Oller, Ramon

2017-06-17

The identification of genetic variants that are associated with disease risk is an important goal of genetic association studies. Standard approaches perform univariate analysis where each genetic variant, usually Single Nucleotide Polymorphisms (SNPs), is tested for association with disease status. Though many genetic variants have been identified and validated so far using this univariate approach, for most complex diseases a large part of their genetic component is still unknown, the so called missing heritability. We propose a Kernel-based measure of variable importance (KVI) that provides the contribution of a SNP, or a group of SNPs, to the joint genetic effect of a set of genetic variants. KVI can be used for ranking genetic markers individually, sets of markers that form blocks of linkage disequilibrium or sets of genetic variants that lie in a gene or a genetic pathway. We prove that, unlike the univariate analysis, KVI captures the relationship with other genetic variants in the analysis, even when measured at the individual level for each genetic variable separately. This is specially relevant and powerful for detecting genetic interactions. We illustrate the results with data from an Alzheimer's disease study and show through simulations that the rankings based on KVI improve those rankings based on two measures of importance provided by the Random Forest. We also prove with a simulation study that KVI is very powerful for detecting genetic interactions.

Calibration-free concentration analysis for an analyte prone to self-association.

PubMed

Imamura, Hiroshi; Honda, Shinya

2017-01-01

Calibration-free concentration analysis (CFCA) based on surface plasmon resonance uses the diffusion coefficient of an analyte to determine the concentration of that analyte in a bulk solution. In general, CFCA is avoided when investigating analytes prone to self-association, as the heterogeneous diffusion coefficient results in a loss of precision. The derivation for self-association of the analyte was presented here. By using the diffusion coefficient for the monomeric state, CFCA provides the lowest possible concentration even though the analyte is self-associated. Copyright © 2016 Elsevier Inc. All rights reserved.

Integrating sentiment analysis and term associations with geo-temporal visualizations on customer feedback streams

NASA Astrophysics Data System (ADS)

Hao, Ming; Rohrdantz, Christian; Janetzko, Halldór; Keim, Daniel; Dayal, Umeshwar; Haug, Lars-Erik; Hsu, Mei-Chun

2012-01-01

Twitter currently receives over 190 million tweets (small text-based Web posts) and manufacturing companies receive over 10 thousand web product surveys a day, in which people share their thoughts regarding a wide range of products and their features. A large number of tweets and customer surveys include opinions about products and services. However, with Twitter being a relatively new phenomenon, these tweets are underutilized as a source for determining customer sentiments. To explore high-volume customer feedback streams, we integrate three time series-based visual analysis techniques: (1) feature-based sentiment analysis that extracts, measures, and maps customer feedback; (2) a novel idea of term associations that identify attributes, verbs, and adjectives frequently occurring together; and (3) new pixel cell-based sentiment calendars, geo-temporal map visualizations and self-organizing maps to identify co-occurring and influential opinions. We have combined these techniques into a well-fitted solution for an effective analysis of large customer feedback streams such as for movie reviews (e.g., Kung-Fu Panda) or web surveys (buyers).

Genome-wide association analysis based on multiple imputation with low-depth GBS data: application to biofuel traits in reed canarygrass

USDA-ARS?s Scientific Manuscript database

Genotyping-by-sequencing allows for large-scale genetic analyses in plant species with no reference genome, creating the challenge of sound inference in the presence of uncertain genotypes. Here we report an imputation-based genome-wide association study (GWAS) in reed canarygrass (Phalaris arundina...

Player Preferences and Social Harm: An Analysis of the Relationships between Player Characteristics, Gambling Modes, and Problem Gambling

ERIC Educational Resources Information Center

Young, Martin; Stevens, Matthew

2009-01-01

To explore the structure of gambling participation and its association with problem gambling, we draw upon Caillois's distinction between games based on competition (i.e. "agon") and those based on chance (i.e. "alea"). The idea that "alea" and "agon" are socially patterned and associated with differing…

Association of adiponectin promoter variants with traits and clusters of metabolic syndrome in Arabs: family-based study.

PubMed

Zadjali, F; Al-Yahyaee, S; Hassan, M O; Albarwani, S; Bayoumi, R A

2013-09-25

Plasma levels of adiponectin are decreased in type 2 diabetes, obesity and hypertension. Our aim was to use a family-based analysis to identify the genetic variants of the adiponectin (ADIPOQ) gene that are associated with obesity, insulin resistance, dyslipidemia and hypertension, among Arabs. We screened 328 Arabs in one large extended family for single nucleotide polymorphisms (SNPs) in the promoter region of the ADIPOQ gene. Two common SNPs were detected: rs17300539 and rs266729. Evidences of association between traits related to the metabolic syndrome and the SNPs were studied by implementing quantitative genetic association analysis. Results showed that SNP rs266729 was significantly associated with body weight (p-value=0.001), waist circumference (p-value=0.037), BMI (p-value=0.015) and percentage of total body fat (p-value=0.003). Up to 4.1% of heritability of obesity traits was explained by the rs266729 locus. Further cross-sectional analysis showed that carriers of the G allele had significantly higher values of waist circumference, BMI and percentage of total body fat (p-values 0.014, 0.004 and 0.032, respectively). No association was detected between SNP rs266729 and other clusters of metabolic syndrome or their traits except for HOMA-IR and fasting plasma insulin levels, p-values 0.035 and 0.004, respectively. In contrast, both measured genotype and cross-sectional analysis failed to detect an association between the SNP rs17300539 with traits and clusters of metabolic syndrome. In conclusion, we showed family-based evidence of association of SNP rs266729 at ADIPOQ gene with traits defining obesity in Arab population. This is important for future prediction and prevention of obesity in population where obesity is in an increasing trend. © 2013 Elsevier B.V. All rights reserved.

Does the impact of a plant-based diet during pregnancy on birth weight differ by ethnicity? A dietary pattern analysis from a prospective Canadian birth cohort alliance

PubMed Central

de Souza, Russell J; Shaikh, Mateen; Desai, Dipika; Lefebvre, Diana L; Gupta, Milan; Wilson, Julie; Wahi, Gita; Subbarao, Padmaja; Becker, Allan B; Mandhane, Piush; Turvey, Stuart E; Beyene, Joseph; Atkinson, Stephanie; Morrison, Katherine M; McDonald, Sarah; Teo, Koon K; Sears, Malcolm R; Anand, Sonia S

2017-01-01

Objective Birth weight is an indicator of newborn health and a strong predictor of health outcomes in later life. Significant variation in diet during pregnancy between ethnic groups in high-income countries provides an ideal opportunity to investigate the influence of maternal diet on birth weight. Setting Four multiethnic birth cohorts based in Canada (the NutriGen Alliance). Participants 3997 full-term mother–infant pairs of diverse ethnic groups who had principal component analysis-derived diet pattern scores—plant-based, Western and health-conscious—and birth weight data. Results No associations were identified between the Western and health-conscious diet patterns and birth weight; however, the plant-based dietary pattern was inversely associated with birth weight (β=−67.6 g per 1-unit increase; P<0.001), and an interaction with non-white ethnicity and birth weight was observed. Ethnically stratified analyses demonstrated that among white Europeans, maternal consumption of a plant-based diet associated with lower birth weight (β=−65.9 g per 1-unit increase; P<0.001), increased risk of small-for-gestational age (SGA; OR=1.46; 95% CI 1.08 to 1.54;P=0.005) and reduced risk of large-for-gestational age (LGA; OR=0.71; 95% CI 0.53 to 0.95;P=0.02). Among South Asians, maternal consumption of a plant-based diet associated with a higher birth weight (β=+40.5 g per 1-unit increase; P=0.01), partially explained by cooked vegetable consumption. Conclusions Maternal consumption of a plant-based diet during pregnancy is associated with birth weight. Among white Europeans, a plant-based diet is associated with lower birth weight, reduced odds of an infant born LGA and increased odds of SGA, whereas among South Asians living in Canada, a plant-based diet is associated with increased birth weight. PMID:29138203

Socio-Economic Status and Prevalence of Self-Reported Osteoporosis in Tehran: Results from a Large Population-Based Cross-Sectional Study (Urban HEART-2).

PubMed

Asadi-Lari, M; Salimi, Y; Vaez-Mahdavi, M R; Faghihzadeh, S; Haeri Mehrizi, A A; Jorjoran Shushtari, Z; Cheraghian, Bahman

2018-04-10

Osteoporosis is a widespread disease among older peoples. The aim of this study is to estimate the prevalence of self-reported osteoporosis and assessing its association with socio-economic status. A population-based cross-sectional study was conducted in Tehran, Iran in 2011. Participants were 45,990 individuals aged above 20 years from 22 urban districts. Osteoporosis was measured by self-administrative questionnaire. Wealth index was constructed using principal component analysis based on household assets. Chi-square test, chi square test for trend, and crude odds ratio were used to assess associations in univariate analysis. Multiple logistic regression utilized to estimate adjusted associations between self-reported osteoporosis and socio-economic status.The overall estimated prevalence of self-reported osteoporosis was 4% (95% CI 3.88-4.13), 1.19% in men, and 6.84% in women (P < 0.001). The prevalence increased considerably as age increased (P for trend < 0.001). In multivariable analysis, education and wealth status were negative, and smoking was positively associated with the prevalence of self-reported osteoporosis. No association was found between participants' skill levels and Townsend deprivation index with the prevalence of self-reported osteoporosis.The findings of the present study have improved understanding of the association between socioeconomic status and osteoporosis in the Iranian population. It is important to consider socioeconomic status in screening and prevention programs.

Genome-wide linkage and association analysis of cardiometabolic phenotypes in Hispanic Americans.

PubMed

Hellwege, Jacklyn N; Palmer, Nicholette D; Dimitrov, Latchezar; Keaton, Jacob M; Tabb, Keri L; Sajuthi, Satria; Taylor, Kent D; Ng, Maggie C Y; Speliotes, Elizabeth K; Hawkins, Gregory A; Long, Jirong; Ida Chen, Yii-Der; Lorenzo, Carlos; Norris, Jill M; Rotter, Jerome I; Langefeld, Carl D; Wagenknecht, Lynne E; Bowden, Donald W

2017-02-01

Linkage studies of complex genetic diseases have been largely replaced by genome-wide association studies, due in part to limited success in complex trait discovery. However, recent interest in rare and low-frequency variants motivates re-examination of family-based methods. In this study, we investigated the performance of two-point linkage analysis for over 1.6 million single-nucleotide polymorphisms (SNPs) combined with single variant association analysis to identify high impact variants, which are both strongly linked and associated with cardiometabolic traits in up to 1414 Hispanics from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Evaluation of all 50 phenotypes yielded 83 557 000 LOD (logarithm of the odds) scores, with 9214 LOD scores ⩾3.0, 845 ⩾4.0 and 89 ⩾5.0, with a maximal LOD score of 6.49 (rs12956744 in the LAMA1 gene for tumor necrosis factor-α (TNFα) receptor 2). Twenty-seven variants were associated with P<0.005 as well as having an LOD score >4, including variants in the NFIB gene under a linkage peak with TNFα receptor 2 levels on chromosome 9. Linkage regions of interest included a broad peak (31 Mb) on chromosome 1q with acute insulin response (max LOD=5.37). This region was previously documented with type 2 diabetes in family-based studies, providing support for the validity of these results. Overall, we have demonstrated the utility of two-point linkage and association in comprehensive genome-wide array-based SNP genotypes.

Separate class true discovery rate degree of association sets for biomarker identification.

PubMed

Crager, Michael R; Ahmed, Murat

2014-01-01

In 2008, Efron showed that biological features in a high-dimensional study can be divided into classes and a separate false discovery rate (FDR) analysis can be conducted in each class using information from the entire set of features to assess the FDR within each class. We apply this separate class approach to true discovery rate degree of association (TDRDA) set analysis, which is used in clinical-genomic studies to identify sets of biomarkers having strong association with clinical outcome or state while controlling the FDR. Careful choice of classes based on prior information can increase the identification power of the separate class analysis relative to the overall analysis.

Solution of quadratic matrix equations for free vibration analysis of structures.

NASA Technical Reports Server (NTRS)

Gupta, K. K.

1973-01-01

An efficient digital computer procedure and the related numerical algorithm are presented herein for the solution of quadratic matrix equations associated with free vibration analysis of structures. Such a procedure enables accurate and economical analysis of natural frequencies and associated modes of discretized structures. The numerically stable algorithm is based on the Sturm sequence method, which fully exploits the banded form of associated stiffness and mass matrices. The related computer program written in FORTRAN V for the JPL UNIVAC 1108 computer proves to be substantially more accurate and economical than other existing procedures of such analysis. Numerical examples are presented for two structures - a cantilever beam and a semicircular arch.

metaCCA: summary statistics-based multivariate meta-analysis of genome-wide association studies using canonical correlation analysis.

PubMed

Cichonska, Anna; Rousu, Juho; Marttinen, Pekka; Kangas, Antti J; Soininen, Pasi; Lehtimäki, Terho; Raitakari, Olli T; Järvelin, Marjo-Riitta; Salomaa, Veikko; Ala-Korpela, Mika; Ripatti, Samuli; Pirinen, Matti

2016-07-01

A dominant approach to genetic association studies is to perform univariate tests between genotype-phenotype pairs. However, analyzing related traits together increases statistical power, and certain complex associations become detectable only when several variants are tested jointly. Currently, modest sample sizes of individual cohorts, and restricted availability of individual-level genotype-phenotype data across the cohorts limit conducting multivariate tests. We introduce metaCCA, a computational framework for summary statistics-based analysis of a single or multiple studies that allows multivariate representation of both genotype and phenotype. It extends the statistical technique of canonical correlation analysis to the setting where original individual-level records are not available, and employs a covariance shrinkage algorithm to achieve robustness.Multivariate meta-analysis of two Finnish studies of nuclear magnetic resonance metabolomics by metaCCA, using standard univariate output from the program SNPTEST, shows an excellent agreement with the pooled individual-level analysis of original data. Motivated by strong multivariate signals in the lipid genes tested, we envision that multivariate association testing using metaCCA has a great potential to provide novel insights from already published summary statistics from high-throughput phenotyping technologies. Code is available at https://github.com/aalto-ics-kepaco anna.cichonska@helsinki.fi or matti.pirinen@helsinki.fi Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

metaCCA: summary statistics-based multivariate meta-analysis of genome-wide association studies using canonical correlation analysis

PubMed Central

Cichonska, Anna; Rousu, Juho; Marttinen, Pekka; Kangas, Antti J.; Soininen, Pasi; Lehtimäki, Terho; Raitakari, Olli T.; Järvelin, Marjo-Riitta; Salomaa, Veikko; Ala-Korpela, Mika; Ripatti, Samuli; Pirinen, Matti

2016-01-01

Motivation: A dominant approach to genetic association studies is to perform univariate tests between genotype-phenotype pairs. However, analyzing related traits together increases statistical power, and certain complex associations become detectable only when several variants are tested jointly. Currently, modest sample sizes of individual cohorts, and restricted availability of individual-level genotype-phenotype data across the cohorts limit conducting multivariate tests. Results: We introduce metaCCA, a computational framework for summary statistics-based analysis of a single or multiple studies that allows multivariate representation of both genotype and phenotype. It extends the statistical technique of canonical correlation analysis to the setting where original individual-level records are not available, and employs a covariance shrinkage algorithm to achieve robustness. Multivariate meta-analysis of two Finnish studies of nuclear magnetic resonance metabolomics by metaCCA, using standard univariate output from the program SNPTEST, shows an excellent agreement with the pooled individual-level analysis of original data. Motivated by strong multivariate signals in the lipid genes tested, we envision that multivariate association testing using metaCCA has a great potential to provide novel insights from already published summary statistics from high-throughput phenotyping technologies. Availability and implementation: Code is available at https://github.com/aalto-ics-kepaco Contacts: anna.cichonska@helsinki.fi or matti.pirinen@helsinki.fi Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153689

Gene- and pathway-based association tests for multiple traits with GWAS summary statistics.

PubMed

Kwak, Il-Youp; Pan, Wei

2017-01-01

To identify novel genetic variants associated with complex traits and to shed new insights on underlying biology, in addition to the most popular single SNP-single trait association analysis, it would be useful to explore multiple correlated (intermediate) traits at the gene- or pathway-level by mining existing single GWAS or meta-analyzed GWAS data. For this purpose, we present an adaptive gene-based test and a pathway-based test for association analysis of multiple traits with GWAS summary statistics. The proposed tests are adaptive at both the SNP- and trait-levels; that is, they account for possibly varying association patterns (e.g. signal sparsity levels) across SNPs and traits, thus maintaining high power across a wide range of situations. Furthermore, the proposed methods are general: they can be applied to mixed types of traits, and to Z-statistics or P-values as summary statistics obtained from either a single GWAS or a meta-analysis of multiple GWAS. Our numerical studies with simulated and real data demonstrated the promising performance of the proposed methods. The methods are implemented in R package aSPU, freely and publicly available at: https://cran.r-project.org/web/packages/aSPU/ CONTACT: weip@biostat.umn.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Correlates of home and neighbourhood-based physical activity in UK 3-4-year-old children.

PubMed

Hnatiuk, Jill A; Hesketh, Kathryn R; van Sluijs, Esther M F

2016-12-01

Identifying context-specific correlates of home- and neighbourhood-based physical activity in preschool-aged children may help improve intervention program development for these settings. A total of 153 3-4-year-old children were recruited through preschool settings in Cambridgeshire (January-July 2013). Children wore Actiheart accelerometers for ≤7 days to assess their sedentary time (ST), light-(LPA) and moderate- to vigorous-intensity physical activity (MVPA). A parent-completed questionnaire assessed correlates across the ecological model and the child's preschool attendance during the measurement week. Only accelerometer data for times when children were at home were used. Multilevel models (Level 1: days; Level 2: child) examined associations between maternal-reported exposure variables and each outcome (children's home- and neighbourhood-based ST, LPA and MVPA) (main analysis). Further analyses included the subsample of children with complete paternal correlates data (father analysis). In the main analyses, children with older siblings engaged in less ST. Children whose mothers reported being 'moderately inactive' or 'active' (vs. inactive) engaged in less LPA, while children whose mothers worked >35 h week -1 engaged in less MVPA. More equipment at home was associated with lower LPA but greater MVPA. In the father analysis, father's television viewing before 6 pm was associated with greater ST and less MVPA in children; the negative association between mother's activity and children's LPA was retained. Family demographics and parental behaviours appear to have the strongest association with children's home- and neighbourhood-based ST, LPA and MVPA. This study further highlights the importance of examining both maternal and paternal behaviours. © The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association.

Exome Array Analysis of Nuclear Lens Opacity.

PubMed

Loomis, Stephanie J; Klein, Alison P; Lee, Kristine E; Chen, Fei; Bomotti, Samantha; Truitt, Barbara; Iyengar, Sudha K; Klein, Ronald; Klein, Barbara E K; Duggal, Priya

2018-06-01

Nuclear cataract is the most common subtype of age-related cataract, the leading cause of blindness worldwide. It results from advanced nuclear sclerosis, or opacity in the center of the optic lens, and is affected by both genetic and environmental risk factors, including smoking. We sought to understand the genetic factors associated with nuclear sclerosis through interrogation of rare and low frequency coding variants using exome array data. We analyzed Illumina Human Exome Array data for 1,488 participants of European ancestry in the Beaver Dam Eye Study who were without cataract surgery for association with nuclear sclerosis grade, controlling for age and sex. We performed single-variant regression analysis for 32,138 variants with minor allele frequency (MAF) ≥0.003. In addition, gene-based analysis of 11,844 genes containing at least two variants with MAF < 0.05 was performed using a gene-based unified burden and non-burden sequence kernel association test (SKAT-O). Additionally, both single-variant and gene-based analyses were analyzed stratified by smoking status. No single-variant test was statistically significant after Bonferroni correction (p < 1.6 × 10 -6 ; top single nucleotide polymorphism (SNP): rs144458991, p = 2.83 × 10 -5 ). Gene-based tests were suggestively associated with the gene RNF149 overall (p = 8.29 × 10 -6 ) and among never smokers (N = 790, p = 2.67 × 10 -6 ). This study did not find a significant genetic association with nuclear sclerosis, the possible association with the RNF149 gene highlights a potential candidate gene for future studies that aim to understand the genetic architecture of nuclear sclerosis.

Variants in TTC25 affect autistic trait in patients with autism spectrum disorder and general population.

PubMed

Vojinovic, Dina; Brison, Nathalie; Ahmad, Shahzad; Noens, Ilse; Pappa, Irene; Karssen, Lennart C; Tiemeier, Henning; van Duijn, Cornelia M; Peeters, Hilde; Amin, Najaf

2017-08-01

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder with a complex genetic architecture. To identify genetic variants underlying ASD, we performed single-variant and gene-based genome-wide association studies using a dense genotyping array containing over 2.3 million single-nucleotide variants in a discovery sample of 160 families with at least one child affected with non-syndromic ASD using a binary (ASD yes/no) phenotype and a quantitative autistic trait. Replication of the top findings was performed in Psychiatric Genomics Consortium and Erasmus Rucphen Family (ERF) cohort study. Significant association of quantitative autistic trait was observed with the TTC25 gene at 17q21.2 (effect size=10.2, P-value=3.4 × 10 -7 ) in the gene-based analysis. The gene also showed nominally significant association in the cohort-based ERF study (effect=1.75, P-value=0.05). Meta-analysis of discovery and replication improved the association signal (P-value meta =1.5 × 10 -8 ). No genome-wide significant signal was observed in the single-variant analysis of either the binary ASD phenotype or the quantitative autistic trait. Our study has identified a novel gene TTC25 to be associated with quantitative autistic trait in patients with ASD. The replication of association in a cohort-based study and the effect estimate suggest that variants in TTC25 may also be relevant for broader ASD phenotype in the general population. TTC25 is overexpressed in frontal cortex and testis and is known to be involved in cilium movement and thus an interesting candidate gene for autistic trait.

What can time-frequency and phase coherence measures tell us about the genetic basis of P3 amplitude?

PubMed Central

McGue, Matt; Iacono, William G.

2017-01-01

In a recent comprehensive investigation, we largely failed to identify significant genetic markers associated with P3 amplitude or to corroborate previous associations between P3 and specific single nucleotide polymorphisms (SNPs) or genes. In the present study we extended this line of investigation to examine time-frequency (TF) activity and intertrial phase coherence (ITPC) in the P3 time window, both of which are associated with P3 amplitude. Previous genome-wide research has reported associations between P3-related theta and delta activity and individual genetic variants. A large, population-based sample of 4211 subjects, comprising male and female adolescent twins and their parents, was genotyped for 527,828 single nucleotide polymorphisms (SNPs), from which over six million SNPs were accurately imputed. Heritability estimates were greater for TF energy than ITPC, whether based on biometric models or the combined influence of all measured SNPs (derived from genome-wide complex trait analysis). The magnitude of overlap in the specific SNPs associated with delta energy and ITPC and P3 amplitude was significant. A genome-wide analysis of all SNPs, accompanied by an analysis of approximately 17,600 genes, indicated a region of chromosome 2 around TEKT4 that was significantly associated with theta ITPC. Analysis of candidate SNPs and genes previously reported to be associated with P3 or related phenotypes yielded one association surviving correction for multiple tests: between theta energy and CRHR1. However, we did not obtain significant associations for SNPs implicated in previous genome-wide studies of TF measures. Identifying specific genetic variants associated with P3 amplitude remains a challenge. PMID:27871913

Childhood autism spectrum disorders and exposure to nitrogen dioxide, and particulate matter air pollution: A review and meta-analysis.

PubMed

Flores-Pajot, Marie-Claire; Ofner, Marianna; Do, Minh T; Lavigne, Eric; Villeneuve, Paul J

2016-11-01

Genetic and environmental factors have been recognized to play an important role in autism. The possibility that exposure to outdoor air pollution increases the risk of autism spectrum disorder (ASD) has been an emerging area of research. Herein, we present a systematic review, and meta-analysis of published epidemiological studies that have investigated these associations. We undertook a comprehensive search strategy to identify studies that investigated outdoor air pollution and autism in children. Overall, seven cohorts and five case-control studies met our inclusion criteria for the meta-analysis. We summarized the associations between exposure to air pollution and ASD based on the following critical exposure windows: (i) first, second and third trimester of pregnancy, (ii) entire pregnancy, and (iii) postnatal period. Random effects meta-analysis modeling was undertaken to derive pooled risk estimates for these exposures across the studies. The meta-estimates for the change in ASD associated with a 10μg/m 3 increase in exposure in PM 2.5 and 10 ppb increase in NO 2 during pregnancy were 1.34 (95% CI:0.83, 2.17) and 1.05 (95% CI:0.99, 1.11), respectively. Stronger associations were observed for exposures received after birth, but these estimates were unstable as they were based on only two studies. O 3 exposure was weakly associated with ASD during the third trimester of pregnancy and during the entire pregnancy, however, these estimates were also based on only two studies. Our meta-analysis support the hypothesis that exposure to ambient air pollution is associated with an increased risk of autism. Our findings should be interpreted cautiously due to relatively small number of studies, and several studies were unable to control for other key risk factors. Copyright © 2016 Elsevier Inc. All rights reserved.

Neighborhood social capital is associated with participation in health checks of a general population: a multilevel analysis of a population-based lifestyle intervention- the Inter99 study.

PubMed

Bender, Anne Mette; Kawachi, Ichiro; Jørgensen, Torben; Pisinger, Charlotta

2015-07-22

Participation in population-based preventive health check has declined over the past decades. More research is needed to determine factors enhancing participation. The objective of this study was to examine the association between two measures of neighborhood level social capital on participation in the health check phase of a population-based lifestyle intervention. The study population comprised 12,568 residents of 73 Danish neighborhoods in the intervention group of a large population-based lifestyle intervention study - the Inter99. Two measures of social capital were applied; informal socializing and voting turnout. In a multilevel analysis only adjusting for age and sex, a higher level of neighborhood social capital was associated with higher probability of participating in the health check. Inclusion of both individual socioeconomic position and neighborhood deprivation in the model attenuated the coefficients for informal socializing, while voting turnout became non-significant. Higher level of neighborhood social capital was associated with higher probability of participating in the health check phase of a population-based lifestyle intervention. Most of the association between neighborhood social capital and participation in preventive health checks can be explained by differences in individual socioeconomic position and level of neighborhood deprivation. Nonetheless, there seems to be some residual association between social capital and health check participation, suggesting that activating social relations in the community may be an avenue for boosting participation rates in population-based health checks. ClinicalTrials.gov (registration no. NCT00289237 ).

DCL System Research Using Advanced Approaches for Land-based or Ship-based Real-Time Recognition and Localization of Marine Mammals

DTIC Science & Technology

2012-09-30

recognition. Algorithm design and statistical analysis and feature analysis. Post -Doctoral Associate, Cornell University, Bioacoustics Research...short. The HPC-ADA was designed based on fielded systems [1-4, 6] that offer a variety of desirable attributes, specifically dynamic resource...The software package was designed to utilize parallel and distributed processing for running recognition and other advanced algorithms. DeLMA

Preparation of Forest Inventory and Analysis (FIA) and State Soil Geographic Data Base (STATSGO) data for global change research in the Eastern United States

Treesearch

Loius R. Iverson; Anantha M. G. Prasad; Charles T. Scott

1996-01-01

The USDA Forest Service's Forest Inventory and Analysis (FIA) and the Natural Resource Conservation Service's State Soil Geographic (STATSGO) data bases provide valuable natural resource data that can be analyzed at the national scale. When coupled with other data (e.g., climate), these data bases can provide insights into factors associated with current and...

Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.

PubMed

Vasan, Ramachandran S; Glazer, Nicole L; Felix, Janine F; Lieb, Wolfgang; Wild, Philipp S; Felix, Stephan B; Watzinger, Norbert; Larson, Martin G; Smith, Nicholas L; Dehghan, Abbas; Grosshennig, Anika; Schillert, Arne; Teumer, Alexander; Schmidt, Reinhold; Kathiresan, Sekar; Lumley, Thomas; Aulchenko, Yurii S; König, Inke R; Zeller, Tanja; Homuth, Georg; Struchalin, Maksim; Aragam, Jayashri; Bis, Joshua C; Rivadeneira, Fernando; Erdmann, Jeanette; Schnabel, Renate B; Dörr, Marcus; Zweiker, Robert; Lind, Lars; Rodeheffer, Richard J; Greiser, Karin Halina; Levy, Daniel; Haritunians, Talin; Deckers, Jaap W; Stritzke, Jan; Lackner, Karl J; Völker, Uwe; Ingelsson, Erik; Kullo, Iftikhar; Haerting, Johannes; O'Donnell, Christopher J; Heckbert, Susan R; Stricker, Bruno H; Ziegler, Andreas; Reffelmann, Thorsten; Redfield, Margaret M; Werdan, Karl; Mitchell, Gary F; Rice, Kenneth; Arnett, Donna K; Hofman, Albert; Gottdiener, John S; Uitterlinden, Andre G; Meitinger, Thomas; Blettner, Maria; Friedrich, Nele; Wang, Thomas J; Psaty, Bruce M; van Duijn, Cornelia M; Wichmann, H-Erich; Munzel, Thomas F; Kroemer, Heyo K; Benjamin, Emelia J; Rotter, Jerome I; Witteman, Jacqueline C; Schunkert, Heribert; Schmidt, Helena; Völzke, Henry; Blankenberg, Stefan

2009-07-08

Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.

Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms

PubMed Central

Esplin, M Sean; Manuck, Tracy A.; Varner, Michael W.; Christensen, Bryce; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Huang, Hao; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John

2015-01-01

Objective We sought to employ an innovative tool based on common biological pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB), in order to enhance investigators' ability to identify to highlight common mechanisms and underlying genetic factors responsible for SPTB. Study Design A secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks gestation. Each woman was assessed for the presence of underlying SPTB etiologies. A hierarchical cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis using VEGAS software. Results 1028 women with SPTB were assigned phenotypes. Hierarchical clustering of the phenotypes revealed five major clusters. Cluster 1 (N=445) was characterized by maternal stress, cluster 2 (N=294) by premature membrane rupture, cluster 3 (N=120) by familial factors, and cluster 4 (N=63) by maternal comorbidities. Cluster 5 (N=106) was multifactorial, characterized by infection (INF), decidual hemorrhage (DH) and placental dysfunction (PD). These three phenotypes were highly correlated by Chi-square analysis [PD and DH (p<2.2e-6); PD and INF (p=6.2e-10); INF and DH (p=0.0036)]. Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. Conclusion We identified 5 major clusters of SPTB based on a phenotype tool and hierarchal clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors underlying SPTB. PMID:26070700

Time Spent Walking and Risk of Diabetes in Japanese Adults: The Japan Public Health Center-Based Prospective Diabetes Study.

PubMed

Kabeya, Yusuke; Goto, Atsushi; Kato, Masayuki; Matsushita, Yumi; Takahashi, Yoshihiko; Isogawa, Akihiro; Inoue, Manami; Mizoue, Tetsuya; Tsugane, Shoichiro; Kadowaki, Takashi; Noda, Mitsuhiko

2016-01-01

The association between time spent walking and risk of diabetes was investigated in a Japanese population-based cohort. Data from the Japan Public Health Center-based Prospective Diabetes cohort were analyzed. The surveys of diabetes were performed at baseline and at the 5-year follow-up. Time spent walking per day was assessed using a self-reported questionnaire (<30 minutes, 30 minutes to <1 hour, 1 to <2 hours, or ≥2 hours). A cross-sectional analysis was performed among 26 488 adults in the baseline survey. Logistic regression was used to examine the association between time spent walking and the presence of unrecognized diabetes. We then performed a longitudinal analysis that was restricted to 11 101 non-diabetic adults who participated in both the baseline and 5-year surveys. The association between time spent walking and the incidence of diabetes during the 5 years was examined. In the cross-sectional analysis, 1058 participants had unrecognized diabetes. Those with time spent walking of <30 minutes per day had increased odds of having diabetes in relation to those with time spent walking of ≥2 hours (adjusted odds ratio [OR] 1.23; 95% CI, 1.02-1.48). In the longitudinal analysis, 612 participants developed diabetes during the 5 years of follow-up. However, a significant association between time spent walking and the incidence of diabetes was not observed. Increased risk of diabetes was implied in those with time spent walking of <30 minutes per day, although the longitudinal analysis failed to show a significant result.

A Model-Based Joint Identification of Differentially Expressed Genes and Phenotype-Associated Genes

PubMed Central

Seo, Minseok; Shin, Su-kyung; Kwon, Eun-Young; Kim, Sung-Eun; Bae, Yun-Jung; Lee, Seungyeoun; Sung, Mi-Kyung; Choi, Myung-Sook; Park, Taesung

2016-01-01

Over the last decade, many analytical methods and tools have been developed for microarray data. The detection of differentially expressed genes (DEGs) among different treatment groups is often a primary purpose of microarray data analysis. In addition, association studies investigating the relationship between genes and a phenotype of interest such as survival time are also popular in microarray data analysis. Phenotype association analysis provides a list of phenotype-associated genes (PAGs). However, it is sometimes necessary to identify genes that are both DEGs and PAGs. We consider the joint identification of DEGs and PAGs in microarray data analyses. The first approach we used was a naïve approach that detects DEGs and PAGs separately and then identifies the genes in an intersection of the list of PAGs and DEGs. The second approach we considered was a hierarchical approach that detects DEGs first and then chooses PAGs from among the DEGs or vice versa. In this study, we propose a new model-based approach for the joint identification of DEGs and PAGs. Unlike the previous two-step approaches, the proposed method identifies genes simultaneously that are DEGs and PAGs. This method uses standard regression models but adopts different null hypothesis from ordinary regression models, which allows us to perform joint identification in one-step. The proposed model-based methods were evaluated using experimental data and simulation studies. The proposed methods were used to analyze a microarray experiment in which the main interest lies in detecting genes that are both DEGs and PAGs, where DEGs are identified between two diet groups and PAGs are associated with four phenotypes reflecting the expression of leptin, adiponectin, insulin-like growth factor 1, and insulin. Model-based approaches provided a larger number of genes, which are both DEGs and PAGs, than other methods. Simulation studies showed that they have more power than other methods. Through analysis of data from experimental microarrays and simulation studies, the proposed model-based approach was shown to provide a more powerful result than the naïve approach and the hierarchical approach. Since our approach is model-based, it is very flexible and can easily handle different types of covariates. PMID:26964035

Association analysis of whole genome sequencing data accounting for longitudinal and family designs.

PubMed

Hu, Yijuan; Hui, Qin; Sun, Yan V

2014-01-01

Using the whole genome sequencing data and the simulated longitudinal phenotypes for 849 pedigree-based individuals from Genetic Analysis Workshop 18, we investigated various approaches to detecting the association of rare and common variants with blood pressure traits. We compared three strategies for longitudinal data: (a) using the baseline measurement only, (b) using the average from multiple visits, and (c) using all individual measurements. We also compared the power of using all of the pedigree-based data and the unrelated subset. The analyses were performed without knowledge of the underlying simulating model.

Predictors of exercise capacity following exercise-based rehabilitation in patients with coronary heart disease and heart failure: A meta-regression analysis.

PubMed

Uddin, Jamal; Zwisler, Ann-Dorthe; Lewinter, Christian; Moniruzzaman, Mohammad; Lund, Ken; Tang, Lars H; Taylor, Rod S

2016-05-01

The aim of this study was to undertake a comprehensive assessment of the patient, intervention and trial-level factors that may predict exercise capacity following exercise-based rehabilitation in patients with coronary heart disease and heart failure. Meta-analysis and meta-regression analysis. Randomized controlled trials of exercise-based rehabilitation were identified from three published systematic reviews. Exercise capacity was pooled across trials using random effects meta-analysis, and meta-regression used to examine the association between exercise capacity and a range of patient (e.g. age), intervention (e.g. exercise frequency) and trial (e.g. risk of bias) factors. 55 trials (61 exercise-control comparisons, 7553 patients) were included. Following exercise-based rehabilitation compared to control, overall exercise capacity was on average 0.95 (95% CI: 0.76-1.41) standard deviation units higher, and in trials reporting maximum oxygen uptake (VO2max) was 3.3 ml/kg.min(-1) (95% CI: 2.6-4.0) higher. There was evidence of a high level of statistical heterogeneity across trials (I(2) statistic > 50%). In multivariable meta-regression analysis, only exercise intervention intensity was found to be significantly associated with VO2max (P = 0.04); those trials with the highest average exercise intensity had the largest mean post-rehabilitation VO2max compared to control. We found considerable heterogeneity across randomized controlled trials in the magnitude of improvement in exercise capacity following exercise-based rehabilitation compared to control among patients with coronary heart disease or heart failure. Whilst higher exercise intensities were associated with a greater level of post-rehabilitation exercise capacity, there was no strong evidence to support other intervention, patient or trial factors to be predictive. © The European Society of Cardiology 2015.

Lifetime use of illicit drugs and associated factors among Brazilian schoolchildren, National Adolescent School-based Health Survey (PeNSE 2012).

PubMed

Horta, Rogério Lessa; Horta, Bernardo Lessa; da Costa, Andre Wallace Nery; do Prado, Rogério Ruscitto; Oliveira-Campos, Maryane; Malta, Deborah Carvalho

2014-01-01

This study aimed at describing the prevalence of illicit drug use among 9th grade students in the morning period of public and private schools in Brazil, and assessing associated factors. The Brazilian survey PeNSE (National Adolescent School-based Health Survey) 2012 evaluated a representative sample of 9th grade students in the morning period, in Brazil and its five regions. The use of illicit drugs at least once in life was assessed for the most commonly used drugs, such as marijuana, cocaine, crack, solvent-based glue, general ether-based inhalants, ecstasy and oxy. Data were subjected to descriptive analysis, and Pearson's χ² test and logistic regression was used in the multivariate analysis. The use of illicit drugs at least once in life was reported by 7.3% (95%CI 5.3 - 9.4) of the respondents. Logistic regression was used for multivariate analysis and the evidences suggest that illicit drug use is associated to social conditions of greater consumption power, the use of alcohol and tobacco, behaviors related to socialization, such as having friends or sexual activity, and also the perception of loneliness, loose contact between school and parents and experiences of abuse in the family environment. The outcome was inversely associated with close contact with parents and parental supervision. In addition to the association with the processes of socialization and consumption, the influence of family and school is expressed in a particularly protective manner in different records of direct supervision and care.

SimHap GUI: an intuitive graphical user interface for genetic association analysis.

PubMed

Carter, Kim W; McCaskie, Pamela A; Palmer, Lyle J

2008-12-25

Researchers wishing to conduct genetic association analysis involving single nucleotide polymorphisms (SNPs) or haplotypes are often confronted with the lack of user-friendly graphical analysis tools, requiring sophisticated statistical and informatics expertise to perform relatively straightforward tasks. Tools, such as the SimHap package for the R statistics language, provide the necessary statistical operations to conduct sophisticated genetic analysis, but lacks a graphical user interface that allows anyone but a professional statistician to effectively utilise the tool. We have developed SimHap GUI, a cross-platform integrated graphical analysis tool for conducting epidemiological, single SNP and haplotype-based association analysis. SimHap GUI features a novel workflow interface that guides the user through each logical step of the analysis process, making it accessible to both novice and advanced users. This tool provides a seamless interface to the SimHap R package, while providing enhanced functionality such as sophisticated data checking, automated data conversion, and real-time estimations of haplotype simulation progress. SimHap GUI provides a novel, easy-to-use, cross-platform solution for conducting a range of genetic and non-genetic association analyses. This provides a free alternative to commercial statistics packages that is specifically designed for genetic association analysis.

A generalized association test based on U statistics.

PubMed

Wei, Changshuai; Lu, Qing

2017-07-01

Second generation sequencing technologies are being increasingly used for genetic association studies, where the main research interest is to identify sets of genetic variants that contribute to various phenotypes. The phenotype can be univariate disease status, multivariate responses and even high-dimensional outcomes. Considering the genotype and phenotype as two complex objects, this also poses a general statistical problem of testing association between complex objects. We here proposed a similarity-based test, generalized similarity U (GSU), that can test the association between complex objects. We first studied the theoretical properties of the test in a general setting and then focused on the application of the test to sequencing association studies. Based on theoretical analysis, we proposed to use Laplacian Kernel-based similarity for GSU to boost power and enhance robustness. Through simulation, we found that GSU did have advantages over existing methods in terms of power and robustness. We further performed a whole genome sequencing (WGS) scan for Alzherimer's disease neuroimaging initiative data, identifying three genes, APOE , APOC1 and TOMM40 , associated with imaging phenotype. We developed a C ++ package for analysis of WGS data using GSU. The source codes can be downloaded at https://github.com/changshuaiwei/gsu . weichangshuai@gmail.com ; qlu@epi.msu.edu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Association of mRNA expression of TP53 and the TP53 codon 72 Arg/Pro gene polymorphism with colorectal cancer risk in Asian population: a bioinformatics analysis and meta-analysis.

PubMed

Dong, Zhiyong; Zheng, Longzhi; Liu, Weimin; Wang, Cunchuan

2018-01-01

The relationship between TP53 codon 72 Pro/Arg gene polymorphism and colorectal cancer risk in Asians is still controversial, and this bioinformatics analysis and meta-analysis was performed to assess the associations. The association studies were identified from PubMed, and eligible reports were included. RevMan 5.3.1 software, Oncolnc, cBioPortal, and Oncomine online tools were used for statistical analysis. A random/fixed effects model was used in meta-analysis. The data were reported as risk ratios or mean differences with corresponding 95% CI. We confirmed that TP53 was associated with colorectal cancer, the alteration frequency of TP53 was 53% mutation and 7% deep deletion, and TP53 mRNA expression was different in different types of colorectal cancer based on The Cancer Genome Atlas database. Then, 18 studies were included that examine the association of TP53 codon 72 gene polymorphism with colorectal cancer risk in Asians. The meta-analysis indicated that TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asian population, but Arg/Arg genotype was not (Pro allele: odds ratios [OR]=1.20, 95% CI: 1.06 to 1.35, P =0.003; Pro/Pro genotype: OR=1.39, 95% CI: 1.15 to 1.69, P =0.0007; Arg/Arg genotype: OR=0.86, 95% CI: 0.74 to 1.00, P =0.05). Interestingly, in the meta-analysis of the controls from the population-based studies, we found that TP53 codon 72 Pro/Arg gene polymorphism was associated with colorectal cancer risk (Pro allele: OR=1.33, 95% CI: 1.15 to 1.55, P =0.0002; Pro/Pro genotype: OR=1.61, 95% CI: 1.28 to 2.02, P <0.0001; Arg/Arg genotype: OR=0.77, 95% CI: 0.63 to 0.93, P =0.009). TP53 was associated with colorectal cancer, but the different value levels of mRNA expression were not associated with survival rate of colon and rectal cancer. TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asians.

Association of mRNA expression of TP53 and the TP53 codon 72 Arg/Pro gene polymorphism with colorectal cancer risk in Asian population: a bioinformatics analysis and meta-analysis

PubMed Central

Liu, Weimin; Wang, Cunchuan

2018-01-01

Background The relationship between TP53 codon 72 Pro/Arg gene polymorphism and colorectal cancer risk in Asians is still controversial, and this bioinformatics analysis and meta-analysis was performed to assess the associations. Methods The association studies were identified from PubMed, and eligible reports were included. RevMan 5.3.1 software, Oncolnc, cBioPortal, and Oncomine online tools were used for statistical analysis. A random/fixed effects model was used in meta-analysis. The data were reported as risk ratios or mean differences with corresponding 95% CI. Results We confirmed that TP53 was associated with colorectal cancer, the alteration frequency of TP53 was 53% mutation and 7% deep deletion, and TP53 mRNA expression was different in different types of colorectal cancer based on The Cancer Genome Atlas database. Then, 18 studies were included that examine the association of TP53 codon 72 gene polymorphism with colorectal cancer risk in Asians. The meta-analysis indicated that TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asian population, but Arg/Arg genotype was not (Pro allele: odds ratios [OR]=1.20, 95% CI: 1.06 to 1.35, P=0.003; Pro/Pro genotype: OR=1.39, 95% CI: 1.15 to 1.69, P=0.0007; Arg/Arg genotype: OR=0.86, 95% CI: 0.74 to 1.00, P=0.05). Interestingly, in the meta-analysis of the controls from the population-based studies, we found that TP53 codon 72 Pro/Arg gene polymorphism was associated with colorectal cancer risk (Pro allele: OR=1.33, 95% CI: 1.15 to 1.55, P=0.0002; Pro/Pro genotype: OR=1.61, 95% CI: 1.28 to 2.02, P<0.0001; Arg/Arg genotype: OR=0.77, 95% CI: 0.63 to 0.93, P=0.009). Conclusion TP53 was associated with colorectal cancer, but the different value levels of mRNA expression were not associated with survival rate of colon and rectal cancer. TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asians. PMID:29872345

The association between maternal smoking and placenta abruption: a meta-analysis.

PubMed

Shobeiri, Fatemeh; Masoumi, Seyedeh Zahra; Jenabi, Ensiyeh

2017-08-01

Several epidemiological studies have determined that maternal smoking can increase the risk of placenta abruption. To date, only a meta-analysis has been performed for assessing the relationship between smoking and placenta abruption. This meta-analysis was conducted to estimate the association between smoking and the risk of placenta abruption. A literature search was conducted in major databases such as PubMed, Web of Science, and Scopus from the earliest possible year to April 2016. The heterogeneity across studies was explored by Q-test and I 2 statistic. The publication bias was assessed using Begg's and Egger's tests. The results were reported using odds ratio (OR) estimate with its 95% confidence intervals (CI) using a random effects model. The literature search yielded 1167 publications until April 2016 with 4 309 610 participants. Based on OR estimates obtained from case-control and cohort studies, there was a significant association between smoking and placenta abruption (1.80; 95% CI: 1.75, 1.85). Based on the results of cohort studies, smoking and placenta abruption had a significant association (relative risk ratio: 1.65; 95% CI: 1.51, 1.80). Based on reports in epidemiological studies, we showed that smoking is a risk factor for placenta abruption.

Ancestry-based stratified analysis of Immunochip data identifies novel associations with celiac disease.

PubMed

Garcia-Etxebarria, Koldo; Jauregi-Miguel, Amaia; Romero-Garmendia, Irati; Plaza-Izurieta, Leticia; Legarda, Maria; Irastorza, Iñaki; Bilbao, Jose Ramon

2016-12-01

To identify candidate genes in celiac disease (CD), we reanalyzed the whole Immunochip CD cohort using a different approach that clusters individuals based on immunoancestry prior to disease association analysis, rather than by geographical origin. We detected 636 new associated SNPs (P<7.02 × 10 -07 ) and identified 5 novel genomic regions, extended 8 others previously identified and also detected 18 isolated signals defined by one or very few significant SNPs. To test whether we could identify putative candidate genes, we performed expression analyses of several genes from the top novel region (chr2:134533564-136169524), from a previously identified locus that is now extended, and a gene marked by an isolated SNP, in duodenum biopsies of active and treated CD patients, and non-celiac controls. In the largest novel region, CCNT2 and R3HDM1 were constitutively underexpressed in disease, even after gluten removal. Moreover, several genes within this region were coexpressed in patients, but not in controls. Other novel genes like KIF21B, REL and SORD also showed altered expression in active disease. Apart from the identification of novel CD loci, these results suggest that ancestry-based stratified analysis is an efficient strategy for association studies in complex diseases.

Riparian Vegetation Base-line Analysis and Monitoring Along Bishop Creek, California

Treesearch

Janet L. Nachlinger; Carl A. Fox; Patricia A. Moen

1989-01-01

A base-line analysis and long-term monitoring study of the riparian system along California's Bishop Creek is being conducted to measure the effects that planned increases in streamflow may have on riparian vegetation and associated wildlife. Six sites located in different major physiographic valley types have been selected for study. Biotic, climatologic,...

A Comparative Analysis of New Governance Instruments in the Transnational Educational Space: A Shift to Knowledge-Based Instruments?

ERIC Educational Resources Information Center

Ioannidou, Alexandra

2007-01-01

In recent years, the ongoing development towards a knowledge-based society--associated with globalization, an aging population, new technologies and organizational changes--has led to a more intensive analysis of education and learning throughout life with regard to quantitative, qualitative and financial aspects. In this framework, education…

Association of N-acetyltransferase 1 polymorphism and bladder cancer risk: an updated meta-analysis and trial sequential analysis.

PubMed

Xu, Zicheng; Li, Xiao; Qin, Zhiqiang; Xue, Jianxin; Wang, Jingyuan; Liu, Zhentao; Cai, Hongzhou; Yu, Bin; Xu, Ting; Zou, Qin

2017-07-24

Individual studies of the association between N-acetyltransferase 1 (NAT1)*10 allele and bladder cancer susceptibility have shown inconclusive results. To derive a more precise estimation of any such relationship, we performed this systemic review and updated meta-analysis based on 17 publications. A total of 17 studies were investigated with 4,322 bladder cancer cases and 4,944 controls. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Subgroup analyses were conducted based on ethnicity, sex, source of controls and detecting methods. Then trial sequential analysis was performed to evaluate whether the evidence of the results was sufficient and reduce the risk of type I error. There was no association between NAT1*10 allele and bladder cancer risk in a random-effects model (OR = 0.96, 95% CI, 0.84-1.10) or in a fixed-effects model (OR = 0.95, 95% CI, 0.87-1.03). In addition, no significantly increased risk of bladder cancer was found in any other subgroup analysis. Then, trial sequential analyses demonstrated that the results of our study need to be further verified. Despite its limitations, the results of the present meta-analysis suggested that there was no association between NAT1*10 allele and bladder cancer risk. More importantly, our findings need to be further validated regarding whether being without the NAT1*10 allele could in the future be shown to be a potential marker for the risk of bladder cancer.

Genome-wide scan in Hispanics highlights candidate loci for brain white matter hyperintensities

PubMed Central

Beecham, Ashley; Dong, Chuanhui; Wright, Clinton B.; Dueker, Nicole; Brickman, Adam M.; Wang, Liyong; DeCarli, Charles; Blanton, Susan H.; Rundek, Tatjana; Mayeux, Richard

2017-01-01

Objective: To investigate genetic variants influencing white matter hyperintensities (WMHs) in the understudied Hispanic population. Methods: Using 6.8 million single nucleotide polymorphisms (SNPs), we conducted a genome-wide association study (GWAS) to identify SNPs associated with WMH volume (WMHV) in 922 Hispanics who underwent brain MRI as a cross-section of 2 community-based cohorts in the Northern Manhattan Study and the Washington Heights–Inwood Columbia Aging Project. Multiple linear modeling with PLINK was performed to examine the additive genetic effects on ln(WMHV) after controlling for age, sex, total intracranial volume, and principal components of ancestry. Gene-based tests of association were performed using VEGAS. Replication was performed in independent samples of Europeans, African Americans, and Asians. Results: From the SNP analysis, a total of 17 independent SNPs in 7 genes had suggestive evidence of association with WMHV in Hispanics (p < 1 × 10−5) and 5 genes from the gene-based analysis with p < 1 × 10−3. One SNP (rs9957475 in GATA6) and 1 gene (UBE2C) demonstrated evidence of association (p < 0.05) in the African American sample. Four SNPs with p < 1 × 10−5 were shown to affect binding of SPI1 using RegulomeDB. Conclusions: This GWAS of 2 community-based Hispanic cohorts revealed several novel WMH-associated genetic variants. Further replication is needed in independent Hispanic samples to validate these suggestive associations, and fine mapping is needed to pinpoint causal variants. PMID:28975155

The association between physical activity and social isolation in community-dwelling older adults.

PubMed

Robins, Lauren M; Hill, Keith D; Finch, Caroline F; Clemson, Lindy; Haines, Terry

2018-02-01

Social isolation is an increasing concern in older community-dwelling adults. There is growing need to determine effective interventions addressing social isolation. This study aimed to determine whether a relationship exists between physical activity (recreational and/or household-based) and social isolation. An examination was conducted for whether group- or home-based falls prevention exercise was associated with social isolation. Cross-sectional analysis of telephone survey data was used to investigate relationships between physical activity, health, age, gender, living arrangements, ethnicity and participation in group- or home-based falls prevention exercise on social isolation. Univariable and multivariable ordered logistic regression analyses were conducted. Factors found to be significantly associated with reduced social isolation in multivariable analysis included living with a partner/spouse, reporting better general health, higher levels of household-based physical activity (OR = 1.03, CI = 1.01-1.05) and feeling less downhearted/depressed. Being more socially isolated was associated with symptoms of depression and a diagnosis of congestive heart failure (pseudo R 2 = 0.104). Findings suggest that household-based physical activity is related to social isolation in community-dwelling older adults. Further research is required to determine the nature of this relationship and to investigate the impact of group physical activity interventions on social isolation.

EXPLORING FUNCTIONAL CONNECTIVITY IN FMRI VIA CLUSTERING.

PubMed

Venkataraman, Archana; Van Dijk, Koene R A; Buckner, Randy L; Golland, Polina

2009-04-01

In this paper we investigate the use of data driven clustering methods for functional connectivity analysis in fMRI. In particular, we consider the K-Means and Spectral Clustering algorithms as alternatives to the commonly used Seed-Based Analysis. To enable clustering of the entire brain volume, we use the Nyström Method to approximate the necessary spectral decompositions. We apply K-Means, Spectral Clustering and Seed-Based Analysis to resting-state fMRI data collected from 45 healthy young adults. Without placing any a priori constraints, both clustering methods yield partitions that are associated with brain systems previously identified via Seed-Based Analysis. Our empirical results suggest that clustering provides a valuable tool for functional connectivity analysis.

Assessing the Use of Employment Screening for Sexual Assault Prevention

DTIC Science & Technology

2017-01-01

designed to address. For example, one meta-analysis found the average validity coefficient, or association, between integrity tests and job performance...or a more-general trait), and the group that is tested . For example, one meta-analysis found stronger associations between integrity tests and self... Tests Overt and personality-based integrity tests use questions designed to address somewhat different but overlapping content areas ( Ones

Analysis of a p53 Mutation Associated with Cancer Susceptibility for Biochemistry and Genetic Laboratory Courses

ERIC Educational Resources Information Center

Soto-Cruz, Isabel; Legorreta-Herrera, Martha

2009-01-01

We have devised and implemented a module for an upper division undergraduate laboratory based on the amplification and analysis of a p53 polymorphism associated with cancer susceptibility. First, students collected a drop of peripheral blood cells using a sterile sting and then used FTA cards to extract the genomic DNA. The p53 region is then PCR…

Thermal stress analysis of reusable surface insulation for shuttle

NASA Technical Reports Server (NTRS)

Ojalvo, I. U.; Levy, A.; Austin, F.

1974-01-01

An iterative procedure for accurately determining tile stresses associated with static mechanical and thermally induced internal loads is presented. The necessary conditions for convergence of the method are derived. An user-oriented computer program based upon the present method of analysis was developed. The program is capable of analyzing multi-tiled panels and determining the associated stresses. Typical numerical results from this computer program are presented.

A novel approach to select differential pathways associated with hypertrophic cardiomyopathy based on gene co‑expression analysis.

PubMed

Chen, Xiao-Min; Feng, Ming-Jun; Shen, Cai-Jie; He, Bin; Du, Xian-Feng; Yu, Yi-Bo; Liu, Jing; Chu, Hui-Min

2017-07-01

The present study was designed to develop a novel method for identifying significant pathways associated with human hypertrophic cardiomyopathy (HCM), based on gene co‑expression analysis. The microarray dataset associated with HCM (E‑GEOD‑36961) was obtained from the European Molecular Biology Laboratory‑European Bioinformatics Institute database. Informative pathways were selected based on the Reactome pathway database and screening treatments. An empirical Bayes method was utilized to construct co‑expression networks for informative pathways, and a weight value was assigned to each pathway. Differential pathways were extracted based on weight threshold, which was calculated using a random model. In order to assess whether the co‑expression method was feasible, it was compared with traditional pathway enrichment analysis of differentially expressed genes, which were identified using the significance analysis of microarrays package. A total of 1,074 informative pathways were screened out for subsequent investigations and their weight values were also obtained. According to the threshold of weight value of 0.01057, 447 differential pathways, including folding of actin by chaperonin containing T‑complex protein 1 (CCT)/T‑complex protein 1 ring complex (TRiC), purine ribonucleoside monophosphate biosynthesis and ubiquinol biosynthesis, were obtained. Compared with traditional pathway enrichment analysis, the number of pathways obtained from the co‑expression approach was increased. The results of the present study demonstrated that this method may be useful to predict marker pathways for HCM. The pathways of folding of actin by CCT/TRiC and purine ribonucleoside monophosphate biosynthesis may provide evidence of the underlying molecular mechanisms of HCM, and offer novel therapeutic directions for HCM.

Red and processed meat consumption and risk of glioma in adults: A systematic review and meta-analysis of observational studies

PubMed Central

Saneei, Parvane; Willett, Walter; Esmaillzadeh, Ahmad

2015-01-01

Background: These findings from several observational studies, investigated the association between red meat consumption and gliomas, were inconsistent. We conducted a systematic review and meta-analysis of observational studies to summarize available date on the relation between meat intake and risk of glioma. Materials and Methods: A systematic literature search of relevant reports published until May 2014 of the PubMed/Medline, ISI Web of Knowledge, Excerpta Medica database, Ovid database, Google Scholar, and Scopus databases was conducted. From 723 articles yielded in the preliminary literature search, data from eighteen publications (14 case-control, three cohort, and one nested case-control study) on unprocessed red meat, processed meat, and/or total red meat consumption in relation to glioma in adults were included in the analysis. Quality assessment of studies was performed. Random effects model was used to conduct the meta-analysis. Results: We found a positive significant association between unprocessed red meat intake and risk of glioma (relative risk [RR] = 1.30; 95% confidence interval [CI]: 1.08-1.58) after excluding three studies with uncertain type of brain cancer. This analysis included only one cohort study which revealed no relation between unprocessed red meat intake and glioma (RR = 1.75; 95% CI: 0.35-8.77). Consumption of processed meats was not related to increased risk of glioma in population-based case-control studies (RR = 1.26; 95% CI: 1.05-1.51) and reduced risk in hospital-based case-controls (RR = 0.79; 95% CI: 0.65-0.97). No significant association was seen between processed red meat intake and risk of glioma in cohort studies (RR: 1.08; 95% CI: 0.84-1.37). Total red meat consumption was not associated with risk of adult glioma in case-control or cohort studies. Conclusion: In this meta-analysis of 18 observational studies, we found a modest positive association between unprocessed red meat intake and risk of gliomas based almost entirely on case-control studies. Processed red meat was overall not associated with risk of gliomas in case-control or cohort studies. PMID:26600837

Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

PubMed Central

Murabito, Joanne M.; White, Charles C.; Kavousi, Maryam; Sun, Yan V.; Feitosa, Mary F.; Nambi, Vijay; Lamina, Claudia; Schillert, Arne; Coassin, Stefan; Bis, Joshua C.; Broer, Linda; Crawford, Dana C.; Franceschini, Nora; Frikke-Schmidt, Ruth; Haun, Margot; Holewijn, Suzanne; Huffman, Jennifer E.; Hwang, Shih-Jen; Kiechl, Stefan; Kollerits, Barbara; Montasser, May E.; Nolte, Ilja M.; Rudock, Megan E.; Senft, Andrea; Teumer, Alexander; van der Harst, Pim; Vitart, Veronique; Waite, Lindsay L.; Wood, Andrew R.; Wassel, Christina L.; Absher, Devin M.; Allison, Matthew A.; Amin, Najaf; Arnold, Alice; Asselbergs, Folkert W.; Aulchenko, Yurii; Bandinelli, Stefania; Barbalic, Maja; Boban, Mladen; Brown-Gentry, Kristin; Couper, David J.; Criqui, Michael H.; Dehghan, Abbas; Heijer, Martin den; Dieplinger, Benjamin; Ding, Jingzhong; Dörr, Marcus; Espinola-Klein, Christine; Felix, Stephan B.; Ferrucci, Luigi; Folsom, Aaron R.; Fraedrich, Gustav; Gibson, Quince; Goodloe, Robert; Gunjaca, Grgo; Haltmayer, Meinhard; Heiss, Gerardo; Hofman, Albert; Kieback, Arne; Kiemeney, Lambertus A.; Kolcic, Ivana; Kullo, Iftikhar J.; Kritchevsky, Stephen B.; Lackner, Karl J.; Li, Xiaohui; Lieb, Wolfgang; Lohman, Kurt; Meisinger, Christa; Melzer, David; Mohler, Emile R; Mudnic, Ivana; Mueller, Thomas; Navis, Gerjan; Oberhollenzer, Friedrich; Olin, Jeffrey W.; O’Connell, Jeff; O’Donnell, Christopher J.; Palmas, Walter; Penninx, Brenda W.; Petersmann, Astrid; Polasek, Ozren; Psaty, Bruce M.; Rantner, Barbara; Rice, Ken; Rivadeneira, Fernando; Rotter, Jerome I.; Seldenrijk, Adrie; Stadler, Marietta; Summerer, Monika; Tanaka, Toshiko; Tybjaerg-Hansen, Anne; Uitterlinden, Andre G.; van Gilst, Wiek H.; Vermeulen, Sita H.; Wild, Sarah H.; Wild, Philipp S.; Willeit, Johann; Zeller, Tanja; Zemunik, Tatijana; Zgaga, Lina; Assimes, Themistocles L.; Blankenberg, Stefan; Boerwinkle, Eric; Campbell, Harry; Cooke, John P.; de Graaf, Jacqueline; Herrington, David; Kardia, Sharon L. R.; Mitchell, Braxton D.; Murray, Anna; Münzel, Thomas; Newman, Anne; Oostra, Ben A.; Rudan, Igor; Shuldiner, Alan R.; Snieder, Harold; van Duijn, Cornelia M.; Völker, Uwe; Wright, Alan F.; Wichmann, H.-Erich; Wilson, James F.; Witteman, Jacqueline C.M.; Liu, Yongmei; Hayward, Caroline; Borecki, Ingrid B.; Ziegler, Andreas; North, Kari E.; Cupples, L. Adrienne; Kronenberg, Florian

2012-01-01

Background Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts. Methods and Results Continuous ABI and PAD (ABI≤0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ~2.5 million SNPs in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fixed-effects inverse variance weighted meta-analyses. There were a total of 41,692 participants of European ancestry (~60% women, mean ABI 1.02 to 1.19), including 3,409 participants with PAD and with GWAS data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (β= −0.006, p=2.46x10−8). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16,717). The association for rs10757269 strengthened in the combined discovery and replication analysis (p=2.65x10−9). No other SNP associations for ABI or PAD achieved genome-wide significance. However, two previously reported candidate genes for PAD and one SNP associated with coronary artery disease (CAD) were associated with ABI : DAB21P (rs13290547, p=3.6x10−5); CYBA (rs3794624, p=6.3x10−5); and rs1122608 (LDLR, p=0.0026). Conclusions GWAS in more than 40,000 individuals identified one genome-wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for CAD are associated with ABI. PMID:22199011

Wavelet analysis for wind fields estimation.

PubMed

Leite, Gladeston C; Ushizima, Daniela M; Medeiros, Fátima N S; de Lima, Gilson G

2010-01-01

Wind field analysis from synthetic aperture radar images allows the estimation of wind direction and speed based on image descriptors. In this paper, we propose a framework to automate wind direction retrieval based on wavelet decomposition associated with spectral processing. We extend existing undecimated wavelet transform approaches, by including à trous with B(3) spline scaling function, in addition to other wavelet bases as Gabor and Mexican-hat. The purpose is to extract more reliable directional information, when wind speed values range from 5 to 10 ms(-1). Using C-band empirical models, associated with the estimated directional information, we calculate local wind speed values and compare our results with QuikSCAT scatterometer data. The proposed approach has potential application in the evaluation of oil spills and wind farms.

Algorithm of reducing the false positives in IDS based on correlation Analysis

NASA Astrophysics Data System (ADS)

Liu, Jianyi; Li, Sida; Zhang, Ru

2018-03-01

This paper proposes an algorithm of reducing the false positives in IDS based on correlation Analysis. Firstly, the algorithm analyzes the distinguishing characteristics of false positives and real alarms, and preliminary screen the false positives; then use the method of attribute similarity clustering to the alarms and further reduces the amount of alarms; finally, according to the characteristics of multi-step attack, associated it by the causal relationship. The paper also proposed a reverse causation algorithm based on the attack association method proposed by the predecessors, turning alarm information into a complete attack path. Experiments show that the algorithm simplifies the number of alarms, improve the efficiency of alarm processing, and contribute to attack purposes identification and alarm accuracy improvement.

Residual-Mean Analysis of the Air-Sea Fluxes and Associated Oceanic Meridional Overturning

DTIC Science & Technology

2006-12-01

the adiabatic component of the MOC which is based entirely on the sea surface data . The coordinate system introduced in this study is somewhat...heat capacity of water. The technique utilizes the observational data based on meteorological re- analysis (density flux at the sea surface) and...Figure 8. Annual mean and temporal standard deviation of the zonally-averaged mixed- layer depth. The plotted data are based on Levitus 94 climatology

Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

PubMed Central

Wright, Fred A.; Strug, Lisa J.; Doshi, Vishal K.; Commander, Clayton W.; Blackman, Scott M.; Sun, Lei; Berthiaume, Yves; Cutler, David; Cojocaru, Andreea; Collaco, J. Michael; Corey, Mary; Dorfman, Ruslan; Goddard, Katrina; Green, Deanna; Kent, Jack W.; Lange, Ethan M.; Lee, Seunggeun; Li, Weili; Luo, Jingchun; Mayhew, Gregory M.; Naughton, Kathleen M.; Pace, Rhonda G.; Paré, Peter; Rommens, Johanna M.; Sandford, Andrew; Stonebraker, Jaclyn R.; Sun, Wei; Taylor, Chelsea; Vanscoy, Lori L.; Zou, Fei; Blangero, John; Zielenski, Julian; O’Neal, Wanda K.; Drumm, Mitchell L.; Durie, Peter R.; Knowles, Michael R.; Cutting, Garry R.

2012-01-01

A combined genome-wide association and linkage study was used to identify loci causing variation in CF lung disease severity. A significant association (P=3. 34 × 10-8) near EHF and APIP (chr11p13) was identified in F508del homozygotes (n=1,978). The association replicated in F508del homozygotes (P=0.006) from a separate family-based study (n=557), with P=1.49 × 10-9 for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family-based study identified a significant QTL on chromosome 20q13.2 (LOD=5.03). Our findings provide insight into the causes of variation in lung disease severity in CF and suggest new therapeutic targets for this life-limiting disorder. PMID:21602797

Using extreme phenotype sampling to identify the rare causal variants of quantitative traits in association studies.

PubMed

Li, Dalin; Lewinger, Juan Pablo; Gauderman, William J; Murcray, Cassandra Elizabeth; Conti, David

2011-12-01

Variants identified in recent genome-wide association studies based on the common-disease common-variant hypothesis are far from fully explaining the hereditability of complex traits. Rare variants may, in part, explain some of the missing hereditability. Here, we explored the advantage of the extreme phenotype sampling in rare-variant analysis and refined this design framework for future large-scale association studies on quantitative traits. We first proposed a power calculation approach for a likelihood-based analysis method. We then used this approach to demonstrate the potential advantages of extreme phenotype sampling for rare variants. Next, we discussed how this design can influence future sequencing-based association studies from a cost-efficiency (with the phenotyping cost included) perspective. Moreover, we discussed the potential of a two-stage design with the extreme sample as the first stage and the remaining nonextreme subjects as the second stage. We demonstrated that this two-stage design is a cost-efficient alternative to the one-stage cross-sectional design or traditional two-stage design. We then discussed the analysis strategies for this extreme two-stage design and proposed a corresponding design optimization procedure. To address many practical concerns, for example measurement error or phenotypic heterogeneity at the very extremes, we examined an approach in which individuals with very extreme phenotypes are discarded. We demonstrated that even with a substantial proportion of these extreme individuals discarded, an extreme-based sampling can still be more efficient. Finally, we expanded the current analysis and design framework to accommodate the CMC approach where multiple rare-variants in the same gene region are analyzed jointly. © 2011 Wiley Periodicals, Inc.

Using Extreme Phenotype Sampling to Identify the Rare Causal Variants of Quantitative Traits in Association Studies

PubMed Central

Li, Dalin; Lewinger, Juan Pablo; Gauderman, William J.; Murcray, Cassandra Elizabeth; Conti, David

2014-01-01

Variants identified in recent genome-wide association studies based on the common-disease common-variant hypothesis are far from fully explaining the hereditability of complex traits. Rare variants may, in part, explain some of the missing hereditability. Here, we explored the advantage of the extreme phenotype sampling in rare-variant analysis and refined this design framework for future large-scale association studies on quantitative traits. We first proposed a power calculation approach for a likelihood-based analysis method. We then used this approach to demonstrate the potential advantages of extreme phenotype sampling for rare variants. Next, we discussed how this design can influence future sequencing-based association studies from a cost-efficiency (with the phenotyping cost included) perspective. Moreover, we discussed the potential of a two-stage design with the extreme sample as the first stage and the remaining nonextreme subjects as the second stage. We demonstrated that this two-stage design is a cost-efficient alternative to the one-stage cross-sectional design or traditional two-stage design. We then discussed the analysis strategies for this extreme two-stage design and proposed a corresponding design optimization procedure. To address many practical concerns, for example measurement error or phenotypic heterogeneity at the very extremes, we examined an approach in which individuals with very extreme phenotypes are discarded. We demonstrated that even with a substantial proportion of these extreme individuals discarded, an extreme-based sampling can still be more efficient. Finally, we expanded the current analysis and design framework to accommodate the CMC approach where multiple rare-variants in the same gene region are analyzed jointly. PMID:21922541

[Association between patatin-like phospholipase domain-containing protein 3 gene rs738409 polymorphism and non-alcoholic fatty liver disease susceptibility: a meta-analysis].

PubMed

Wu, Pengbo; Shu, Yongxiang; Guo, Fang; Luo, Hesheng; Zhang, Guo; Tan, Shiyun

2015-01-01

To explore the association between patatin-like phospholipase domain-containing protein 3(PNPLA3) gene rs738409 polymorphism and the susceptibility of non-alcoholic fatty liver disease(NAFLD). Data bases were comprehensively searched to retrace all the related studies on the association between PNPLA3 gene rs738409 polymorphism and susceptibility. Of NAFLD, the pooled OR with 95% CI of the association between PNPLA3 gene rs738409 polymorphism and NAFLD susceptibility were performed using different genetic models. Subgroup analysis based on the source of population and sensitivity analysis was performed to detect the stability of results. 28 original studies with 6 216 patients and 8 218 controls were involved in the final combination of data. Findings from the meta-analyses showed that there were strong associations between PNPLA3 gene rs738409 polymorphism and the susceptibility of NAFLD, under different genetic model comparisons[GG vs. CC:OR = 2.42, 95%CI:1.83-3.21, P < 0.001;CG vs. CC:OR = 1.28, 95%CI:1.15-1.43, P < 0.001;CG+GG vs. CC:OR = 1.31, 95%CI:1.17-1.46, P < 0.001; GG vs. CC+GC:OR = 2.26, 95%CI:1.76-2.90, P < 0.001]. Similar results were found in both Asian and Caucasian populations. Results from the Meta-analysis strongly suggested that there appeared significant association between PNPLA3 gene rs738409 polymorphism and the susceptibility of NAFLD.

DIFFERENTIAL CROSS SECTION ANALYSIS IN KAON PHOTOPRODUCTION USING ASSOCIATED LEGENDRE POLYNOMIALS

DOE Office of Scientific and Technical Information (OSTI.GOV)

P. T. P. HUTAURUK, D. G. IRELAND, G. ROSNER

2009-04-01

Angular distributions of differential cross sections from the latest CLAS data sets,6 for the reaction γ + p→K+ + Λ have been analyzed using associated Legendre polynomials. This analysis is based upon theoretical calculations in Ref. 1 where all sixteen observables in kaon photoproduction can be classified into four Legendre classes. Each observable can be described by an expansion of associated Legendre polynomial functions. One of the questions to be addressed is how many associated Legendre polynomials are required to describe the data. In this preliminary analysis, we used data models with different numbers of associated Legendre polynomials. We thenmore » compared these models by calculating posterior probabilities of the models. We found that the CLAS data set needs no more than four associated Legendre polynomials to describe the differential cross section data. In addition, we also show the extracted coefficients of the best model.« less

The Associations between RNA Splicing Complex Gene SF3A1 Polymorphisms and Colorectal Cancer Risk in a Chinese Population.

PubMed

Chen, Xiaohua; Du, Hua; Liu, Binjian; Zou, Li; Chen, Wei; Yang, Yang; Zhu, Ying; Gong, Yajie; Tian, Jianbo; Li, Feng; Zhong, Shan

2015-01-01

Aberrant alternative splicing included alterations in components of the mRNA splicing machinery often occurred in colon cancer. However, the role of SF3A1, one key component of the mRNA splicing machinery, on colorectal cancer (CRC) risk was still not elucidated. We performed a hospital-based case-control study containing 801 CRC patients and 817 cancer-free controls to examine the association between SF3A1 polymorphisms and CRC risk in a Chinese population. Four candidate SNPs (rs10376, rs5753073, rs2839998 and rs2074733) were selected based on bioinformatics analysis and previous findings. The results showed no significant associations between these SNPs and CRC risk (P > 0.05). Besides, the stratified analysis based on the smoking and alcohol use status obtained no statistically significant results. Our study was the first one to investigate the association between SF3A1 polymorphisms and CRC risk. The results suggested these four SNPs in SF3A1 were not associated with CRC risk in a Chinese population, however, further more studies are needed to confirm our findings.

Work-family conflicts and self-reported work ability: cross-sectional findings in women with chronic musculoskeletal disorders.

PubMed

Bethge, Matthias; Borngräber, Yvonne

2015-03-18

Under conditions of gender-specific division of paid employment and unpaid childcare and housework, rising employment of women increases the likelihood that they will be faced with work-family conflicts. As recent research indicates, such conflicts might also contribute to musculoskeletal disorders. However, research in patient samples is needed to clarify how important these conflicts are for relevant health-related measures of functioning (e.g., work ability). We therefore examined, in a sample of women with chronic musculoskeletal disorders, the indirect and direct associations between the indicators of work-family conflicts and self-reported work ability as well as whether the direct effects remained significant after adjustment for covariates. A cross-sectional questionnaire-based study was conducted. Participants were recruited from five rehabilitation centers. Work-family conflicts were assessed by four scales referring to time- and strain-based work interference with family (WIF) and family interference with work (FIW). Self-reported work ability was measured by the Work Ability Index. A confirmatory factor analysis was performed to approve the anticipated four-factor structure of the work-family conflict measure. Direct and indirect associations between work-family conflict indicators and self-reported work ability were examined by path model analysis. Multivariate regression models were performed to calculate adjusted estimators of the direct effects of strain-based WIF and FIW on work ability. The study included 351 employed women. The confirmatory factor analysis provided support for the anticipated four-factor structure of the work-family conflict measure. The path model analysis identified direct effects of both strain-based scales on self-reported work ability. The time-based scales were indirectly associated with work ability via the strain-based scales. Adjusted regression analyses showed that a five-point increase in strain-based WIF or FIW was associated with a four- and two-point decrease in self-reported work ability, respectively. The standardized regression coefficients were β = 0.35 and β = 0.12. Our findings indicate that work-family conflicts are associated with poor work ability in female patients with chronic musculoskeletal disorders. However, longitudinal research is needed to establish a causal relationship. Better compatibility of work and family life might be an environmental facilitator of better rehabilitation outcomes in female patients with musculoskeletal disorders.

Meta-Analysis of the Association between Tea Intake and the Risk of Cognitive Disorders

PubMed Central

Ma, Qing-Ping; Huang, Chen; Cui, Qiao-Yun; Yang, Ding-Jun; Sun, Kang; Chen, Xuan; Li, Xing-Hui

2016-01-01

Background Alzheimer’s disease is a common neurodegenerative disorder in elderly. This study was aimed to systematically evaluate the association between tea intake and the risk of cognitive disorders by meta-analysis. Methods and Findings PubMed, Embase and Wanfang databases were systematically searched and a total of 26 observational studies were included in this study. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated and pooled by using fixed or random effects models according to the degree of heterogeneity. Results The overall pooled analysis indicated that tea intake could significantly reduce the risk of cognitive disorders (OR = 0.65, 95%CI = 0.58–0.73). Subgroup analyses were conducted based on study design, population, frequency of tea drinking and type of cognitive disorders. The results showed that tea drinking was significantly associated with the reduced incidence of cognitive disorders in all of subgroups based on study design and frequency of tea drinking. In particular, tea drinking was inversely associated with the risk of cognitive impairment (CoI), mild cognitive impairment (MCI), cognitive decline and ungrouped cognitive disorders. Moreover, for population subgroups, the significant association was only found in Chinese people. Conclusion Our study suggests that daily tea drinking is associated with decreased risk of CoI, MCI and cognitive decline in the elderly. However, the association between tea intake and Alzheimer’s disease remains elusive. PMID:27824892

A fast boosting-based screening method for large-scale association study in complex traits with genetic heterogeneity.

PubMed

Wang, Lu-Yong; Fasulo, D

2006-01-01

Genome-wide association study for complex diseases will generate massive amount of single nucleotide polymorphisms (SNPs) data. Univariate statistical test (i.e. Fisher exact test) was used to single out non-associated SNPs. However, the disease-susceptible SNPs may have little marginal effects in population and are unlikely to retain after the univariate tests. Also, model-based methods are impractical for large-scale dataset. Moreover, genetic heterogeneity makes the traditional methods harder to identify the genetic causes of diseases. A more recent random forest method provides a more robust method for screening the SNPs in thousands scale. However, for more large-scale data, i.e., Affymetrix Human Mapping 100K GeneChip data, a faster screening method is required to screening SNPs in whole-genome large scale association analysis with genetic heterogeneity. We propose a boosting-based method for rapid screening in large-scale analysis of complex traits in the presence of genetic heterogeneity. It provides a relatively fast and fairly good tool for screening and limiting the candidate SNPs for further more complex computational modeling task.

A linkage and family-based association analysis of a potential neurocognitive endophenotype of bipolar disorder.

PubMed

Savitz, Jonathan; van der Merwe, Lize; Solms, Mark; Ramesar, Rajkumar

2007-01-01

The identification of the genetic variants underpinning bipolar disorder (BPD) has been impeded by a complex pattern of inheritance characterized by genetic and phenotypic heterogeneity, genetic epistasis, and gene-environment interactions. In this paper two strategies were used to ameliorate these confounding factors. A unique South African sample including 190 individuals of the relatively, reproductively isolated Afrikaner population was assessed with a battery of neuropsychological tests in an attempt to identify a BPD-associated quantitative trait or endophenotype. BPD individuals performed significantly worse than their unaffected relatives on visual and verbal memory tasks, a finding congruent with the literature. Afocused linkage and family-based association study was carried out using this memory-related endophenotype. In the largest 77-strong Afrikaner pedigree significant evidence for linkage was detected on chromosome 22q11, a region previously implicated in BPD. The quantitative transmission disequilibrium tests-based association analysis suggested that functional variants of the DRD4 and MAO-A genes modulate memory-related cognition. We speculate that polymorphisms at these loci may predispose to a subtype of BPD characterized by memory-related deficits.

Sports Stars: Analyzing the Performance of Astronomers at Visualization-based Discovery

NASA Astrophysics Data System (ADS)

Fluke, C. J.; Parrington, L.; Hegarty, S.; MacMahon, C.; Morgan, S.; Hassan, A. H.; Kilborn, V. A.

2017-05-01

In this data-rich era of astronomy, there is a growing reliance on automated techniques to discover new knowledge. The role of the astronomer may change from being a discoverer to being a confirmer. But what do astronomers actually look at when they distinguish between “sources” and “noise?” What are the differences between novice and expert astronomers when it comes to visual-based discovery? Can we identify elite talent or coach astronomers to maximize their potential for discovery? By looking to the field of sports performance analysis, we consider an established, domain-wide approach, where the expertise of the viewer (i.e., a member of the coaching team) plays a crucial role in identifying and determining the subtle features of gameplay that provide a winning advantage. As an initial case study, we investigate whether the SportsCode performance analysis software can be used to understand and document how an experienced Hi astronomer makes discoveries in spectral data cubes. We find that the process of timeline-based coding can be applied to spectral cube data by mapping spectral channels to frames within a movie. SportsCode provides a range of easy to use methods for annotation, including feature-based codes and labels, text annotations associated with codes, and image-based drawing. The outputs, including instance movies that are uniquely associated with coded events, provide the basis for a training program or team-based analysis that could be used in unison with discipline specific analysis software. In this coordinated approach to visualization and analysis, SportsCode can act as a visual notebook, recording the insight and decisions in partnership with established analysis methods. Alternatively, in situ annotation and coding of features would be a valuable addition to existing and future visualization and analysis packages.

Where Are the Global Rankings Leading Us? An Analysis of Recent Methodological Changes and New Developments

ERIC Educational Resources Information Center

Rauhvargers, Andrejs

2014-01-01

This article is based on the analysis of the changes in global university rankings and the new "products" based on rankings data in the period since mid-2011. It is a summary and continuation of the European University Association (EUA)-commissioned report "Global University Rankings Their Impact, Report II" which was launched…

Meta-analysis: Association between hypoglycaemia and serious adverse events in older patients.

PubMed

Mattishent, Katharina; Loke, Yoon Kong

2016-07-01

We aimed to conduct a meta-analysis of serious adverse events (macro- and microvascular events, falls and fractures, death) associated with hypoglycaemia in older patients. We searched MEDLINE and EMBASE spanning a ten-year period up to March 2015 (with automated PubMed updates to October 2015). We selected observational studies reporting on hypoglycaemia and associated serious adverse events, and conducted a meta-analysis. We assessed study validity based on ascertainment of hypoglycaemia, adverse events and adjustment for confounders. We included 17 studies involving 1.86 million participants. Meta-analysis of eight studies demonstrated that hypoglycemic episodes were associated with macrovascular complications, odds ratio (OR) 1.83 (95% confidence interval [CI] 1.64, 2.05), and microvascular complications in two studies OR 1.77 (95% CI 1.49, 2.10). Meta-analysis of four studies demonstrated an association between hypoglycaemia and falls or fractures, OR 1.89 (95% CI 1.54, 2.32) and 1.92 (95% CI 1.56, 2.38) respectively. Hypoglycaemia was associated with increased likelihood of death in a meta-analysis of eight studies, OR 2.04 (95% Confidence Interval 1.68, 2.47). Our meta-analysis raises major concerns about a range of serious adverse events associated with hypoglycaemia. Clinicians should prioritize individualized therapy and closer monitoring strategies to avoid hypoglycaemia in susceptible older patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

PubMed Central

Davies, G; Armstrong, N; Bis, J C; Bressler, J; Chouraki, V; Giddaluru, S; Hofer, E; Ibrahim-Verbaas, C A; Kirin, M; Lahti, J; van der Lee, S J; Le Hellard, S; Liu, T; Marioni, R E; Oldmeadow, C; Postmus, I; Smith, A V; Smith, J A; Thalamuthu, A; Thomson, R; Vitart, V; Wang, J; Yu, L; Zgaga, L; Zhao, W; Boxall, R; Harris, S E; Hill, W D; Liewald, D C; Luciano, M; Adams, H; Ames, D; Amin, N; Amouyel, P; Assareh, A A; Au, R; Becker, J T; Beiser, A; Berr, C; Bertram, L; Boerwinkle, E; Buckley, B M; Campbell, H; Corley, J; De Jager, P L; Dufouil, C; Eriksson, J G; Espeseth, T; Faul, J D; Ford, I; Scotland, Generation; Gottesman, R F; Griswold, M E; Gudnason, V; Harris, T B; Heiss, G; Hofman, A; Holliday, E G; Huffman, J; Kardia, S L R; Kochan, N; Knopman, D S; Kwok, J B; Lambert, J-C; Lee, T; Li, G; Li, S-C; Loitfelder, M; Lopez, O L; Lundervold, A J; Lundqvist, A; Mather, K A; Mirza, S S; Nyberg, L; Oostra, B A; Palotie, A; Papenberg, G; Pattie, A; Petrovic, K; Polasek, O; Psaty, B M; Redmond, P; Reppermund, S; Rotter, J I; Schmidt, H; Schuur, M; Schofield, P W; Scott, R J; Steen, V M; Stott, D J; van Swieten, J C; Taylor, K D; Trollor, J; Trompet, S; Uitterlinden, A G; Weinstein, G; Widen, E; Windham, B G; Jukema, J W; Wright, A F; Wright, M J; Yang, Q; Amieva, H; Attia, J R; Bennett, D A; Brodaty, H; de Craen, A J M; Hayward, C; Ikram, M A; Lindenberger, U; Nilsson, L-G; Porteous, D J; Räikkönen, K; Reinvang, I; Rudan, I; Sachdev, P S; Schmidt, R; Schofield, P R; Srikanth, V; Starr, J M; Turner, S T; Weir, D R; Wilson, J F; van Duijn, C; Launer, L; Fitzpatrick, A L; Seshadri, S; Mosley, T H; Deary, I J

2015-01-01

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10−9, MIR2113; rs17522122, P=2.55 × 10−8, AKAP6; rs10119, P=5.67 × 10−9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10−6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10−17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C. PMID:25644384

[The method and application to construct experience recommendation platform of acupuncture ancient books based on data mining technology].

PubMed

Chen, Chuyun; Hong, Jiaming; Zhou, Weilin; Lin, Guohua; Wang, Zhengfei; Zhang, Qufei; Lu, Cuina; Lu, Lihong

2017-07-12

To construct a knowledge platform of acupuncture ancient books based on data mining technology, and to provide retrieval service for users. The Oracle 10 g database was applied and JAVA was selected as development language; based on the standard library and ancient books database established by manual entry, a variety of data mining technologies, including word segmentation, speech tagging, dependency analysis, rule extraction, similarity calculation, ambiguity analysis, supervised classification technology were applied to achieve text automatic extraction of ancient books; in the last, through association mining and decision analysis, the comprehensive and intelligent analysis of disease and symptom, meridians, acupoints, rules of acupuncture and moxibustion in acupuncture ancient books were realized, and retrieval service was provided for users through structure of browser/server (B/S). The platform realized full-text retrieval, word frequency analysis and association analysis; when diseases or acupoints were searched, the frequencies of meridian, acupoints (diseases) and techniques were presented from high to low, meanwhile the support degree and confidence coefficient between disease and acupoints (special acupoint), acupoints and acupoints in prescription, disease or acupoints and technique were presented. The experience platform of acupuncture ancient books based on data mining technology could be used as a reference for selection of disease, meridian and acupoint in clinical treatment and education of acupuncture and moxibustion.

Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: protocol for a collaborative meta-analysis

PubMed Central

Hartwig, Fernando Pires; Davies, Neil Martin; Horta, Bernardo Lessa; Victora, Cesar Gomes; Davey Smith, George

2016-01-01

Introduction Evidence from observational studies and randomised controlled trials suggests that breastfeeding is positively associated with IQ, possibly because breast milk is a source of long-chain polyunsaturated fatty acids. Different studies have detected gene-breastfeeding interactions involving FADS2 variants and intelligence. However, findings are inconsistent regarding the direction of such effect modification. Methods/design To clarify how FADS2 and breastfeeding interact in their association with IQ, we are conducting a consortium-based meta-analysis of independent studies. Results produced by each individual study using standardised analysis scripts and harmonised data will be used. Inclusion criteria: breastfeeding, IQ and either rs174575 or rs1535 polymorphisms available; and being of European ancestry. Exclusion criteria: twin studies; only poorly imputed genetic data available; or unavailability of proper ethics approval. Studies will be invited based on being known to have at least some of the required data, or suggested by participating studies as potentially eligible. This inclusive approach will favour achieving a larger sample size and be less prone to publication bias. Discussion Improving current understanding of FADS2-breastfeeding interaction may provide important biological insights regarding the importance of long-chain polyunsaturated fatty acids for the breastfeeding-IQ association. This meta-analysis will help to improve such knowledge by replicating earlier studies, conducting additional analysis and evaluating different sources of heterogeneity. Publishing this protocol will minimise the possibility of bias due to post hoc changes to the analysis protocol. PMID:27311901

Association genetics and transcriptome analysis reveal a gibberellin-responsive pathway involved in regulating photosynthesis.

PubMed

Xie, Jianbo; Tian, Jiaxing; Du, Qingzhang; Chen, Jinhui; Li, Ying; Yang, Xiaohui; Li, Bailian; Zhang, Deqiang

2016-05-01

Gibberellins (GAs) regulate a wide range of important processes in plant growth and development, including photosynthesis. However, the mechanism by which GAs regulate photosynthesis remains to be understood. Here, we used multi-gene association to investigate the effect of genes in the GA-responsive pathway, as constructed by RNA sequencing, on photosynthesis, growth, and wood property traits, in a population of 435 Populus tomentosa By analyzing changes in the transcriptome following GA treatment, we identified many key photosynthetic genes, in agreement with the observed increase in measurements of photosynthesis. Regulatory motif enrichment analysis revealed that 37 differentially expressed genes related to photosynthesis shared two essential GA-related cis-regulatory elements, the GA response element and the pyrimidine box. Thus, we constructed a GA-responsive pathway consisting of 47 genes involved in regulating photosynthesis, including GID1, RGA, GID2, MYBGa, and 37 photosynthetic differentially expressed genes. Single nucleotide polymorphism (SNP)-based association analysis showed that 142 SNPs, representing 40 candidate genes in this pathway, were significantly associated with photosynthesis, growth, and wood property traits. Epistasis analysis uncovered interactions between 310 SNP-SNP pairs from 37 genes in this pathway, revealing possible genetic interactions. Moreover, a structural gene-gene matrix based on a time-course of transcript abundances provided a better understanding of the multi-gene pathway affecting photosynthesis. The results imply a functional role for these genes in mediating photosynthesis, growth, and wood properties, demonstrating the potential of combining transcriptome-based regulatory pathway construction and genetic association approaches to detect the complex genetic networks underlying quantitative traits. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Clinical Implications of Cluster Analysis-Based Classification of Acute Decompensated Heart Failure and Correlation with Bedside Hemodynamic Profiles.

PubMed

Ahmad, Tariq; Desai, Nihar; Wilson, Francis; Schulte, Phillip; Dunning, Allison; Jacoby, Daniel; Allen, Larry; Fiuzat, Mona; Rogers, Joseph; Felker, G Michael; O'Connor, Christopher; Patel, Chetan B

2016-01-01

Classification of acute decompensated heart failure (ADHF) is based on subjective criteria that crudely capture disease heterogeneity. Improved phenotyping of the syndrome may help improve therapeutic strategies. To derive cluster analysis-based groupings for patients hospitalized with ADHF, and compare their prognostic performance to hemodynamic classifications derived at the bedside. We performed a cluster analysis on baseline clinical variables and PAC measurements of 172 ADHF patients from the ESCAPE trial. Employing regression techniques, we examined associations between clusters and clinically determined hemodynamic profiles (warm/cold/wet/dry). We assessed association with clinical outcomes using Cox proportional hazards models. Likelihood ratio tests were used to compare the prognostic value of cluster data to that of hemodynamic data. We identified four advanced HF clusters: 1) male Caucasians with ischemic cardiomyopathy, multiple comorbidities, lowest B-type natriuretic peptide (BNP) levels; 2) females with non-ischemic cardiomyopathy, few comorbidities, most favorable hemodynamics; 3) young African American males with non-ischemic cardiomyopathy, most adverse hemodynamics, advanced disease; and 4) older Caucasians with ischemic cardiomyopathy, concomitant renal insufficiency, highest BNP levels. There was no association between clusters and bedside-derived hemodynamic profiles (p = 0.70). For all adverse clinical outcomes, Cluster 4 had the highest risk, and Cluster 2, the lowest. Compared to Cluster 4, Clusters 1-3 had 45-70% lower risk of all-cause mortality. Clusters were significantly associated with clinical outcomes, whereas hemodynamic profiles were not. By clustering patients with similar objective variables, we identified four clinically relevant phenotypes of ADHF patients, with no discernable relationship to hemodynamic profiles, but distinct associations with adverse outcomes. Our analysis suggests that ADHF classification using simultaneous considerations of etiology, comorbid conditions, and biomarker levels, may be superior to bedside classifications.

Haplotype-Based Association Analysis via Variance-Components Score Test

PubMed Central

Tzeng, Jung-Ying ; Zhang, Daowen 

2007-01-01

Haplotypes provide a more informative format of polymorphisms for genetic association analysis than do individual single-nucleotide polymorphisms. However, the practical efficacy of haplotype-based association analysis is challenged by a trade-off between the benefits of modeling abundant variation and the cost of the extra degrees of freedom. To reduce the degrees of freedom, several strategies have been considered in the literature. They include (1) clustering evolutionarily close haplotypes, (2) modeling the level of haplotype sharing, and (3) smoothing haplotype effects by introducing a correlation structure for haplotype effects and studying the variance components (VC) for association. Although the first two strategies enjoy a fair extent of power gain, empirical evidence showed that VC methods may exhibit only similar or less power than the standard haplotype regression method, even in cases of many haplotypes. In this study, we report possible reasons that cause the underpowered phenomenon and show how the power of the VC strategy can be improved. We construct a score test based on the restricted maximum likelihood or the marginal likelihood function of the VC and identify its nontypical limiting distribution. Through simulation, we demonstrate the validity of the test and investigate the power performance of the VC approach and that of the standard haplotype regression approach. With suitable choices for the correlation structure, the proposed method can be directly applied to unphased genotypic data. Our method is applicable to a wide-ranging class of models and is computationally efficient and easy to implement. The broad coverage and the fast and easy implementation of this method make the VC strategy an effective tool for haplotype analysis, even in modern genomewide association studies. PMID:17924336

Association between metabolic syndrome and bone fracture risk: A community-based study using a fracture risk assessment tool.

PubMed

Yu, Chia-Ying; Chen, Fang-Ping; Chen, Li-Wei; Kuo, Sheng-Fong; Chien, Rong-Nan

2017-12-01

Osteoporosis and metabolic syndrome (MS) share similar risk factors. Previous studies of association between bone marrow density (BMD) and MS are controversial. Moreover, some studies revealed that MS is associated with BMD but not with bone fracture. In clinical practice, patients pay more attention to bone fracture risk than BMD values. Hence, this study aimed to evaluate the association between MS and the 10-year bone fracture risk probability using a fracture risk assessment tool (FRAX) from community-based data. From March 2014 to August 2015, 2689 participants (897 men and 1792 women) were enrolled in this study. Inflammatory cytokines, such as tumor necrosis factor alpha and C-reactive protein, and adipokines were included for analysis.The mean age was 60.2 ± 10.7 years in men and 58.9 ± 9.6 years in women. The percentage of MS was 27.6% in men and 27.9% in women. Participants were divided into 2 groups, those with or without MS. Compared with women without MS, women with MS had a higher rate of fracture risk (22.8% vs 16.3%, P = .001). In contrast, men with MS had a lower rate of fracture risk then men without MS (5.6% vs 12.3%, P = .004). However, MS loss the association with a high bone fracture risk in men based on multivariate logistical regression analysis, after adjusting for confounding factor of body mass index (BMI). Conclusively, the result of regression analysis between MS and the bone fracture risk may be different in men and women, and BMI was an important confounding factor to interfere with the regression analysis. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Reduced flexibility associated with metabolic syndrome in community-dwelling elders.

PubMed

Chang, Ke-Vin; Hung, Chen-Yu; Li, Chia-Ming; Lin, Yu-Hung; Wang, Tyng-Guey; Tsai, Keh-Sung; Han, Der-Sheng

2015-01-01

The ageing process may lead to reductions in physical fitness, a known risk factor in the development of metabolic syndrome. The purpose of the current study was to evaluate cross-sectional and combined associations of metabolic syndrome with body composition and physical fitness in a community based geriatric population. A total of 628 community-dwelling elders attending a geriatric health examination were enrolled in the study. The diagnosis of metabolic syndrome was based on the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criterion with Asian cutoff of waist girth was adopted in this study. Body composition was obtained using bioimpedance analysis, and physical fitness was evaluated through the measurement of muscle strength (handgrip force), lower extremity muscle endurance (sit-to-stand test), flexibility (sit-and-reach test), and cardiorespiratory endurance (2-minute step test). Multivariable logistic regression and correlation analysis were performed to determine the association of metabolic syndrome with body composition and functionality variables. Metabolic syndrome was associated with increased skeletal muscle index (SMI) (odds ratio (OR), 1.61, 95% confidence interval (CI), 1.25-2.07) and decreased flexibility (OR, 0.97, 95% CI, 0.95-0.99) compared with those without metabolic syndrome. When body mass index was accounted for in the analysis, the association of SMI with metabolic syndrome was reduced. Waist circumference was positively correlated with SMI but negatively correlated with flexibility, whereas high density lipoprotein was positively correlated with flexibility but negatively correlated with SMI. Reduced flexibility was positively associated with metabolic syndrome independent of age, gender, body composition, and functionality measurements in a community based geriatric population. Significant associations between metabolic syndrome with muscle strength and cardiorespiratory fitness in the elderly were not observed. Furthermore, flexibility should be included in the complete evaluation for metabolic syndrome.

Rare variant association analysis in case-parents studies by allowing for missing parental genotypes.

PubMed

Li, Yumei; Xiang, Yang; Xu, Chao; Shen, Hui; Deng, Hongwen

2018-01-15

The development of next-generation sequencing technologies has facilitated the identification of rare variants. Family-based design is commonly used to effectively control for population admixture and substructure, which is more prominent for rare variants. Case-parents studies, as typical strategies in family-based design, are widely used in rare variant-disease association analysis. Current methods in case-parents studies are based on complete case-parents data; however, parental genotypes may be missing in case-parents trios, and removing these data may lead to a loss in statistical power. The present study focuses on testing for rare variant-disease association in case-parents study by allowing for missing parental genotypes. In this report, we extended the collapsing method for rare variant association analysis in case-parents studies to allow for missing parental genotypes, and investigated the performance of two methods by using the difference of genotypes between affected offspring and their corresponding "complements" in case-parent trios and TDT framework. Using simulations, we showed that, compared with the methods just only using complete case-parents data, the proposed strategy allowing for missing parental genotypes, or even adding unrelated affected individuals, can greatly improve the statistical power and meanwhile is not affected by population stratification. We conclude that adding case-parents data with missing parental genotypes to complete case-parents data set can greatly improve the power of our strategy for rare variant-disease association.

A genome-wide association study of corneal astigmatism: The CREAM Consortium

PubMed Central

Shah, Rupal L.; Li, Qing; Zhao, Wanting; Tedja, Milly S.; Tideman, J. Willem L.; Khawaja, Anthony P.; Fan, Qiao; Yazar, Seyhan; Williams, Katie M.; Verhoeven, Virginie J.M.; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J.; Pärssinen, Olavi; Wedenoja, Juho; Biino, Ginevra; Concas, Maria Pina; Uitterlinden, André; Rivadeneira, Fernando; Jaddoe, Vincent W.V.; Hysi, Pirro G.; Sim, Xueling; Tan, Nicholas; Tham, Yih-Chung; Sensaki, Sonoko; Hofman, Albert; Vingerling, Johannes R.; Jonas, Jost B.; Mitchell, Paul; Hammond, Christopher J.; Höhn, René; Baird, Paul N.; Wong, Tien-Yin; Cheng, Chinfsg-Yu; Teo, Yik Ying; Mackey, David A.; Williams, Cathy; Saw, Seang-Mei; Klaver, Caroline C.W.; Bailey-Wilson, Joan E.

2018-01-01

Purpose To identify genes and genetic markers associated with corneal astigmatism. Methods A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. Results The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08–1.16), p=5.55×10−9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans—claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). Conclusions In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism. PMID:29422769

Some reflections on 25 years of the association for behavior analysis: Past, present, and future

PubMed Central

Morris, Edward K.; Baer, Donald M.; Favell, Judith E.; Glenn, Sigrid S.; Hineline, Philip N.; Malott, Maria E.; Michael, Jack

2001-01-01

This paper offers some reflections on the discipline and profession of behavior analysis, as well as on the Association for Behavior Analysis (ABA), on the occasion of the association's 25th anniversary. It is based on a panel session conducted at the 1999 convention that included six past presidents of ABA (Donald M. Baer, Judith E. Favell, Sigrid S. Glenn, Philip N. Hineline, Jack Michael, and Edward K. Morris) and its current Executive Director and Secretary-Treasurer (Maria E. Malott). Among the topics addressed were (a) the survival of behavior analysis in university and cultural contexts, (b) the training of behavior-analytic researchers and practitioners, (c) relations between basic and applied research, (d) convergences between behavior analysis and other disciplines, (e) the structure and function of ABA, and (f) the importance of students for the future of the association, the discipline, and the profession. Questions from the audience raised issues concerning the relevance of major behavior-analytic journals, advances in behavior analysis since the death of B. F. Skinner, and the availability of accessible, popular material on applied behavior analysis. PMID:22478359

An Analysis of the Bases Used By Library Evaluators in the Accrediting Process of the Southern Association of Colleges and Schools.

ERIC Educational Resources Information Center

Yates, Dudley V.

Seventy-seven of ninety library evaluators of the Southern Association of Colleges and Schools (SACS) responded to a 1973 questionnaire to determine: (1) if evaluative criteria used are based with an authority other than SACS; and (2) if certain methods, procedures, and techniques employed by evaluators could be used to construct an ideal…

Design Criteria for Adaptive Roadway Lighting

DOT National Transportation Integrated Search

2014-07-01

This report provides the background and analysis used to develop criteria for the implementation of an adaptive lighting system for roadway lighting. Based on the analysis of crashes and lighting performance, a series of criteria and the associated d...

Association between Parental Emotional Symptoms and Child Antisocial Behaviour: What Is Specific and Is It Mediated by Parenting?

ERIC Educational Resources Information Center

Hautmann, Christopher; Eichelberger, Ilka; Hanisch, Charlotte; Plück, Julia; Walter, Daniel; Döpfner, Manfred

2015-01-01

Parental anxiety and depression are associated with antisocial behaviour of children. Several mechanisms may mediate this association. The aim of this study was to test whether parenting is a mediator of the association of parental anxiety and depression with the antisocial social behaviour of preschool children. The analysis was based on…

National Practice Patterns for Clinical T1N0 Nasopharyngeal Cancer in the Elderly: A National Cancer Data Base Analysis.

PubMed

Post, Carl M; Lin, Chi; Adeberg, Sebastian; Gupta, Mrigank; Zhen, Weining; Verma, Vivek

2018-03-01

The standard of care for T1N0 nasopharyngeal cancer (NPC) is definitive radiation therapy (RT). However, practice patterns in the elderly may not necessarily follow national guidelines. Herein, we investigated national practice patterns for T1N0 NPC. The National Cancer Data Base (NCDB) was queried for clinical T1N0 primary NPC cases (2004-2013) in patients ≥70 years old. Patient, tumor, and treatment parameters were extracted. Kaplan-Meier analysis was used to compare overall survival (OS) between patients receiving RT versus those under observation. Logistic regression was used to examine variables associated with receipt of RT. Cox proportional hazards modeling determined variables associated with OS. Landmark analysis of patients surviving 1 year or more was performed to assess survival differences between groups. In total, data of 147 patients were analyzed. RT was delivered to 89 patients (61%), whereas 58 (39%) patients underwent observation. On multivariable analysis, older patients were less likely to receive RT (p=0.003), but there were no differences between groups in terms of Charlson-Deyo comorbidity index. Median and 5-year OS in patients receiving RT versus those under observation were 71 and 33 months, and 59% and 48% (p=0.011), respectively. For patients surviving 1 year or more (n=96), there was a strong trend showing that receipt of RT was associated with better median and 5-year OS. This National Data Base analysis shows that observation is relatively common for T1N0 NPC in the elderly, but is associated with poorer survival. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms.

PubMed

Esplin, M Sean; Manuck, Tracy A; Varner, Michael W; Christensen, Bryce; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Huang, Hao; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M; Ilekis, John

2015-09-01

We sought to use an innovative tool that is based on common biologic pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB) to enhance investigators' ability to identify and to highlight common mechanisms and underlying genetic factors that are responsible for SPTB. We performed a secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks' gestation. Each woman was assessed for the presence of underlying SPTB causes. A hierarchic cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis with the use of VEGAS software. One thousand twenty-eight women with SPTB were assigned phenotypes. Hierarchic clustering of the phenotypes revealed 5 major clusters. Cluster 1 (n = 445) was characterized by maternal stress; cluster 2 (n = 294) was characterized by premature membrane rupture; cluster 3 (n = 120) was characterized by familial factors, and cluster 4 (n = 63) was characterized by maternal comorbidities. Cluster 5 (n = 106) was multifactorial and characterized by infection (INF), decidual hemorrhage (DH), and placental dysfunction (PD). These 3 phenotypes were correlated highly by χ(2) analysis (PD and DH, P < 2.2e-6; PD and INF, P = 6.2e-10; INF and DH, (P = .0036). Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. We identified 5 major clusters of SPTB based on a phenotype tool and hierarch clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors that were underlying SPTB. Copyright © 2015 Elsevier Inc. All rights reserved.

Time Spent Walking and Risk of Diabetes in Japanese Adults: The Japan Public Health Center-Based Prospective Diabetes Study

PubMed Central

Kabeya, Yusuke; Goto, Atsushi; Kato, Masayuki; Matsushita, Yumi; Takahashi, Yoshihiko; Isogawa, Akihiro; Inoue, Manami; Mizoue, Tetsuya; Tsugane, Shoichiro; Kadowaki, Takashi; Noda, Mitsuhiko

2016-01-01

Background The association between time spent walking and risk of diabetes was investigated in a Japanese population-based cohort. Methods Data from the Japan Public Health Center-based Prospective Diabetes cohort were analyzed. The surveys of diabetes were performed at baseline and at the 5-year follow-up. Time spent walking per day was assessed using a self-reported questionnaire (<30 minutes, 30 minutes to <1 hour, 1 to <2 hours, or ≥2 hours). A cross-sectional analysis was performed among 26 488 adults in the baseline survey. Logistic regression was used to examine the association between time spent walking and the presence of unrecognized diabetes. We then performed a longitudinal analysis that was restricted to 11 101 non-diabetic adults who participated in both the baseline and 5-year surveys. The association between time spent walking and the incidence of diabetes during the 5 years was examined. Results In the cross-sectional analysis, 1058 participants had unrecognized diabetes. Those with time spent walking of <30 minutes per day had increased odds of having diabetes in relation to those with time spent walking of ≥2 hours (adjusted odds ratio [OR] 1.23; 95% CI, 1.02–1.48). In the longitudinal analysis, 612 participants developed diabetes during the 5 years of follow-up. However, a significant association between time spent walking and the incidence of diabetes was not observed. Conclusions Increased risk of diabetes was implied in those with time spent walking of <30 minutes per day, although the longitudinal analysis failed to show a significant result. PMID:26725285

Reexamination of Total Fluid Intake and Bladder Cancer in the Health Professionals Follow-Up Study Cohort

PubMed Central

Zhou, Jiachen; Smith, Scott; Giovannucci, Edward; Michaud, Dominique S.

2012-01-01

It has been hypothesized that high fluid intake may reduce contact time between carcinogens and bladder epithelium and consequently reduce carcinogenesis. Epidemiologic studies examining fluid intake and bladder cancer have been extremely inconsistent, ranging from strong inverse to strong positive associations. The authors reevaluated the association between fluid intake and bladder cancer among 47,909 participants in the prospective Health Professionals Follow-up Study over a period of 22 years. During follow-up (1986–2008), 823 incident bladder cancer cases were diagnosed. Information on fluid intake was collected by using the food frequency questionnaire at baseline and every 4 years thereafter. Cox proportional hazard regression analysis was used to adjust for risk factors for bladder cancer. Total fluid intake was inversely associated with bladder cancer when the analysis was based on the baseline diet (relative risk = 0.76, 95% confidence interval: 0.60, 0.97), comparing the highest total daily fluid intake quintile (>2,531 mL/day) with the lowest quintile (<1,290 mL/day) (Ptrend = 0.01). However, no association was detected when the analysis was based on recent diet or cumulative updated diet. The updated analysis for total fluid intake and bladder cancer was attenuated compared with the original findings from the first 10-year follow-up period. PMID:22355034

Candidate Loci for Yield-Related Traits in Maize Revealed by a Combination of MetaQTL Analysis and Regional Association Mapping

PubMed Central

Chen, Lin; An, Yixin; Li, Yong-xiang; Li, Chunhui; Shi, Yunsu; Song, Yanchun; Zhang, Dengfeng; Wang, Tianyu; Li, Yu

2017-01-01

Maize grain yield and related traits are complex and are controlled by a large number of genes of small effect or quantitative trait loci (QTL). Over the years, a large number of yield-related QTLs have been identified in maize and deposited in public databases. However, integrating and re-analyzing these data and mining candidate loci for yield-related traits has become a major issue in maize. In this study, we collected information on QTLs conferring maize yield-related traits from 33 published studies. Then, 999 of these QTLs were iteratively projected and subjected to meta-analysis to obtain metaQTLs (MQTLs). A total of 76 MQTLs were found across the maize genome. Based on a comparative genomics strategy, several maize orthologs of rice yield-related genes were identified in these MQTL regions. Furthermore, three potential candidate genes (Gene ID: GRMZM2G359974, GRMZM2G301884, and GRMZM2G083894) associated with kernel size and weight within three MQTL regions were identified using regional association mapping, based on the results of the meta-analysis. This strategy, combining MQTL analysis and regional association mapping, is helpful for functional marker development and rapid identification of candidate genes or loci. PMID:29312420

UPIOM: a new tool of MFA and its application to the flow of iron and steel associated with car production.

PubMed

Nakamura, Shinichiro; Kondo, Yasushi; Matsubae, Kazuyo; Nakajima, Kenichi; Nagasaka, Tetsuya

2011-02-01

Identification of the flow of materials and substances associated with a product system provides useful information for Life Cycle Analysis (LCA), and contributes to extending the scope of complementarity between LCA and Materials Flow Analysis/Substances Flow Analysis (MFA/SFA), the two major tools of industrial ecology. This paper proposes a new methodology based on input-output analysis for identifying the physical input-output flow of individual materials that is associated with the production of a unit of given product, the unit physical input-output by materials (UPIOM). While the Sankey diagram has been a standard tool for the visualization of MFA/SFA, with an increase in the complexity of the flows under consideration, which will be the case when economy-wide intersectoral flows of materials are involved, the Sankey diagram may become too complex for effective visualization. An alternative way to visually represent material flows is proposed which makes use of triangulation of the flow matrix based on degrees of fabrication. The proposed methodology is applied to the flow of pig iron and iron and steel scrap that are associated with the production of a passenger car in Japan. Its usefulness to identify a specific MFA pattern from the original IO table is demonstrated.

Tobacco, Marijuana, and Alcohol Use in University Students: A Cluster Analysis

PubMed Central

Primack, Brian A.; Kim, Kevin H.; Shensa, Ariel; Sidani, Jaime E.; Barnett, Tracey E.; Switzer, Galen E.

2012-01-01

Objective Segmentation of populations may facilitate development of targeted substance abuse prevention programs. We aimed to partition a national sample of university students according to profiles based on substance use. Participants We used 2008–2009 data from the National College Health Assessment from the American College Health Association. Our sample consisted of 111,245 individuals from 158 institutions. Method We partitioned the sample using cluster analysis according to current substance use behaviors. We examined the association of cluster membership with individual and institutional characteristics. Results Cluster analysis yielded six distinct clusters. Three individual factors—gender, year in school, and fraternity/sorority membership—were the most strongly associated with cluster membership. Conclusions In a large sample of university students, we were able to identify six distinct patterns of substance abuse. It may be valuable to target specific populations of college-aged substance users based on individual factors. However, comprehensive intervention will require a multifaceted approach. PMID:22686360

Correlates of home and neighbourhood-based physical activity in UK 3–4-year-old children

PubMed Central

Hesketh, Kathryn R.; van Sluijs, Esther M.F.

2016-01-01

Background: Identifying context-specific correlates of home- and neighbourhood-based physical activity in preschool-aged children may help improve intervention program development for these settings. Methods: A total of 153 3–4-year-old children were recruited through preschool settings in Cambridgeshire (January–July 2013). Children wore Actiheart accelerometers for ≤7 days to assess their sedentary time (ST), light-(LPA) and moderate- to vigorous-intensity physical activity (MVPA). A parent-completed questionnaire assessed correlates across the ecological model and the child’s preschool attendance during the measurement week. Only accelerometer data for times when children were at home were used. Multilevel models (Level 1: days; Level 2: child) examined associations between maternal-reported exposure variables and each outcome (children’s home- and neighbourhood-based ST, LPA and MVPA) (main analysis). Further analyses included the subsample of children with complete paternal correlates data (father analysis). Results: In the main analyses, children with older siblings engaged in less ST. Children whose mothers reported being ‘moderately inactive’ or ‘active’ (vs. inactive) engaged in less LPA, while children whose mothers worked >35 h week−1 engaged in less MVPA. More equipment at home was associated with lower LPA but greater MVPA. In the father analysis, father’s television viewing before 6 pm was associated with greater ST and less MVPA in children; the negative association between mother’s activity and children’s LPA was retained. Conclusion: Family demographics and parental behaviours appear to have the strongest association with children’s home- and neighbourhood-based ST, LPA and MVPA. This study further highlights the importance of examining both maternal and paternal behaviours. PMID:27175002

A genome-wide approach to children's aggressive behavior: The EAGLE consortium.

PubMed

Pappa, Irene; St Pourcain, Beate; Benke, Kelly; Cavadino, Alana; Hakulinen, Christian; Nivard, Michel G; Nolte, Ilja M; Tiesler, Carla M T; Bakermans-Kranenburg, Marian J; Davies, Gareth E; Evans, David M; Geoffroy, Marie-Claude; Grallert, Harald; Groen-Blokhuis, Maria M; Hudziak, James J; Kemp, John P; Keltikangas-Järvinen, Liisa; McMahon, George; Mileva-Seitz, Viara R; Motazedi, Ehsan; Power, Christine; Raitakari, Olli T; Ring, Susan M; Rivadeneira, Fernando; Rodriguez, Alina; Scheet, Paul A; Seppälä, Ilkka; Snieder, Harold; Standl, Marie; Thiering, Elisabeth; Timpson, Nicholas J; Veenstra, René; Velders, Fleur P; Whitehouse, Andrew J O; Smith, George Davey; Heinrich, Joachim; Hypponen, Elina; Lehtimäki, Terho; Middeldorp, Christel M; Oldehinkel, Albertine J; Pennell, Craig E; Boomsma, Dorret I; Tiemeier, Henning

2016-07-01

Individual differences in aggressive behavior emerge in early childhood and predict persisting behavioral problems and disorders. Studies of antisocial and severe aggression in adulthood indicate substantial underlying biology. However, little attention has been given to genome-wide approaches of aggressive behavior in children. We analyzed data from nine population-based studies and assessed aggressive behavior using well-validated parent-reported questionnaires. This is the largest sample exploring children's aggressive behavior to date (N = 18,988), with measures in two developmental stages (N = 15,668 early childhood and N = 16,311 middle childhood/early adolescence). First, we estimated the additive genetic variance of children's aggressive behavior based on genome-wide SNP information, using genome-wide complex trait analysis (GCTA). Second, genetic associations within each study were assessed using a quasi-Poisson regression approach, capturing the highly right-skewed distribution of aggressive behavior. Third, we performed meta-analyses of genome-wide associations for both the total age-mixed sample and the two developmental stages. Finally, we performed a gene-based test using the summary statistics of the total sample. GCTA quantified variance tagged by common SNPs (10-54%). The meta-analysis of the total sample identified one region in chromosome 2 (2p12) at near genome-wide significance (top SNP rs11126630, P = 5.30 × 10(-8) ). The separate meta-analyses of the two developmental stages revealed suggestive evidence of association at the same locus. The gene-based analysis indicated association of variation within AVPR1A with aggressive behavior. We conclude that common variants at 2p12 show suggestive evidence for association with childhood aggression. Replication of these initial findings is needed, and further studies should clarify its biological meaning. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Comprehensive gene- and pathway-based analysis of depressive symptoms in older adults.

PubMed

Nho, Kwangsik; Ramanan, Vijay K; Horgusluoglu, Emrin; Kim, Sungeun; Inlow, Mark H; Risacher, Shannon L; McDonald, Brenna C; Farlow, Martin R; Foroud, Tatiana M; Gao, Sujuan; Callahan, Christopher M; Hendrie, Hugh C; Niculescu, Alexander B; Saykin, Andrew J

2015-01-01

Depressive symptoms are common in older adults and are particularly prevalent in those with or at elevated risk for dementia. Although the heritability of depression is estimated to be substantial, single nucleotide polymorphism-based genome-wide association studies of depressive symptoms have had limited success. In this study, we performed genome-wide gene- and pathway-based analyses of depressive symptom burden. Study participants included non-Hispanic Caucasian subjects (n = 6,884) from three independent cohorts, the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Health and Retirement Study (HRS), and the Indiana Memory and Aging Study (IMAS). Gene-based meta-analysis identified genome-wide significant associations (ANGPT4 and FAM110A, q-value = 0.026; GRM7-AS3 and LRFN5, q-value = 0.042). Pathway analysis revealed enrichment of association in 105 pathways, including multiple pathways related to ERK/MAPK signaling, GSK3 signaling in bipolar disorder, cell development, and immune activation and inflammation. GRM7, ANGPT4, and LRFN5 have been previously implicated in psychiatric disorders, including the GRM7 region displaying association with major depressive disorder. The ERK/MAPK signaling pathway is a known target of antidepressant drugs and has important roles in neuronal plasticity, and GSK3 signaling has been previously implicated in Alzheimer's disease and as a promising therapeutic target for depression. Our results warrant further investigation in independent and larger cohorts and add to the growing understanding of the genetics and pathobiology of depressive symptoms in aging and neurodegenerative disorders. In particular, the genes and pathways demonstrating association with depressive symptoms may be potential therapeutic targets for these symptoms in older adults.

Retrospective Binary-Trait Association Test Elucidates Genetic Architecture of Crohn Disease

PubMed Central

Jiang, Duo; Zhong, Sheng; McPeek, Mary Sara

2016-01-01

In genetic association testing, failure to properly control for population structure can lead to severely inflated type 1 error and power loss. Meanwhile, adjustment for relevant covariates is often desirable and sometimes necessary to protect against spurious association and to improve power. Many recent methods to account for population structure and covariates are based on linear mixed models (LMMs), which are primarily designed for quantitative traits. For binary traits, however, LMM is a misspecified model and can lead to deteriorated performance. We propose CARAT, a binary-trait association testing approach based on a mixed-effects quasi-likelihood framework, which exploits the dichotomous nature of the trait and achieves computational efficiency through estimating equations. We show in simulation studies that CARAT consistently outperforms existing methods and maintains high power in a wide range of population structure settings and trait models. Furthermore, CARAT is based on a retrospective approach, which is robust to misspecification of the phenotype model. We apply our approach to a genome-wide analysis of Crohn disease, in which we replicate association with 17 previously identified regions. Moreover, our analysis on 5p13.1, an extensively reported region of association, shows evidence for the presence of multiple independent association signals in the region. This example shows how CARAT can leverage known disease risk factors to shed light on the genetic architecture of complex traits. PMID:26833331

Rare-Variant Association Analysis: Study Designs and Statistical Tests

PubMed Central

Lee, Seunggeung; Abecasis, Gonçalo R.; Boehnke, Michael; Lin, Xihong

2014-01-01

Despite the extensive discovery of trait- and disease-associated common variants, much of the genetic contribution to complex traits remains unexplained. Rare variants can explain additional disease risk or trait variability. An increasing number of studies are underway to identify trait- and disease-associated rare variants. In this review, we provide an overview of statistical issues in rare-variant association studies with a focus on study designs and statistical tests. We present the design and analysis pipeline of rare-variant studies and review cost-effective sequencing designs and genotyping platforms. We compare various gene- or region-based association tests, including burden tests, variance-component tests, and combined omnibus tests, in terms of their assumptions and performance. Also discussed are the related topics of meta-analysis, population-stratification adjustment, genotype imputation, follow-up studies, and heritability due to rare variants. We provide guidelines for analysis and discuss some of the challenges inherent in these studies and future research directions. PMID:24995866

Coexpression network analysis identifies transcriptional modules associated with genomic alterations in neuroblastoma.

PubMed

Yang, Liulin; Li, Yun; Wei, Zhi; Chang, Xiao

2018-06-01

Neuroblastoma is a highly complex and heterogeneous cancer in children. Acquired genomic alterations including MYCN amplification, 1p deletion and 11q deletion are important risk factors and biomarkers in neuroblastoma. Here, we performed a co-expression-based gene network analysis to study the intrinsic association between specific genomic changes and transcriptome organization. We identified multiple gene coexpression modules which are recurrent in two independent datasets and associated with functional pathways including nervous system development, cell cycle, immune system process and extracellular matrix/space. Our results also indicated that modules involved in nervous system development and cell cycle are highly associated with MYCN amplification and 1p deletion, while modules responding to immune system process are associated with MYCN amplification only. In summary, this integrated analysis provides novel insights into molecular heterogeneity and pathogenesis of neuroblastoma. This article is part of a Special Issue entitled: Accelerating Precision Medicine through Genetic and Genomic Big Data Analysis edited by Yudong Cai & Tao Huang. Copyright © 2017. Published by Elsevier B.V.

Identification of key regulators of pancreatic cancer progression through multidimensional systems-level analysis.

PubMed

Rajamani, Deepa; Bhasin, Manoj K

2016-05-03

Pancreatic cancer is an aggressive cancer with dismal prognosis, urgently necessitating better biomarkers to improve therapeutic options and early diagnosis. Traditional approaches of biomarker detection that consider only one aspect of the biological continuum like gene expression alone are limited in their scope and lack robustness in identifying the key regulators of the disease. We have adopted a multidimensional approach involving the cross-talk between the omics spaces to identify key regulators of disease progression. Multidimensional domain-specific disease signatures were obtained using rank-based meta-analysis of individual omics profiles (mRNA, miRNA, DNA methylation) related to pancreatic ductal adenocarcinoma (PDAC). These domain-specific PDAC signatures were integrated to identify genes that were affected across multiple dimensions of omics space in PDAC (genes under multiple regulatory controls, GMCs). To further pin down the regulators of PDAC pathophysiology, a systems-level network was generated from knowledge-based interaction information applied to the above identified GMCs. Key regulators were identified from the GMC network based on network statistics and their functional importance was validated using gene set enrichment analysis and survival analysis. Rank-based meta-analysis identified 5391 genes, 109 miRNAs and 2081 methylation-sites significantly differentially expressed in PDAC (false discovery rate ≤ 0.05). Bimodal integration of meta-analysis signatures revealed 1150 and 715 genes regulated by miRNAs and methylation, respectively. Further analysis identified 189 altered genes that are commonly regulated by miRNA and methylation, hence considered GMCs. Systems-level analysis of the scale-free GMCs network identified eight potential key regulator hubs, namely E2F3, HMGA2, RASA1, IRS1, NUAK1, ACTN1, SKI and DLL1, associated with important pathways driving cancer progression. Survival analysis on individual key regulators revealed that higher expression of IRS1 and DLL1 and lower expression of HMGA2, ACTN1 and SKI were associated with better survival probabilities. It is evident from the results that our hierarchical systems-level multidimensional analysis approach has been successful in isolating the converging regulatory modules and associated key regulatory molecules that are potential biomarkers for pancreatic cancer progression.

SimHap GUI: An intuitive graphical user interface for genetic association analysis

PubMed Central

Carter, Kim W; McCaskie, Pamela A; Palmer, Lyle J

2008-01-01

Background Researchers wishing to conduct genetic association analysis involving single nucleotide polymorphisms (SNPs) or haplotypes are often confronted with the lack of user-friendly graphical analysis tools, requiring sophisticated statistical and informatics expertise to perform relatively straightforward tasks. Tools, such as the SimHap package for the R statistics language, provide the necessary statistical operations to conduct sophisticated genetic analysis, but lacks a graphical user interface that allows anyone but a professional statistician to effectively utilise the tool. Results We have developed SimHap GUI, a cross-platform integrated graphical analysis tool for conducting epidemiological, single SNP and haplotype-based association analysis. SimHap GUI features a novel workflow interface that guides the user through each logical step of the analysis process, making it accessible to both novice and advanced users. This tool provides a seamless interface to the SimHap R package, while providing enhanced functionality such as sophisticated data checking, automated data conversion, and real-time estimations of haplotype simulation progress. Conclusion SimHap GUI provides a novel, easy-to-use, cross-platform solution for conducting a range of genetic and non-genetic association analyses. This provides a free alternative to commercial statistics packages that is specifically designed for genetic association analysis. PMID:19109877

Candidate genetic pathways for attention-deficit/hyperactivity disorder (ADHD) show association to hyperactive/impulsive symptoms in children with ADHD.

PubMed

Bralten, Janita; Franke, Barbara; Waldman, Irwin; Rommelse, Nanda; Hartman, Catharina; Asherson, Philip; Banaschewski, Tobias; Ebstein, Richard P; Gill, Michael; Miranda, Ana; Oades, Robert D; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph A; Oosterlaan, Jaap; Sonuga-Barke, Edmund; Steinhausen, Hans-Christoph; Faraone, Stephen V; Buitelaar, Jan K; Arias-Vásquez, Alejandro

2013-11-01

Because multiple genes with small effect sizes are assumed to play a role in attention-deficit/hyperactivity disorder (ADHD) etiology, considering multiple variants within the same analysis likely increases the total explained phenotypic variance, thereby boosting the power of genetic studies. This study investigated whether pathway-based analysis could bring scientists closer to unraveling the biology of ADHD. The pathway was described as a predefined gene selection based on a well-established database or literature data. Common genetic variants in pathways involved in dopamine/norepinephrine and serotonin neurotransmission and genes involved in neuritic outgrowth were investigated in cases from the International Multicentre ADHD Genetics (IMAGE) study. Multivariable analysis was performed to combine the effects of single genetic variants within the pathway genes. Phenotypes were DSM-IV symptom counts for inattention and hyperactivity/impulsivity (n = 871) and symptom severity measured with the Conners Parent (n = 930) and Teacher (n = 916) Rating Scales. Summing genetic effects of common genetic variants within the pathways showed a significant association with hyperactive/impulsive symptoms ((p)empirical = .007) but not with inattentive symptoms ((p)empirical = .73). Analysis of parent-rated Conners hyperactive/impulsive symptom scores validated this result ((p)empirical = .0018). Teacher-rated Conners scores were not associated. Post hoc analyses showed a significant contribution of all pathways to the hyperactive/impulsive symptom domain (dopamine/norepinephrine, (p)empirical = .0004; serotonin, (p)empirical = .0149; neuritic outgrowth, (p)empirical = .0452). The present analysis shows an association between common variants in 3 genetic pathways and the hyperactive/impulsive component of ADHD. This study demonstrates that pathway-based association analyses, using quantitative measurements of ADHD symptom domains, can increase the power of genetic analyses to identify biological risk factors involved in this disorder. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

A System-Level Pathway-Phenotype Association Analysis Using Synthetic Feature Random Forest

PubMed Central

Pan, Qinxin; Hu, Ting; Malley, James D.; Andrew, Angeline S.; Karagas, Margaret R.; Moore, Jason H.

2015-01-01

As the cost of genome-wide genotyping decreases, the number of genome-wide association studies (GWAS) has increased considerably. However, the transition from GWAS findings to the underlying biology of various phenotypes remains challenging. As a result, due to its system-level interpretability, pathway analysis has become a popular tool for gaining insights on the underlying biology from high-throughput genetic association data. In pathway analyses, gene sets representing particular biological processes are tested for significant associations with a given phenotype. Most existing pathway analysis approaches rely on single-marker statistics and assume that pathways are independent of each other. As biological systems are driven by complex biomolecular interactions, embracing the complex relationships between single-nucleotide polymorphisms (SNPs) and pathways needs to be addressed. To incorporate the complexity of gene-gene interactions and pathway-pathway relationships, we propose a system-level pathway analysis approach, synthetic feature random forest (SF-RF), which is designed to detect pathway-phenotype associations without making assumptions about the relationships among SNPs or pathways. In our approach, the genotypes of SNPs in a particular pathway are aggregated into a synthetic feature representing that pathway via Random Forest (RF). Multiple synthetic features are analyzed using RF simultaneously and the significance of a synthetic feature indicates the significance of the corresponding pathway. We further complement SF-RF with pathway-based Statistical Epistasis Network (SEN) analysis that evaluates interactions among pathways. By investigating the pathway SEN, we hope to gain additional insights into the genetic mechanisms contributing to the pathway-phenotype association. We apply SF-RF to a population-based genetic study of bladder cancer and further investigate the mechanisms that help explain the pathway-phenotype associations using SEN. The bladder cancer associated pathways we found are both consistent with existing biological knowledge and reveal novel and plausible hypotheses for future biological validations. PMID:24535726

Cost effectiveness of universal umbilical cord blood gas and lactate analysis in a tertiary level maternity unit.

PubMed

White, Christopher R H; Doherty, Dorota A; Cannon, Jeffrey W; Kohan, Rolland; Newnham, John P; Pennell, Craig E

2016-07-01

There is an increasing body of literature supporting universal umbilical cord blood gas analysis (UCBGA) into all maternity units. A significant impediment to UCBGA's introduction is the perceived expense of the introduction and associated ongoing costs. Consequently, this study set out to conduct the first cost-effectiveness analysis of introducing universal UCBGA. Analysis was based on 42,100 consecutive deliveries ≥23 weeks of gestation at a single tertiary obstetric unit. Within 4 years of UCBGA's introduction there was a 45% reduction in term special care nursery (SCN) admissions >2499 g. Incurred costs included initial and ongoing costs associated with universal UCBGA. Averted costs were based on local diagnosis-related grouping costs for reduction in term SCN admissions. Incremental cost-effectiveness ratio (ICER) and sensitivity analysis results were reported. Under the base-case scenario, the adoption of universal UCBGA was less costly and more effective than selective UCBGA over 4 years and resulted in saving of AU$641,532 while adverting 376 SCN admissions. Sensitivity analysis showed that UCBGA was cost-effective in 51.8%, 83.3%, 99.6% and 100% of simulations in years 1, 2, 3 and 4. These conclusions were not sensitive to wide, clinically possible variations in parameter values for neonatal intensive care unit and SCN admissions, magnitude of averted SCN admissions, cumulative delivery numbers, and SCN admission costs. Universal UCBGA is associated with significant initial and ongoing costs; however, potential averted costs (due to reduced SCN admissions) exceed incurred costs in most scenarios.

Study protocol for examining job strain as a risk factor for severe unipolar depression in an individual participant meta-analysis of 14 European cohorts.

PubMed

Madsen, Ida E H; Hannerz, Harald; Nyberg, Solja T; Magnusson Hanson, Linda L; Ahola, Kirsi; Alfredsson, Lars; Batty, G David; Bjorner, Jakob B; Borritz, Marianne; Burr, Hermann; Dragano, Nico; Ferrie, Jane E; Hamer, Mark; Jokela, Markus; Knutsson, Anders; Koskenvuo, Markku; Koskinen, Aki; Leineweber, Constanze; Nielsen, Martin L; Nordin, Maria; Oksanen, Tuula; Pejtersen, Jan H; Pentti, Jaana; Salo, Paula; Singh-Manoux, Archana; Suominen, Sakari; Theorell, Töres; Toppinen-Tanner, Salla; Vahtera, Jussi; Väänänen, Ari; Westerholm, Peter J M; Westerlund, Hugo; Fransson, Eleonor; Heikkilä, Katriina; Virtanen, Marianna; Rugulies, Reiner; Kivimäki, Mika

2013-01-01

Previous studies have shown that gainfully employed individuals with high work demands and low control at work (denoted "job strain") are at increased risk of common mental disorders, including depression. Most existing studies have, however, measured depression using self-rated symptom scales that do not necessarily correspond to clinically diagnosed depression. In addition, a meta-analysis from 2008 indicated publication bias in the field.   This study protocol describes the planned design and analyses of an individual participant data meta-analysis, to examine whether job strain is associated with an increased risk of clinically diagnosed unipolar depression based on hospital treatment registers.  The study will be based on data from approximately 120,000 individuals who participated in 14 studies on work environment and health in 4 European countries. The self-reported working conditions data will be merged with national registers on psychiatric hospital treatment, primarily hospital admissions. Study-specific risk estimates for the association between job strain and depression will be calculated using Cox regressions. The study-specific risk estimates will be pooled using random effects meta-analysis.   The planned analyses will help clarify whether job strain is associated with an increased risk of clinically diagnosed unipolar depression. As the analysis is based on pre-planned study protocols and an individual participant data meta-analysis, the pooled risk estimates will not be influenced by selective reporting and publication bias. However, the results of the planned study may only pertain to severe cases of unipolar depression, because of the outcome measure applied.

An evidence-based analysis of epidemiologic associations between lymphatic and hematopoietic cancers and occupational exposure to gasoline.

PubMed

Keenan, J J; Gaffney, S; Gross, S A; Ronk, C J; Paustenbach, D J; Galbraith, D; Kerger, B D

2013-10-01

The presence of benzene in motor gasoline has been a health concern for potential increased risk of acute myelogenous leukemia and perhaps other lymphatic/hematopoietic cancers for approximately 40 years. Because of the widespread and increasing use of gasoline by consumers and the high exposure potential of occupational cohorts, a thorough understanding of this issue is important. The current study utilizes an evidence-based approach to examine whether or not the available epidemiologic studies demonstrate a strong and consistent association between occupational exposure to gasoline and lymphatic/hematopoietic cancers. Among 67 epidemiologic studies initially identified, 54 were ranked according to specific criteria relating to the relevance and robustness of each study for answering the research question. The 30 highest-ranked studies were sorted into three tiers of evidence and were analyzed for strength, specificity, consistency, temporality, dose-response trends and coherence. Meta statistics were also calculated for each general and specific lymphatic/hematopoietic cancer category with adequate data. The evidence-based analysis did not confirm any strong and consistent association between occupational exposure to gasoline and lymphatic/hematopoietic cancers based on the epidemiologic studies available to date. These epidemiologic findings, combined with the evidence showing relatively low occupational benzene vapor exposures associated with gasoline formulations during the last three decades, suggest that current motor gasoline formulations are not associated with increased lymphatic/hematopoietic cancer risks related to benzene.

A Population-Based Study of Gastroesophageal Reflux Disease and Sleep Problems in Elderly Twins

PubMed Central

Lindam, Anna; Jansson, Catarina; Nordenstedt, Helena; Pedersen, Nancy L.; Lagergren, Jesper

2012-01-01

Background & Aims Previous studies indicate an association between sleep problems and gastroesophageal reflux disease (GERD). Although both these conditions separately have moderate heritabilities, confounding by genetic factors has not previously been taken into account. This study aimed to reveal the association between sleep problems and GERD, while adjusting for heredity and other potential confounding factors. Methods This cross-sectional population-based study included all 8,014 same-sexed twins of at least 65 years of age and born in Sweden between 1886 and 1958, who participated in telephone interviews in 1998–2002. Three logistic regression models were used 1) external control analysis, 2) within-pair co-twin analysis with dizygotic (DZ) twin pairs discordant for GERD, and 3) within-pair co-twin analysis with monozygotic (MZ) twin pairs discordant for GERD. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and adjusted for established risk factors for GERD, i.e. sex, age, body mass index (BMI), tobacco smoking, and educational level. Results A dose-response association was identified between increasing levels of sleep problems and GERD in the external control analysis. Individuals who often experienced sleep problems had a two-fold increased occurrence of GERD compared to those who seldom had sleep problems (OR 2.0, 95% CI 1.8–2.4). The corresponding association was of similar strength in the co-twin analysis including 356 DZ pairs (OR 2.2, 95% CI 1.6–3.4), and in the co-twin analysis including 210 MZ pairs (OR 1.5, 95% CI 0.9–2.7). Conclusion A dose-dependent association between sleep problems and GERD remains after taking heredity and other known risk factors for GERD into account. PMID:23119069

A Serological Biopsy Using Five Stomach-Specific Circulating Biomarkers for Gastric Cancer Risk Assessment: A Multi-Phase Study.

PubMed

Tu, Huakang; Sun, Liping; Dong, Xiao; Gong, Yuehua; Xu, Qian; Jing, Jingjing; Bostick, Roberd M; Wu, Xifeng; Yuan, Yuan

2017-05-01

We aimed to assess a serological biopsy using five stomach-specific circulating biomarkers-pepsinogen I (PGI), PGII, PGI/II ratio, anti-Helicobacter pylori (H. pylori) antibody, and gastrin-17 (G-17)-for identifying high-risk individuals and predicting risk of developing gastric cancer (GC). Among 12,112 participants with prospective follow-up from an ongoing population-based screening program using both serology and gastroscopy in China, we conducted a multi-phase study involving a cross-sectional analysis, a follow-up analysis, and an integrative risk prediction modeling analysis. In the cross-sectional analysis, the five biomarkers (especially PGII, the PGI/II ratio, and H. pylori sero-positivity) were associated with the presence of precancerous gastric lesions or GC at enrollment. In the follow-up analysis, low PGI levels and PGI/II ratios were associated with higher risk of developing GC, and both low (<0.5 pmol/l) and high (>4.7 pmol/l) G-17 levels were associated with higher risk of developing GC, suggesting a J-shaped association. In the risk prediction modeling analysis, the five biomarkers combined yielded a C statistic of 0.803 (95% confidence interval (CI)=0.789-0.816) and improved prediction beyond traditional risk factors (C statistic from 0.580 to 0.811, P<0.001) for identifying precancerous lesions at enrollment, and higher serological biopsy scores based on the five biomarkers at enrollment were associated with higher risk of developing GC during follow-up (P for trend <0.001). A serological biopsy composed of the five stomach-specific circulating biomarkers could be used to identify high-risk individuals for further diagnostic gastroscopy, and to stratify individuals' risk of developing GC and thus to guide targeted screening and precision prevention.

SNPassoc: an R package to perform whole genome association studies.

PubMed

González, Juan R; Armengol, Lluís; Solé, Xavier; Guinó, Elisabet; Mercader, Josep M; Estivill, Xavier; Moreno, Víctor

2007-03-01

The popularization of large-scale genotyping projects has led to the widespread adoption of genetic association studies as the tool of choice in the search for single nucleotide polymorphisms (SNPs) underlying susceptibility to complex diseases. Although the analysis of individual SNPs is a relatively trivial task, when the number is large and multiple genetic models need to be explored it becomes necessary a tool to automate the analyses. In order to address this issue, we developed SNPassoc, an R package to carry out most common analyses in whole genome association studies. These analyses include descriptive statistics and exploratory analysis of missing values, calculation of Hardy-Weinberg equilibrium, analysis of association based on generalized linear models (either for quantitative or binary traits), and analysis of multiple SNPs (haplotype and epistasis analysis). Package SNPassoc is available at CRAN from http://cran.r-project.org. A tutorial is available on Bioinformatics online and in http://davinci.crg.es/estivill_lab/snpassoc.

Does the impact of a plant-based diet during pregnancy on birth weight differ by ethnicity? A dietary pattern analysis from a prospective Canadian birth cohort alliance.

PubMed

Zulyniak, Michael A; de Souza, Russell J; Shaikh, Mateen; Desai, Dipika; Lefebvre, Diana L; Gupta, Milan; Wilson, Julie; Wahi, Gita; Subbarao, Padmaja; Becker, Allan B; Mandhane, Piush; Turvey, Stuart E; Beyene, Joseph; Atkinson, Stephanie; Morrison, Katherine M; McDonald, Sarah; Teo, Koon K; Sears, Malcolm R; Anand, Sonia S

2017-11-14

Birth weight is an indicator of newborn health and a strong predictor of health outcomes in later life. Significant variation in diet during pregnancy between ethnic groups in high-income countries provides an ideal opportunity to investigate the influence of maternal diet on birth weight. Four multiethnic birth cohorts based in Canada (the NutriGen Alliance). 3997 full-term mother-infant pairs of diverse ethnic groups who had principal component analysis-derived diet pattern scores-plant-based, Western and health-conscious-and birth weight data. No associations were identified between the Western and health-conscious diet patterns and birth weight; however, the plant-based dietary pattern was inversely associated with birth weight (β=-67.6 g per 1-unit increase; P<0.001), and an interaction with non-white ethnicity and birth weight was observed. Ethnically stratified analyses demonstrated that among white Europeans, maternal consumption of a plant-based diet associated with lower birth weight (β=-65.9 g per 1-unit increase; P<0.001), increased risk of small-for-gestational age (SGA; OR=1.46; 95% CI 1.08 to 1.54;P=0.005) and reduced risk of large-for-gestational age (LGA; OR=0.71; 95% CI 0.53 to 0.95;P=0.02). Among South Asians, maternal consumption of a plant-based diet associated with a higher birth weight (β=+40.5 g per 1-unit increase; P=0.01), partially explained by cooked vegetable consumption. Maternal consumption of a plant-based diet during pregnancy is associated with birth weight. Among white Europeans, a plant-based diet is associated with lower birth weight, reduced odds of an infant born LGA and increased odds of SGA, whereas among South Asians living in Canada, a plant-based diet is associated with increased birth weight. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A novel scoring system for gastric cancer risk assessment based on the expression of three CLIP4 DNA methylation-associated genes

PubMed Central

Hu, Chenggong; Zhou, Yongfang; Liu, Chang; Kang, Yan

2018-01-01

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-associated mortality worldwide. In the current study, comprehensive bioinformatic analyses were performed to develop a novel scoring system for GC risk assessment based on CAP-Gly domain containing linker protein family member 4 (CLIP4) DNA methylation status. Two GC datasets with methylation sequencing information and mRNA expression profiling were downloaded from the The Cancer Genome Atlas and Gene Expression Omnibus databases. Differentially expressed genes (DEGs) between the CLIP4 hypermethylation and CLIP4 hypomethylation groups were screened using the limma package in R 3.3.1, and survival analysis of these DEGs was performed using the survival package. A risk scoring system was established via regression factor-weighted gene expression based on linear combination to screen the most important genes associated with CLIP4 methylation and prognosis. Genes associated with high/low-risk value were selected using the limma package. Functional enrichment analysis of the top 500 DEGs that positively and negatively associated with risk values was performed using DAVID 6.8 online and the gene set enrichment analysis (GSEA) software. In total, 35 genes were identified to be that significantly associated with prognosis and CLIP4 DNA methylation, and three prognostic signature genes, claudin-11 (CLDN11), apolipoprotein D (APOD), and chordin like 1 (CHRDL1), were used to establish a risk assessment system. The prognostic scoring system exhibited efficiency in classifying patients with different prognoses, where the low-risk groups had significantly longer overall survival times than those in the high-risk groups. CLDN11, APOD and CHRDL1 exhibited reduced expression in the hypermethylation and low-risk groups compare with the hypomethylation and high-risk groups, respectively. Multivariate Cox analysis indicated that risk value could be used as an independent prognostic factor. In functional analysis, six functional gene ontology terms and five GSEA pathways were associated with CLDN11, APOD and CHRDL1. The results established the credibility of the scoring system in this study. Additionally, these three genes, which were significantly associated with CLIP4 DNA methylation and GC risk assessment, were identified as potential prognostic biomarkers. PMID:29901187

WISARD: workbench for integrated superfast association studies for related datasets.

PubMed

Lee, Sungyoung; Choi, Sungkyoung; Qiao, Dandi; Cho, Michael; Silverman, Edwin K; Park, Taesung; Won, Sungho

2018-04-20

A Mendelian transmission produces phenotypic and genetic relatedness between family members, giving family-based analytical methods an important role in genetic epidemiological studies-from heritability estimations to genetic association analyses. With the advance in genotyping technologies, whole-genome sequence data can be utilized for genetic epidemiological studies, and family-based samples may become more useful for detecting de novo mutations. However, genetic analyses employing family-based samples usually suffer from the complexity of the computational/statistical algorithms, and certain types of family designs, such as incorporating data from extended families, have rarely been used. We present a Workbench for Integrated Superfast Association studies for Related Data (WISARD) programmed in C/C++. WISARD enables the fast and a comprehensive analysis of SNP-chip and next-generation sequencing data on extended families, with applications from designing genetic studies to summarizing analysis results. In addition, WISARD can automatically be run in a fully multithreaded manner, and the integration of R software for visualization makes it more accessible to non-experts. Comparison with existing toolsets showed that WISARD is computationally suitable for integrated analysis of related subjects, and demonstrated that WISARD outperforms existing toolsets. WISARD has also been successfully utilized to analyze the large-scale massive sequencing dataset of chronic obstructive pulmonary disease data (COPD), and we identified multiple genes associated with COPD, which demonstrates its practical value.

Transcriptome Sequencing Revealed Significant Alteration of Cortical Promoter Usage and Splicing in Schizophrenia

PubMed Central

Wu, Jing Qin; Wang, Xi; Beveridge, Natalie J.; Tooney, Paul A.; Scott, Rodney J.; Carr, Vaughan J.; Cairns, Murray J.

2012-01-01

Background While hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression. Methodology/Principal Findings The data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22) from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDR<0.05). Both types of transcriptional isoforms were exemplified by reads aligned to the neurodevelopmentally significant doublecortin-like kinase 1 (DCLK1) gene. Conclusions This study provided the first deep and un-biased analysis of schizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia. PMID:22558445

Wavelet Analysis for Wind Fields Estimation

PubMed Central

Leite, Gladeston C.; Ushizima, Daniela M.; Medeiros, Fátima N. S.; de Lima, Gilson G.

2010-01-01

Wind field analysis from synthetic aperture radar images allows the estimation of wind direction and speed based on image descriptors. In this paper, we propose a framework to automate wind direction retrieval based on wavelet decomposition associated with spectral processing. We extend existing undecimated wavelet transform approaches, by including à trous with B3 spline scaling function, in addition to other wavelet bases as Gabor and Mexican-hat. The purpose is to extract more reliable directional information, when wind speed values range from 5 to 10 ms−1. Using C-band empirical models, associated with the estimated directional information, we calculate local wind speed values and compare our results with QuikSCAT scatterometer data. The proposed approach has potential application in the evaluation of oil spills and wind farms. PMID:22219699

A hierarchical and modular approach to the discovery of robust associations in genome-wide association studies from pooled DNA samples

PubMed Central

Sebastiani, Paola; Zhao, Zhenming; Abad-Grau, Maria M; Riva, Alberto; Hartley, Stephen W; Sedgewick, Amanda E; Doria, Alessandro; Montano, Monty; Melista, Efthymia; Terry, Dellara; Perls, Thomas T; Steinberg, Martin H; Baldwin, Clinton T

2008-01-01

Background One of the challenges of the analysis of pooling-based genome wide association studies is to identify authentic associations among potentially thousands of false positive associations. Results We present a hierarchical and modular approach to the analysis of genome wide genotype data that incorporates quality control, linkage disequilibrium, physical distance and gene ontology to identify authentic associations among those found by statistical association tests. The method is developed for the allelic association analysis of pooled DNA samples, but it can be easily generalized to the analysis of individually genotyped samples. We evaluate the approach using data sets from diverse genome wide association studies including fetal hemoglobin levels in sickle cell anemia and a sample of centenarians and show that the approach is highly reproducible and allows for discovery at different levels of synthesis. Conclusion Results from the integration of Bayesian tests and other machine learning techniques with linkage disequilibrium data suggest that we do not need to use too stringent thresholds to reduce the number of false positive associations. This method yields increased power even with relatively small samples. In fact, our evaluation shows that the method can reach almost 70% sensitivity with samples of only 100 subjects. PMID:18194558

Application of hazard analysis and critical control point methodology and risk-based grading to consumer food safety surveys.

PubMed

Røssvoll, Elin Halbach; Ueland, Øydis; Hagtvedt, Therese; Jacobsen, Eivind; Lavik, Randi; Langsrud, Solveig

2012-09-01

Traditionally, consumer food safety survey responses have been classified as either "right" or "wrong" and food handling practices that are associated with high risk of infection have been treated in the same way as practices with lower risks. In this study, a risk-based method for consumer food safety surveys has been developed, and HACCP (hazard analysis and critical control point) methodology was used for selecting relevant questions. We conducted a nationally representative Web-based survey (n = 2,008), and to fit the self-reported answers we adjusted a risk-based grading system originally developed for observational studies. The results of the survey were analyzed both with the traditional "right" and "wrong" classification and with the risk-based grading system. The results using the two methods were very different. Only 5 of the 10 most frequent food handling violations were among the 10 practices associated with the highest risk. These 10 practices dealt with different aspects of heat treatment (lacking or insufficient), whereas the majority of the most frequent violations involved storing food at room temperature for too long. Use of the risk-based grading system for survey responses gave a more realistic picture of risks associated with domestic food handling practices. The method highlighted important violations and minor errors, which are performed by most people and are not associated with significant risk. Surveys built on a HACCP-based approach with risk-based grading will contribute to a better understanding of domestic food handling practices and will be of great value for targeted information and educational activities.

Regional flux analysis for discovering and quantifying anatomical changes: An application to the brain morphometry in Alzheimer's disease.

PubMed

Lorenzi, M; Ayache, N; Pennec, X

2015-07-15

In this study we introduce the regional flux analysis, a novel approach to deformation based morphometry based on the Helmholtz decomposition of deformations parameterized by stationary velocity fields. We use the scalar pressure map associated to the irrotational component of the deformation to discover the critical regions of volume change. These regions are used to consistently quantify the associated measure of volume change by the probabilistic integration of the flux of the longitudinal deformations across the boundaries. The presented framework unifies voxel-based and regional approaches, and robustly describes the volume changes at both group-wise and subject-specific level as a spatial process governed by consistently defined regions. Our experiments on the large cohorts of the ADNI dataset show that the regional flux analysis is a powerful and flexible instrument for the study of Alzheimer's disease in a wide range of scenarios: cross-sectional deformation based morphometry, longitudinal discovery and quantification of group-wise volume changes, and statistically powered and robust quantification of hippocampal and ventricular atrophy. Copyright © 2015 Elsevier Inc. All rights reserved.

Stepwise Distributed Open Innovation Contests for Software Development: Acceleration of Genome-Wide Association Analysis

PubMed Central

Hill, Andrew; Loh, Po-Ru; Bharadwaj, Ragu B.; Pons, Pascal; Shang, Jingbo; Guinan, Eva; Lakhani, Karim; Kilty, Iain

2017-01-01

Abstract Background: The association of differing genotypes with disease-related phenotypic traits offers great potential to both help identify new therapeutic targets and support stratification of patients who would gain the greatest benefit from specific drug classes. Development of low-cost genotyping and sequencing has made collecting large-scale genotyping data routine in population and therapeutic intervention studies. In addition, a range of new technologies is being used to capture numerous new and complex phenotypic descriptors. As a result, genotype and phenotype datasets have grown exponentially. Genome-wide association studies associate genotypes and phenotypes using methods such as logistic regression. As existing tools for association analysis limit the efficiency by which value can be extracted from increasing volumes of data, there is a pressing need for new software tools that can accelerate association analyses on large genotype-phenotype datasets. Results: Using open innovation (OI) and contest-based crowdsourcing, the logistic regression analysis in a leading, community-standard genetics software package (PLINK 1.07) was substantially accelerated. OI allowed us to do this in <6 months by providing rapid access to highly skilled programmers with specialized, difficult-to-find skill sets. Through a crowd-based contest a combination of computational, numeric, and algorithmic approaches was identified that accelerated the logistic regression in PLINK 1.07 by 18- to 45-fold. Combining contest-derived logistic regression code with coarse-grained parallelization, multithreading, and associated changes to data initialization code further developed through distributed innovation, we achieved an end-to-end speedup of 591-fold for a data set size of 6678 subjects by 645 863 variants, compared to PLINK 1.07's logistic regression. This represents a reduction in run time from 4.8 hours to 29 seconds. Accelerated logistic regression code developed in this project has been incorporated into the PLINK2 project. Conclusions: Using iterative competition-based OI, we have developed a new, faster implementation of logistic regression for genome-wide association studies analysis. We present lessons learned and recommendations on running a successful OI process for bioinformatics. PMID:28327993

Association between coffee or caffeine consumption and fecundity and fertility: a systematic review and dose-response meta-analysis.

PubMed

Lyngsø, Julie; Ramlau-Hansen, Cecilia Høst; Bay, Bjørn; Ingerslev, Hans Jakob; Hulman, Adam; Kesmodel, Ulrik Schiøler

2017-01-01

The aim was to investigate whether coffee or caffeine consumption is associated with reproductive endpoints among women with natural fertility (ie, time to pregnancy [TTP] and spontaneous abortion [SAB]) and among women in fertility treatment (ie, clinical pregnancy rate or live birth rate). This study was a systematic review and dose-response meta-analysis including data from case-control and cohort studies. An extensive literature search was conducted in MEDLINE and Embase, with no time and language restrictions. Also, reference lists were searched manually. Two independent reviewers assessed the manuscript quality using the Newcastle-Ottawa Scale (NOS). A two-stage dose-response meta-analysis was applied to assess a potential association between coffee/caffeine consumption and the outcomes: TTP, SAB, clinical pregnancy, and live birth. Heterogeneity between studies was assessed using Cochrane Q -test and I 2 statistics. Publication bias was assessed using Egger's regression test. The pooled results showed that coffee/caffeine consumption is associated with a significantly increased risk of SAB for 300 mg caffeine/day (relative risk [RR]: 1.37, 95% confidence interval [95% CI]: 1.19; 1.57) and for 600 mg caffeine/day (RR: 2.32, 95% CI: 1.62; 3.31). No association was found between coffee/caffeine consumption and outcomes of fertility treatment (based on two studies). No clear association was found between exposure to coffee/caffeine and natural fertility as measured by fecundability odds ratio (based on three studies) or waiting TTP (based on two studies). Results from this meta-analysis support the growing evidence of an association between coffee/caffeine intake and the risk of SAB. However, viewing the reproductive capacity in a broader perspective, there seems to be little, if any, association between coffee/caffeine consumption and fecundity. In general, results from this study are supportive of a precautionary principle advised by health organizations such as European Food Safety Authority (EFSA) and World Health Organization (WHO), although the advised limit of a maximum of two to three cups of coffee/200-300 mg caffeine per day may be too high.

Stepwise Distributed Open Innovation Contests for Software Development: Acceleration of Genome-Wide Association Analysis.

PubMed

Hill, Andrew; Loh, Po-Ru; Bharadwaj, Ragu B; Pons, Pascal; Shang, Jingbo; Guinan, Eva; Lakhani, Karim; Kilty, Iain; Jelinsky, Scott A

2017-05-01

The association of differing genotypes with disease-related phenotypic traits offers great potential to both help identify new therapeutic targets and support stratification of patients who would gain the greatest benefit from specific drug classes. Development of low-cost genotyping and sequencing has made collecting large-scale genotyping data routine in population and therapeutic intervention studies. In addition, a range of new technologies is being used to capture numerous new and complex phenotypic descriptors. As a result, genotype and phenotype datasets have grown exponentially. Genome-wide association studies associate genotypes and phenotypes using methods such as logistic regression. As existing tools for association analysis limit the efficiency by which value can be extracted from increasing volumes of data, there is a pressing need for new software tools that can accelerate association analyses on large genotype-phenotype datasets. Using open innovation (OI) and contest-based crowdsourcing, the logistic regression analysis in a leading, community-standard genetics software package (PLINK 1.07) was substantially accelerated. OI allowed us to do this in <6 months by providing rapid access to highly skilled programmers with specialized, difficult-to-find skill sets. Through a crowd-based contest a combination of computational, numeric, and algorithmic approaches was identified that accelerated the logistic regression in PLINK 1.07 by 18- to 45-fold. Combining contest-derived logistic regression code with coarse-grained parallelization, multithreading, and associated changes to data initialization code further developed through distributed innovation, we achieved an end-to-end speedup of 591-fold for a data set size of 6678 subjects by 645 863 variants, compared to PLINK 1.07's logistic regression. This represents a reduction in run time from 4.8 hours to 29 seconds. Accelerated logistic regression code developed in this project has been incorporated into the PLINK2 project. Using iterative competition-based OI, we have developed a new, faster implementation of logistic regression for genome-wide association studies analysis. We present lessons learned and recommendations on running a successful OI process for bioinformatics. © The Author 2017. Published by Oxford University Press.

Associations between STAT3 rs744166 polymorphisms and susceptibility to ulcerative colitis and Crohn's disease: a meta-analysis.

PubMed

Zhang, Jixiang; Wu, Jianhong; Peng, Xiulan; Song, Jia; Wang, Jun; Dong, Weiguo

2014-01-01

Many studies have investigated the associations between the signal transducer and activator of transcription 3 (STAT3) in the susceptibility to ulcerative colitis (UC) and Crohn's disease (CD). However, the results remain inconsistent. This meta-analysis determined the risk of STAT3 rs744166 polymorphism-conferred UC and CD susceptibility. Electronic databases, including PubMed, EMBASE and the Cochrane Library, were searched for all eligible studies that evaluated the association between STAT3 rs744166 polymorphisms with UC and CD risk up to August 21, 2014. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using fixed- or random-effects models. Twelve studies containing 10298 patients with CD, 4244 patients with UC and 11191 controls were included in this meta-analysis. The results indicated that the STAT3 rs744166 polymorphism was associated with CD and UC susceptibility (CD: GA+AA vs. GG, OR = 1.20, 95%CI, 1.11-1.30, I2 = 0%, Punadjusted<0.00001, PBonferroni<0.00005, PFDR<0.00001; UC: GA+AA vs. GG, OR = 1.21, 95%CI, 1.08-1.36, I2 = 1%, Punadjusted = 0.001, PBonferroni = 0.005, PFDR = 0.00125). In subgroup analyses by ethnicity, the significant association was found only among Caucasians. However, when grouped by age of onset, positive associations were found both among adults and children. In addition, when stratified by study design and genotyping methods, the risk of CD was significantly associated with the STAT3 rs744166 polymorphism in hospital-based and population-based groups and in SNP Array and SNPlex groups. For UC, significant associations were also found in population-based, PCR-RFLP and SNPlex groups. Moreover, these findings were sufficiently robust to withstand the Bonferroni correction and false discovery rate (FDR). This meta-analysis indicates that carriers of the STAT3 rs744166 'A' allele have a significantly greater risk of CD and UC, especially among Caucasians.

Associations between STAT3 rs744166 Polymorphisms and Susceptibility to Ulcerative Colitis and Crohn's Disease: A Meta-Analysis

PubMed Central

Peng, Xiulan; Song, Jia; Wang, Jun; Dong, Weiguo

2014-01-01

Background Many studies have investigated the associations between the signal transducer and activator of transcription 3 (STAT3) in the susceptibility to ulcerative colitis (UC) and Crohn's disease (CD). However, the results remain inconsistent. This meta-analysis determined the risk of STAT3 rs744166 polymorphism-conferred UC and CD susceptibility. Materials and Methods Electronic databases, including PubMed, EMBASE and the Cochrane Library, were searched for all eligible studies that evaluated the association between STAT3 rs744166 polymorphisms with UC and CD risk up to August 21, 2014. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using fixed- or random-effects models. Results Twelve studies containing 10298 patients with CD, 4244 patients with UC and 11191 controls were included in this meta-analysis. The results indicated that the STAT3 rs744166 polymorphism was associated with CD and UC susceptibility (CD: GA+AA vs. GG, OR = 1.20, 95%CI, 1.11–1.30, I 2 = 0%, P unadjusted<0.00001, P Bonferroni<0.00005, P FDR<0.00001; UC: GA+AA vs. GG, OR = 1.21, 95%CI, 1.08–1.36, I 2 = 1%, P unadjusted = 0.001, P Bonferroni = 0.005, P FDR = 0.00125). In subgroup analyses by ethnicity, the significant association was found only among Caucasians. However, when grouped by age of onset, positive associations were found both among adults and children. In addition, when stratified by study design and genotyping methods, the risk of CD was significantly associated with the STAT3 rs744166 polymorphism in hospital-based and population-based groups and in SNP Array and SNPlex groups. For UC, significant associations were also found in population-based, PCR-RFLP and SNPlex groups. Moreover, these findings were sufficiently robust to withstand the Bonferroni correction and false discovery rate (FDR). Conclusion This meta-analysis indicates that carriers of the STAT3 rs744166 ‘A’ allele have a significantly greater risk of CD and UC, especially among Caucasians. PMID:25286337

Association between coffee or caffeine consumption and fecundity and fertility: a systematic review and dose–response meta-analysis

PubMed Central

Lyngsø, Julie; Ramlau-Hansen, Cecilia Høst; Bay, Bjørn; Ingerslev, Hans Jakob; Hulman, Adam; Kesmodel, Ulrik Schiøler

2017-01-01

Objective The aim was to investigate whether coffee or caffeine consumption is associated with reproductive endpoints among women with natural fertility (ie, time to pregnancy [TTP] and spontaneous abortion [SAB]) and among women in fertility treatment (ie, clinical pregnancy rate or live birth rate). Design This study was a systematic review and dose–response meta-analysis including data from case–control and cohort studies. Methods An extensive literature search was conducted in MEDLINE and Embase, with no time and language restrictions. Also, reference lists were searched manually. Two independent reviewers assessed the manuscript quality using the Newcastle–Ottawa Scale (NOS). A two-stage dose–response meta-analysis was applied to assess a potential association between coffee/caffeine consumption and the outcomes: TTP, SAB, clinical pregnancy, and live birth. Heterogeneity between studies was assessed using Cochrane Q-test and I2 statistics. Publication bias was assessed using Egger’s regression test. Results The pooled results showed that coffee/caffeine consumption is associated with a significantly increased risk of SAB for 300 mg caffeine/day (relative risk [RR]: 1.37, 95% confidence interval [95% CI]: 1.19; 1.57) and for 600 mg caffeine/day (RR: 2.32, 95% CI: 1.62; 3.31). No association was found between coffee/caffeine consumption and outcomes of fertility treatment (based on two studies). No clear association was found between exposure to coffee/caffeine and natural fertility as measured by fecundability odds ratio (based on three studies) or waiting TTP (based on two studies). Conclusion Results from this meta-analysis support the growing evidence of an association between coffee/caffeine intake and the risk of SAB. However, viewing the reproductive capacity in a broader perspective, there seems to be little, if any, association between coffee/caffeine consumption and fecundity. In general, results from this study are supportive of a precautionary principle advised by health organizations such as European Food Safety Authority (EFSA) and World Health Organization (WHO), although the advised limit of a maximum of two to three cups of coffee/200–300 mg caffeine per day may be too high. PMID:29276412

Application of a faith-based integration tool to assess mental and physical health interventions.

PubMed

Saunders, Donna M; Leak, Jean; Carver, Monique E; Smith, Selina A

2017-01-01

To build on current research involving faith-based interventions (FBIs) for addressing mental and physical health, this study a) reviewed the extent to which relevant publications integrate faith concepts with health and b) initiated analysis of the degree of FBI integration with intervention outcomes. Derived from a systematic search of articles published between 2007 and 2017, 36 studies were assessed with a Faith-Based Integration Assessment Tool (FIAT) to quantify faith-health integration. Basic statistical procedures were employed to determine the association of faith-based integration with intervention outcomes. The assessed studies possessed (on average) moderate, inconsistent integration because of poor use of faith measures, and moderate, inconsistent use of faith practices. Analysis procedures for determining the effect of FBI integration on intervention outcomes were inadequate for formulating practical conclusions. Regardless of integration, interventions were associated with beneficial outcomes. To determine the link between FBI integration and intervention outcomes, additional analyses are needed.

Meta-Analysis of Group Learning Activities: Empirically Based Teaching Recommendations

ERIC Educational Resources Information Center

Tomcho, Thomas J.; Foels, Rob

2012-01-01

Teaching researchers commonly employ group-based collaborative learning approaches in Teaching of Psychology teaching activities. However, the authors know relatively little about the effectiveness of group-based activities in relation to known psychological processes associated with group dynamics. Therefore, the authors conducted a meta-analytic…

Analysis of Sleep Parameters in Patients with Obstructive Sleep Apnea Studied in a Hospital vs. a Hotel-Based Sleep Center

PubMed Central

Hutchison, Kimberly N.; Song, Yanna; Wang, Lily; Malow, Beth A.

2008-01-01

Background: Polysomnography is associated with changes in sleep architecture called the first-night effect. This effect is believed to result from sleeping in an unusual environment and the technical equipment used to study sleep. Sleep experts hope to decrease this variable by providing a more familiar, comfortable atmosphere for sleep testing through hotel-based sleep centers. In this study, we compared the sleep parameters of patients studied in our hotel-based and hospital-based sleep laboratories. Methods: We retrospectively reviewed polysomnograms completed in our hotel-based and hospital-based sleep laboratories from August 2003 to July 2005. All patients were undergoing evaluation for obstructive sleep apnea. Hospital-based patients were matched for age and apnea-hypopnea index with hotel-based patients. We compared the sleep architecture changes associated with the first-night effect in the two groups. The associated conditions and symptoms listed on the polysomnography referral forms are also compared. Results: No significant differences were detected between the two groups in sleep onset latency, sleep efficiency, REM sleep latency, total amount of slow wave sleep (NREM stages 3 and 4), arousal index, and total stage 1 sleep. Conclusions: This pilot study failed to show a difference in sleep parameters associated with the first-night effect in patients undergoing sleep studies in our hotel and hospital-based sleep laboratories. Future studies need to compare the first-night effect in different sleep disorders, preferably in multi-night recordings. Citation: Hutchison KN; Song Y; Wang L; Malow BA. Analysis of sleep parameters in patients with obstructive sleep apnea studied in a hospital vs. A hotel-based sleep center. J Clin Sleep Med 2008;4(2):119–122. PMID:18468309

SNP-based association analysis for seedling traits in durum wheat (Triticum turgidum L. durum (Desf.)).

PubMed

Sabiel, Salih A I; Huang, Sisi; Hu, Xin; Ren, Xifeng; Fu, Chunjie; Peng, Junhua; Sun, Dongfa

2017-03-01

In the present study, 150 accessions of worldwide originated durum wheat germplasm ( Triticum turgidum spp. durum ) were observed for major seedling traits and their growth. The accessions were evaluated for major seedling traits under controlled conditions of hydroponics at the 13 th , 20 th , 27 th and 34 th day-after germination. Biomass traits were measured at the 34 th day-after germination. Correlation analysis was conducted among the seedling traits and three field traits at maturity, plant height, grain weight and 1000-grain weight observed in four consecutive years. Associations of the measured seedling traits and SNP markers were analyzed based on the mixed linear model (MLM). The results indicated that highly significant genetic variation and robust heritability were found for the seedling and field mature traits. In total, 259 significant associations were detected for all the traits and four growth stages. The phenotypic variation explained (R2) by a single SNP marker is higher than 10% for most (84%) of the significant SNP markers. Forty-six SNP markers associated with multiple traits, indicating non-neglectable pleiotropy in seedling stage. The associated SNP markers could be helpful for genetic analysis of seedling traits, and marker-assisted breeding of new wheat varieties with strong seedling vigor.

PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses

PubMed Central

Purcell, Shaun ; Neale, Benjamin ; Todd-Brown, Kathe ; Thomas, Lori ; Ferreira, Manuel A. R. ; Bender, David ; Maller, Julian ; Sklar, Pamela ; de Bakker, Paul I. W. ; Daly, Mark J. ; Sham, Pak C. 

2007-01-01

Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis. PMID:17701901

Possible occurrence of paraesthesia in patients taking norethisterone: an analysis on the WHO Global Individual Case Reports database (VigiBase).

PubMed

Buccellato, Elena; Biagi, Chiara; Vaccheri, Alberto; Melis, Mauro; Montanaro, Nicola; Motola, Domenico

2013-09-01

Progestogens are widely used to treat a large number of common conditions. We aimed to investigate a potential signal concerning progestogens and paraesthesia. Data were obtained from the VigiBase, the WHO Global Individual Case Safety Reports (ICSR) database, which is maintained by the Uppsala Monitoring Centre. We collected all suspected reports of paraesthesia associated with oral progestogens, reported between January 1972 and June 2012 and classified in VigiBase according to WHO-Adverse Reaction Terminology critical term 'paraesthesia'. A disproportionality analysis was conducted using the Information Component (IC) and the standard deviation (IC025) as a measure. Out of the total number of reports collected in the VigiBase (7,332,991), paraesthesia was associated with progestogen therapy in 920 reports, coming from 22 countries. Progestogens had the highest number of suspected reports (n = 864) than the other Anatomical Therapeutic Chemical (ATC) considered. Only norethisterone was associated with paraesthesia with positive IC (0.47) and IC025 (0.02). Norethisterone-associated paraesthesia appears to be a rare outcome. However, the widespread use of progestogens in medical practice suggests that it is a complaint that can affect a large number of women. Since paraesthesia can be caused by several drugs, clinicians should consider that it may be also caused by norethisterone.

Quantum Associative Neural Network with Nonlinear Search Algorithm

NASA Astrophysics Data System (ADS)

Zhou, Rigui; Wang, Huian; Wu, Qian; Shi, Yang

2012-03-01

Based on analysis on properties of quantum linear superposition, to overcome the complexity of existing quantum associative memory which was proposed by Ventura, a new storage method for multiply patterns is proposed in this paper by constructing the quantum array with the binary decision diagrams. Also, the adoption of the nonlinear search algorithm increases the pattern recalling speed of this model which has multiply patterns to O( {log2}^{2^{n -t}} ) = O( n - t ) time complexity, where n is the number of quantum bit and t is the quantum information of the t quantum bit. Results of case analysis show that the associative neural network model proposed in this paper based on quantum learning is much better and optimized than other researchers' counterparts both in terms of avoiding the additional qubits or extraordinary initial operators, storing pattern and improving the recalling speed.

Genetic Polymorphisms of Glutathione-Related Enzymes (GSTM1, GSTT1, and GSTP1) and Schizophrenia Risk: A Meta-Analysis

PubMed Central

Kim, Su Kang; Kang, Sang Wook; Chung, Joo-Ho; Park, Hae Jeong; Cho, Kyu Bong; Park, Min-Su

2015-01-01

The association between polymorphisms of glutathione-related enzyme (GST) genes and the risk of schizophrenia has been investigated in many published studies. However, their results were inconclusive. Therefore, we performed a meta-analysis to explore the association between the GSTM1, GSTT1, and GSTP1 polymorphisms and the risk of schizophrenia. Twelve case-control studies were included in this meta-analysis. The odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Our meta-analysis results revealed that GSTM1, GSTT1, and GSTP1 polymorphisms were not related to risk of schizophrenia (p > 0.05 in each model). Further analyses based on ethnicity, GSTM polymorphism showed weak association with schizophrenia in East Asian population (OR = 1.314, 95% CI = 1.025–1.684, p = 0.031). In conclusion, our meta-analysis indicated the GSTM1 polymorphism may be the only genetic risk factor for schizophrenia in East Asian population. However, more meta-analysis with a larger sample size were needed to provide more precise evidence. PMID:26295386

Integrative analysis of GWAS, eQTLs and meQTLs data suggests that multiple gene sets are associated with bone mineral density.

PubMed

Wang, W; Huang, S; Hou, W; Liu, Y; Fan, Q; He, A; Wen, Y; Hao, J; Guo, X; Zhang, F

2017-10-01

Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data METHOD: We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients' BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05. We identified multiple gene sets associated with BMD in one or more regions, including relevant known biological gene sets such as the Reactome Circadian Clock (GSEA p-value = 1.0 × 10 -4 for LS and 2.7 × 10 -2 for femoral necks BMD in eQTLs-based GSEA) and insulin-like growth factor receptor binding (GSEA p-value = 5.0 × 10 -4 for femoral necks and 2.6 × 10 -2 for lumbar spines BMD in meQTLs-based GSEA). Our results provided novel clues for subsequent functional analysis of bone metabolism, and illustrated the benefit of integrating eQTLs and meQTLs data into pathway association analysis for genetic studies of complex human diseases. Cite this article : W. Wang, S. Huang, W. Hou, Y. Liu, Q. Fan, A. He, Y. Wen, J. Hao, X. Guo, F. Zhang. Integrative analysis of GWAS, eQTLs and meQTLs data suggests that multiple gene sets are associated with bone mineral density. Bone Joint Res 2017;6:572-576. © 2017 Wang et al.

Association study between BDNF gene variants and Mexican patients with obsessive-compulsive disorder.

PubMed

Márquez, Lidia; Camarena, Beatriz; Hernández, Sandra; Lóyzaga, Cristina; Vargas, Luis; Nicolini, Humberto

2013-11-01

Obsessive-compulsive disorder (OCD) is a psychiatric disorder whose etiology is not yet known. We investigate the role of three variants of the BDNF gene (rs6265, rs1519480 and rs7124442) by single SNP and haplotype analysis in OCD Mexican patients using a case-control and family-based association design. BDNF gene variants were genotyped in 283 control subjects, 232 OCD patients and first degree relatives of 111 OCD subjects. Single SNP analysis in case-control study showed an association between rs6265 and OCD with a high frequency of Val/Val genotype and Val allele (p=0.0001 and p=0.0001, respectively). Also, genotype and allele analysis of rs1519480 showed significant differences (p=0.0001, p=0.0001; respectively) between OCD and control groups. Haplotype analysis showed a high frequency of A-T (rs6265-rs1519480) in OCD patients compared with the control group (OR=2.06 [1.18-3.59], p=0.0093) and a low frequency of haplotype A-C in the OCD patients (OR=0.04 [0.01-0.16], p=0.000002). The family-based association study showed no significant differences in the transmission of any variant. Our study replicated the association between BDNF Val66Met gene polymorphism and OCD. Also, we found a significant association of rs1519480 in OCD patients compared with a control group, region that has never been analyzed in OCD. In conclusion, our findings suggest that BDNF gene could be related to the development of OCD. © 2013 Elsevier B.V. and ECNP. All rights reserved.

Comparability of HbA1c and lipids measured with dried blood spot versus venous samples: a systematic review and meta-analysis

PubMed Central

2014-01-01

Background Levels of haemoglobin A1c (HbA1c) and blood lipids are important determinants of risk in patients with diabetes. Standard analysis methods based upon venous blood samples can be logistically challenging in resource-poor settings where much of the diabetes epidemic is occurring. Dried blood spots (DBS) provide a simple alternative method for sample collection but the comparability of data from analyses based on DBS is not well established. Methods We conducted a systematic review and meta-analysis to define the association of findings for HbA1c and blood lipids for analyses based upon standard methods compared to DBS. The Cochrane, Embase and Medline databases were searched for relevant reports and summary regression lines were estimated. Results 705 abstracts were found by the initial electronic search with 6 further reports identified by manual review of the full papers. 16 studies provided data for one or more outcomes of interest. There was a close agreement between the results for HbA1c assays based on venous and DBS samples (DBS = 0.9858venous + 0.3809), except for assays based upon affinity chromatography. Significant adjustment was required for assays of total cholesterol (DBS = 0.6807venous + 1.151) but results for triglycerides (DBS = 0.9557venous + 0.1427) were directly comparable. Conclusions For HbA1c and selected blood lipids, assays based on DBS samples are clearly associated with assays based on standard venous samples. There are, however, significant uncertainties about the nature of these associations and there is a need for standardisation of the sample collection, transportation, storage and analysis methods before the technique can be considered mainstream. This should be a research priority because better elucidation of metabolic risks in resource poor settings, where venous sampling is infeasible, will be key to addressing the global epidemic of cardiovascular diseases. PMID:25045323

A Cross-Cancer Genetic Association Analysis of the DNA Repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast, and Colorectal Cancer.

PubMed

Scarbrough, Peter M; Weber, Rachel Palmieri; Iversen, Edwin S; Brhane, Yonathan; Amos, Christopher I; Kraft, Peter; Hung, Rayjean J; Sellers, Thomas A; Witte, John S; Pharoah, Paul; Henderson, Brian E; Gruber, Stephen B; Hunter, David J; Garber, Judy E; Joshi, Amit D; McDonnell, Kevin; Easton, Doug F; Eeles, Ros; Kote-Jarai, Zsofia; Muir, Kenneth; Doherty, Jennifer A; Schildkraut, Joellen M

2016-01-01

DNA damage is an established mediator of carcinogenesis, although genome-wide association studies (GWAS) have identified few significant loci. This cross-cancer site, pooled analysis was performed to increase the power to detect common variants of DNA repair genes associated with cancer susceptibility. We conducted a cross-cancer analysis of 60,297 single nucleotide polymorphisms, at 229 DNA repair gene regions, using data from the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Our analysis included data from 32 GWAS and 48,734 controls and 51,537 cases across five cancer sites (breast, colon, lung, ovary, and prostate). Because of the unavailability of individual data, data were analyzed at the aggregate level. Meta-analysis was performed using the Association analysis for SubSETs (ASSET) software. To test for genetic associations that might escape individual variant testing due to small effect sizes, pathway analysis of eight DNA repair pathways was performed using hierarchical modeling. We identified three susceptibility DNA repair genes, RAD51B (P < 5.09 × 10(-6)), MSH5 (P < 5.09 × 10(-6)), and BRCA2 (P = 5.70 × 10(-6)). Hierarchical modeling identified several pleiotropic associations with cancer risk in the base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination pathways. Only three susceptibility loci were identified, which had all been previously reported. In contrast, hierarchical modeling identified several pleiotropic cancer risk associations in key DNA repair pathways. Results suggest that many common variants in DNA repair genes are likely associated with cancer susceptibility through small effect sizes that do not meet stringent significance testing criteria. ©2015 American Association for Cancer Research.

Association between MTHFR C677T polymorphism and depression: a meta-analysis in the Chinese population.

PubMed

Jiang, Wei; Xu, Jun; Lu, Xiao-Jie; Sun, Yang

2016-09-01

Depression is a worldwide public health issue, and its prevalence increases each year. Although a number of studies have been conducted on the association between MTHFR C677T polymorphism and depression in China, this association remains elusive and controversial. To clarify the impact of MTHFR C677T polymorphism on the risk of depression, a meta-analysis was performed in the Chinese population. Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure and Chinese Biology Medicine through May 5, 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. A total of 13 case-control studies including 1895 patients and 1913 controls were involved in this meta-analysis. Overall, T variant of MTHFR C677T gene polymorphism was significantly associated with an increased risk of depression in the Chinese population (T vs. C: OR = 1.52, 95% CI = 1.24-1.85; TT + CT vs. CC: OR = 1.64, 95% CI = 1.16-2.30; TT vs. CC: OR = 2.19, 95% CI = 1.49-3.24; TT vs. CC + CT: OR = 1.80, 95% CI = 1.31-2.46). In subgroup analyses stratified by geographic area and source of controls, the significant results were found in population-based studies, in hospital-based studies, in North and South China. The risk conferred by MTHFR C677T polymorphism is higher in North China than in South China. In conclusion, this meta-analysis suggests that MTHFR C677T polymorphism is associated with depression in the Chinese population, but these associations vary in different geographic locations.

Carotenoids and risk of fracture: a meta-analysis of observational studies

PubMed Central

Song, Xiaochao; Zhang, Xi; Li, Xinli

2017-01-01

To quantify the association between dietary and circulating carotenoids and fracture risk, a meta-analysis was conducted by searching MEDLINE and EMBASE databases for eligible articles published before May 2016. Five prospective and 2 case-control studies with 140,265 participants and 4,324 cases were identified in our meta-analysis. Among which 5 studies assessed the association between dietary carotenoids levels and hip fracture risk, 2 studies focused on the association between circulating carotenoids levels and any fracture risk. A random-effects model was employed to summarize the risk estimations and their 95% confidence intervals (CIs). Hip fracture risk among participants with high dietary total carotenoids intake was 28% lower than that in participants with low dietary total carotenoids (OR: 0.72; 95% CI: 0.51, 1.01). A similar risk of hip fracture was found for β-carotene based on 5 studies, the summarized OR for high vs. low dietary β-carotene was 0.72 (95% CI: 0.54, 0.95). However, a significant between-study heterogeneity was found (total carotene: I2 = 59.4%, P = 0.06; β-carotene: I2 = 74.4%, P = 0.04). Other individual carotenoids did not show significant associations with hip fracture risk. Circulating carotene levels had no significant association with any fracture risk, the pooled OR (95% CI) was 0.83 (0.59, 1.17). Based on the evidence from observational studies, our meta-analysis supported the hypothesis that higher dietary total carotenoids or β-carotene intake might be potentially associated with a low risk of hip fracture, however, future well-designed prospective cohort studies and randomized controlled trials are warranted to specify the associations between carotenoids and fracture. PMID:27911854

Carotenoids and risk of fracture: a meta-analysis of observational studies.

PubMed

Xu, Jiuhong; Song, Chunli; Song, Xiaochao; Zhang, Xi; Li, Xinli

2017-01-10

To quantify the association between dietary and circulating carotenoids and fracture risk, a meta-analysis was conducted by searching MEDLINE and EMBASE databases for eligible articles published before May 2016. Five prospective and 2 case-control studies with 140,265 participants and 4,324 cases were identified in our meta-analysis. Among which 5 studies assessed the association between dietary carotenoids levels and hip fracture risk, 2 studies focused on the association between circulating carotenoids levels and any fracture risk. A random-effects model was employed to summarize the risk estimations and their 95% confidence intervals (CIs). Hip fracture risk among participants with high dietary total carotenoids intake was 28% lower than that in participants with low dietary total carotenoids (OR: 0.72; 95% CI: 0.51, 1.01). A similar risk of hip fracture was found for β-carotene based on 5 studies, the summarized OR for high vs. low dietary β-carotene was 0.72 (95% CI: 0.54, 0.95). However, a significant between-study heterogeneity was found (total carotene: I2 = 59.4%, P = 0.06; β-carotene: I2 = 74.4%, P = 0.04). Other individual carotenoids did not show significant associations with hip fracture risk. Circulating carotene levels had no significant association with any fracture risk, the pooled OR (95% CI) was 0.83 (0.59, 1.17). Based on the evidence from observational studies, our meta-analysis supported the hypothesis that higher dietary total carotenoids or β-carotene intake might be potentially associated with a low risk of hip fracture, however, future well-designed prospective cohort studies and randomized controlled trials are warranted to specify the associations between carotenoids and fracture.

Continuity of care to optimize chronic disease management in the community setting: an evidence-based analysis.

PubMed

2013-01-01

This evidence-based analysis reviews relational and management continuity of care. Relational continuity refers to the duration and quality of the relationship between the care provider and the patient. Management continuity ensures that patients receive coherent, complementary, and timely care. There are 4 components of continuity of care: duration, density, dispersion, and sequence. The objective of this evidence-based analysis was to determine if continuity of care is associated with decreased health resource utilization, improved patient outcomes, and patient satisfaction. MEDLINE, EMBASE, CINAHL, the Cochrane Library, and the Centre for Reviews and Dissemination database were searched for studies on continuity of care and chronic disease published from January 2002 until December 2011. Systematic reviews, randomized controlled trials, and observational studies were eligible if they assessed continuity of care in adults and reported health resource utilization, patient outcomes, or patient satisfaction. Eight systematic reviews and 13 observational studies were identified. The reviews concluded that there is an association between continuity of care and outcomes; however, the literature base is weak. The observational studies found that higher continuity of care was frequently associated with fewer hospitalizations and emergency department visits. Three systematic reviews reported that higher continuity of care is associated with improved patient satisfaction, especially among patients with chronic conditions. Most of the studies were retrospective cross-sectional studies of large administrative databases. The databases do not capture information on trust and confidence in the provider, which is a critical component of relational continuity of care. The definitions for the selection of patients from the databases varied across studies. There is low quality evidence that: Higher continuity of care is associated with decreased health service utilization.There is insufficient evidence on the relationship of continuity of care with disease-specific outcomes.There is an association between high continuity of care and patient satisfaction, particularly among patients with chronic diseases.

[Effect of TNF-alpha gene polymorphism on outcome of thalidomide-based regimens for multiple myeloma].

PubMed

DU, Juan; Yuan, Zhen-Gang; Zhang, Chun-Yang; Fu, Wei-Jun; Jiang, Hua; Chen, Bao-An; Hou, Jian

2009-10-01

To evaluate the effect of polymorphism at the -238 and -308 position of the TNF-alpha promotor region on the clinical outcome of thalidomide (Thal)-based regimens for the treatment of multiple myeloma (MM). The polymorphism at the -238 and -308 position of the TNF-alpha promotor region of 168 MM patients treated with Thal-based regimens were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes were tested for association with overall response by logistic regression, and survival was evaluated by univariate and multivariate analysis. In TNF-alpha -238 position, 11 (6.5%) patients had GA genotype and 1 (0.6%) AA genotype. In TNF-alpha -308 position, 19 (11.3%) had GA genotype and 1 (0.6%) AA genotype. In univariate analysis, the TNF-alpha -238 GA + AA genotypes were associated with a significantly prolonged progression free survival (PFS) (P = 0.017), and a better overall survival (OS) (P = 0.150). Multivariate COX regression analysis showed that TNF-alpha -238 polymorphic status was an independent prognostic factor for prolonged PFS (P = 0.049). The TNF-alpha -238 polymorphic status is associated with a favorable clinical outcome in MM patients treated with thalidomide-based regimen. The polymorphism status of TNF-alpha gene might be of promise for developing a more informative stratification system for MM.

Visualization-based analysis of multiple response survey data

NASA Astrophysics Data System (ADS)

Timofeeva, Anastasiia

2017-11-01

During the survey, the respondents are often allowed to tick more than one answer option for a question. Analysis and visualization of such data have difficulties because of the need for processing multiple response variables. With standard representation such as pie and bar charts, information about the association between different answer options is lost. The author proposes a visualization approach for multiple response variables based on Venn diagrams. For a more informative representation with a large number of overlapping groups it is suggested to use similarity and association matrices. Some aggregate indicators of dissimilarity (similarity) are proposed based on the determinant of the similarity matrix and the maximum eigenvalue of association matrix. The application of the proposed approaches is well illustrated by the example of the analysis of advertising sources. Intersection of sets indicates that the same consumer audience is covered by several advertising sources. This information is very important for the allocation of the advertising budget. The differences between target groups in advertising sources are of interest. To identify such differences the hypothesis of homogeneity and independence are tested. Recent approach to the problem are briefly reviewed and compared. An alternative procedure is suggested. It is based on partition of a consumer audience into pairwise disjoint subsets and includes hypothesis testing of the difference between the population proportions. It turned out to be more suitable for the real problem being solved.

The -765G>C polymorphism in the cyclooxygenase-2 gene and digestive system cancer: a meta-analysis.

PubMed

Zhao, Fen; Cao, Yue; Zhu, Hong; Huang, Min; Yi, Cheng; Huang, Ying

2014-01-01

Published data regarding associations between the -765G>C polymorphism in cyclooxygenase-2 (COX-2) gene and digestive system cancer risk have been inconclusive. The aim of this study was to comprehensively evaluate the genetic risk of the -765G>C polymorphism in the COX-2 gene for digestive system cancer. A search was performed in Pubmed, Medline (Ovid), Embase, CNKI, Weipu, Wanfang and CBM databases, covering all studies until Feb 10, 2014. Statistical analysis was performed using Revman5.2. A total of 10,814 cases and 16,174 controls in 38 case-control studies were included in this meta-analysis. The results indicated that C allele carriers (GC+CC) had a 20% increased risk of digestive system cancer when compared with the homozygote GG (odds ratio (OR)=1.20, 95% confidence interval (CI), 1.00-1.44 for GC+CC vs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers (GC+CC) in Asians (OR = 1.46, 95% CI=1.07-2.01, and p=0.02) and Africans (OR=2.12, 95% CI=1.57-2.87, and p< 0.00001), but not among Caucasians, Americans and mixed groups. For subgroup analysis by cancer type (GC+CC vs GG), significant associations were found between the -765G>C polymorphism and higher risk for gastric cancer (OR=1.64, 95% CI=1.03-2.61, and p=0.04), but not for colorectal cancer, oral cancer, esophageal cancer, and others. Regarding study design (GC+CC vs GG), no significant associations were found in then population-based case-control (PCC), hospital-based case-control (HCC) and family-based case-control (FCC) studies. This meta-analysis suggested that the -765G>C polymorphism of the COX-2 gene is a potential risk factor for digestive system cancer in Asians and Africans and gastric cancer overall.

Associations of Urinary Cotinine-Verified Active and Passive Smoking with Thyroid Function: Analysis of Population-Based Nationally Representative Data.

PubMed

Kang, Jihun; Kong, Eunhee; Choi, Jongsoon

2018-05-01

The effects of active and passive smoking on thyroid function in the Korean population have not been determined. Furthermore, related research is based on self-reported smoking status, which may be inaccurate, especially among women. The present study aimed at evaluating the association between biochemically verified smoking status and thyroid function in a nationally representative Korean population. This population-based cross-sectional study included 3404 subjects without thyroid disease who were not taking thyroid medication. Smoking status was identified using self-reported data and urinary cotinine levels. Kruskal-Wallis and Jonckheere-Terpstra trend tests were performed to evaluate the association between smoking exposure and thyroid function. Multivariate logistic regression analysis was used to estimate the effect of smoking on subclinical hypothyroidism (SCH). Biochemically verified active and passive smoking rates were 43.4% and 23.3% among men and 10.0% and 22.9% among women, respectively. Active smokers had significantly lower iodine levels than passive smokers and nonsmokers. Active smoking was associated with decreased serum thyrotropin (TSH) levels among both sexes, although only men exhibited a dose-response relationship between increasing smoking exposure and decreasing TSH levels. Passive smoking slightly decreased TSH levels, but the decrease was not statistically significant. The risk of SCH decreased with increasing smoking exposure in the multivariate-adjusted analysis (p for trend = 0.027 among men and 0.042 among women). Active and passive smoking were associated with decreasing serum TSH levels and a lower risk of SCH in a Korean population. These associations might be related to lower urinary iodine levels in active smokers.

Urbanization factors associated with childhood asthma and prematurity: a population-based analysis aged from 0 to 5 years in Taiwan by using Cox regression within a hospital cluster model.

PubMed

Lin, Sheng-Chieh; Lin, Hui-Wen

2015-04-01

Childhood asthma and premature birth are both common; however, no studies have reported urbanization association between asthma and prematurity and the duration of prematurity affect asthma development. We use Taiwan Longitudinal Health Insurance Database (LHID) to explore association between asthma and prematurity among children by using a population-based analysis. This is a retrospective cohort study with registration data derived from Taiwan LHID. We evaluated prematurely born infants and children aged <5 years (n = 532) and age-matched control patients (n = 60505) using Cox proportional hazard regression analysis within a hospital cluster model. Of the 61 037 examinees, 14 012 experienced asthma during the 5-year follow-up, including 161 (72.26 per 1000 person-years) infants and children born prematurely and 13 851 (40.27 per 1000 person-years) controls. The hazard ratio for asthma during 5-year follow-up period was 1.95 (95% confidence interval = 1.67-2.28) among children born prematurely. Boys born prematurely aged 0-2 years were associated with higher asthma rates compared with girls in non-premature and premature groups. Living in urban areas, those born prematurely were associated with higher rates of asthma compared with non-prematurity. Those born prematurely lived in northern region had higher asthma hazard ratio than other regions. Our analyses indicated that sex, age, urbanization level, and geographic region are significantly associated with prematurity and asthma. Based on cumulative asthma-free survival curve generated using the Kaplan-Meier method, infants born prematurely should be closely monitored to see if they would develop asthma until the age of 6 years.

Ontology-based literature mining and class effect analysis of adverse drug reactions associated with neuropathy-inducing drugs.

PubMed

Hur, Junguk; Özgür, Arzucan; He, Yongqun

2018-06-07

Adverse drug reactions (ADRs), also called as drug adverse events (AEs), are reported in the FDA drug labels; however, it is a big challenge to properly retrieve and analyze the ADRs and their potential relationships from textual data. Previously, we identified and ontologically modeled over 240 drugs that can induce peripheral neuropathy through mining public drug-related databases and drug labels. However, the ADR mechanisms of these drugs are still unclear. In this study, we aimed to develop an ontology-based literature mining system to identify ADRs from drug labels and to elucidate potential mechanisms of the neuropathy-inducing drugs (NIDs). We developed and applied an ontology-based SciMiner literature mining strategy to mine ADRs from the drug labels provided in the Text Analysis Conference (TAC) 2017, which included drug labels for 53 neuropathy-inducing drugs (NIDs). We identified an average of 243 ADRs per NID and constructed an ADR-ADR network, which consists of 29 ADR nodes and 149 edges, including only those ADR-ADR pairs found in at least 50% of NIDs. Comparison to the ADR-ADR network of non-NIDs revealed that the ADRs such as pruritus, pyrexia, thrombocytopenia, nervousness, asthenia, acute lymphocytic leukaemia were highly enriched in the NID network. Our ChEBI-based ontology analysis identified three benzimidazole NIDs (i.e., lansoprazole, omeprazole, and pantoprazole), which were associated with 43 ADRs. Based on ontology-based drug class effect definition, the benzimidazole drug group has a drug class effect on all of these 43 ADRs. Many of these 43 ADRs also exist in the enriched NID ADR network. Our Ontology of Adverse Events (OAE) classification further found that these 43 benzimidazole-related ADRs were distributed in many systems, primarily in behavioral and neurological, digestive, skin, and immune systems. Our study demonstrates that ontology-based literature mining and network analysis can efficiently identify and study specific group of drugs and their associated ADRs. Furthermore, our analysis of drug class effects identified 3 benzimidazole drugs sharing 43 ADRs, leading to new hypothesis generation and possible mechanism understanding of drug-induced peripheral neuropathy.

Conformational Analysis of Drug Molecules: A Practical Exercise in the Medicinal Chemistry Course

ERIC Educational Resources Information Center

Yuriev, Elizabeth; Chalmers, David; Capuano, Ben

2009-01-01

Medicinal chemistry is a specialized, scientific discipline. Computational chemistry and structure-based drug design constitute important themes in the education of medicinal chemists. This problem-based task is associated with structure-based drug design lectures. It requires students to use computational techniques to investigate conformational…

The Association between Body Mass Index and Hot Flash in Midlife Women: A Meta-analysis.

PubMed

Shobeiri, Fatemeh; Jenabi, Ensiyeh; Poorolajal, Jalal; Hazavehei, Seyyed Mohammad Mahdi

2016-04-01

The association between body mass index (BMI) and hot flash risk has not been specifically clarifies yet. This meta-analysis was, therefore, conducted to estimate the association between overweight and obesity and hot flash risk. We searched PubMed, Web of Science, and Scopus for observational studies addressing the association between BMI and hot flash until August 2015. Data were independently extracted and analyzed using 95% odds ratio (OR), and confidence intervals (CI) based on the random-effects models. We identified 2,244 references and conducted seven studies with 4,219 participants. The association between hot flash and overweight was estimated 1.13 (95% CI: 0.97-1.32) and that of obesity was estimated 1.79 (95% CI: 1.52-2.11). No evidence of heterogeneity and publication bias was observed. This meta-analysis demonstrated that, though not to a great extent, obesity does increase the risk of hot flash. The findings from this meta-analysis indicated that obesity is associated with an increased risk of hot flash. Further large prospective cohort studies are required to provide convincing evidence as to whether or not BMI is associated with an increased risk of hot flashes.

An overview of the Hadoop/MapReduce/HBase framework and its current applications in bioinformatics

PubMed Central

2010-01-01

Background Bioinformatics researchers are now confronted with analysis of ultra large-scale data sets, a problem that will only increase at an alarming rate in coming years. Recent developments in open source software, that is, the Hadoop project and associated software, provide a foundation for scaling to petabyte scale data warehouses on Linux clusters, providing fault-tolerant parallelized analysis on such data using a programming style named MapReduce. Description An overview is given of the current usage within the bioinformatics community of Hadoop, a top-level Apache Software Foundation project, and of associated open source software projects. The concepts behind Hadoop and the associated HBase project are defined, and current bioinformatics software that employ Hadoop is described. The focus is on next-generation sequencing, as the leading application area to date. Conclusions Hadoop and the MapReduce programming paradigm already have a substantial base in the bioinformatics community, especially in the field of next-generation sequencing analysis, and such use is increasing. This is due to the cost-effectiveness of Hadoop-based analysis on commodity Linux clusters, and in the cloud via data upload to cloud vendors who have implemented Hadoop/HBase; and due to the effectiveness and ease-of-use of the MapReduce method in parallelization of many data analysis algorithms. PMID:21210976

An overview of the Hadoop/MapReduce/HBase framework and its current applications in bioinformatics.

PubMed

Taylor, Ronald C

2010-12-21

Bioinformatics researchers are now confronted with analysis of ultra large-scale data sets, a problem that will only increase at an alarming rate in coming years. Recent developments in open source software, that is, the Hadoop project and associated software, provide a foundation for scaling to petabyte scale data warehouses on Linux clusters, providing fault-tolerant parallelized analysis on such data using a programming style named MapReduce. An overview is given of the current usage within the bioinformatics community of Hadoop, a top-level Apache Software Foundation project, and of associated open source software projects. The concepts behind Hadoop and the associated HBase project are defined, and current bioinformatics software that employ Hadoop is described. The focus is on next-generation sequencing, as the leading application area to date. Hadoop and the MapReduce programming paradigm already have a substantial base in the bioinformatics community, especially in the field of next-generation sequencing analysis, and such use is increasing. This is due to the cost-effectiveness of Hadoop-based analysis on commodity Linux clusters, and in the cloud via data upload to cloud vendors who have implemented Hadoop/HBase; and due to the effectiveness and ease-of-use of the MapReduce method in parallelization of many data analysis algorithms.

Proper joint analysis of summary association statistics requires the adjustment of heterogeneity in SNP coverage pattern.

PubMed

Zhang, Han; Wheeler, William; Song, Lei; Yu, Kai

2017-07-07

As meta-analysis results published by consortia of genome-wide association studies (GWASs) become increasingly available, many association summary statistics-based multi-locus tests have been developed to jointly evaluate multiple single-nucleotide polymorphisms (SNPs) to reveal novel genetic architectures of various complex traits. The validity of these approaches relies on the accurate estimate of z-score correlations at considered SNPs, which in turn requires knowledge on the set of SNPs assessed by each study participating in the meta-analysis. However, this exact SNP coverage information is usually unavailable from the meta-analysis results published by GWAS consortia. In the absence of the coverage information, researchers typically estimate the z-score correlations by making oversimplified coverage assumptions. We show through real studies that such a practice can generate highly inflated type I errors, and we demonstrate the proper way to incorporate correct coverage information into multi-locus analyses. We advocate that consortia should make SNP coverage information available when posting their meta-analysis results, and that investigators who develop analytic tools for joint analyses based on summary data should pay attention to the variation in SNP coverage and adjust for it appropriately. Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.

A genome-wide association study of autism using the Simons Simplex Collection: Does reducing phenotypic heterogeneity in autism increase genetic homogeneity?

PubMed

Chaste, Pauline; Klei, Lambertus; Sanders, Stephan J; Hus, Vanessa; Murtha, Michael T; Lowe, Jennifer K; Willsey, A Jeremy; Moreno-De-Luca, Daniel; Yu, Timothy W; Fombonne, Eric; Geschwind, Daniel; Grice, Dorothy E; Ledbetter, David H; Mane, Shrikant M; Martin, Donna M; Morrow, Eric M; Walsh, Christopher A; Sutcliffe, James S; Lese Martin, Christa; Beaudet, Arthur L; Lord, Catherine; State, Matthew W; Cook, Edwin H; Devlin, Bernie

2015-05-01

Phenotypic heterogeneity in autism has long been conjectured to be a major hindrance to the discovery of genetic risk factors, leading to numerous attempts to stratify children based on phenotype to increase power of discovery studies. This approach, however, is based on the hypothesis that phenotypic heterogeneity closely maps to genetic variation, which has not been tested. Our study examines the impact of subphenotyping of a well-characterized autism spectrum disorder (ASD) sample on genetic homogeneity and the ability to discover common genetic variants conferring liability to ASD. Genome-wide genotypic data of 2576 families from the Simons Simplex Collection were analyzed in the overall sample and phenotypic subgroups defined on the basis of diagnosis, IQ, and symptom profiles. We conducted a family-based association study, as well as estimating heritability and evaluating allele scores for each phenotypic subgroup. Association analyses revealed no genome-wide significant association signal. Subphenotyping did not increase power substantially. Moreover, allele scores built from the most associated single nucleotide polymorphisms, based on the odds ratio in the full sample, predicted case status in subsets of the sample equally well and heritability estimates were very similar for all subgroups. In genome-wide association analysis of the Simons Simplex Collection sample, reducing phenotypic heterogeneity had at most a modest impact on genetic homogeneity. Our results are based on a relatively small sample, one with greater homogeneity than the entire population; if they apply more broadly, they imply that analysis of subphenotypes is not a productive path forward for discovering genetic risk variants in ASD. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Risk Analysis of Earth-Rock Dam Failures Based on Fuzzy Event Tree Method

PubMed Central

Fu, Xiao; Gu, Chong-Shi; Su, Huai-Zhi; Qin, Xiang-Nan

2018-01-01

Earth-rock dams make up a large proportion of the dams in China, and their failures can induce great risks. In this paper, the risks associated with earth-rock dam failure are analyzed from two aspects: the probability of a dam failure and the resulting life loss. An event tree analysis method based on fuzzy set theory is proposed to calculate the dam failure probability. The life loss associated with dam failure is summarized and refined to be suitable for Chinese dams from previous studies. The proposed method and model are applied to one reservoir dam in Jiangxi province. Both engineering and non-engineering measures are proposed to reduce the risk. The risk analysis of the dam failure has essential significance for reducing dam failure probability and improving dam risk management level. PMID:29710824

WholePathwayScope: a comprehensive pathway-based analysis tool for high-throughput data

PubMed Central

Yi, Ming; Horton, Jay D; Cohen, Jonathan C; Hobbs, Helen H; Stephens, Robert M

2006-01-01

Background Analysis of High Throughput (HTP) Data such as microarray and proteomics data has provided a powerful methodology to study patterns of gene regulation at genome scale. A major unresolved problem in the post-genomic era is to assemble the large amounts of data generated into a meaningful biological context. We have developed a comprehensive software tool, WholePathwayScope (WPS), for deriving biological insights from analysis of HTP data. Result WPS extracts gene lists with shared biological themes through color cue templates. WPS statistically evaluates global functional category enrichment of gene lists and pathway-level pattern enrichment of data. WPS incorporates well-known biological pathways from KEGG (Kyoto Encyclopedia of Genes and Genomes) and Biocarta, GO (Gene Ontology) terms as well as user-defined pathways or relevant gene clusters or groups, and explores gene-term relationships within the derived gene-term association networks (GTANs). WPS simultaneously compares multiple datasets within biological contexts either as pathways or as association networks. WPS also integrates Genetic Association Database and Partial MedGene Database for disease-association information. We have used this program to analyze and compare microarray and proteomics datasets derived from a variety of biological systems. Application examples demonstrated the capacity of WPS to significantly facilitate the analysis of HTP data for integrative discovery. Conclusion This tool represents a pathway-based platform for discovery integration to maximize analysis power. The tool is freely available at . PMID:16423281

Power of data mining methods to detect genetic associations and interactions.

PubMed

Molinaro, Annette M; Carriero, Nicholas; Bjornson, Robert; Hartge, Patricia; Rothman, Nathaniel; Chatterjee, Nilanjan

2011-01-01

Genetic association studies, thus far, have focused on the analysis of individual main effects of SNP markers. Nonetheless, there is a clear need for modeling epistasis or gene-gene interactions to better understand the biologic basis of existing associations. Tree-based methods have been widely studied as tools for building prediction models based on complex variable interactions. An understanding of the power of such methods for the discovery of genetic associations in the presence of complex interactions is of great importance. Here, we systematically evaluate the power of three leading algorithms: random forests (RF), Monte Carlo logic regression (MCLR), and multifactor dimensionality reduction (MDR). We use the algorithm-specific variable importance measures (VIMs) as statistics and employ permutation-based resampling to generate the null distribution and associated p values. The power of the three is assessed via simulation studies. Additionally, in a data analysis, we evaluate the associations between individual SNPs in pro-inflammatory and immunoregulatory genes and the risk of non-Hodgkin lymphoma. The power of RF is highest in all simulation models, that of MCLR is similar to RF in half, and that of MDR is consistently the lowest. Our study indicates that the power of RF VIMs is most reliable. However, in addition to tuning parameters, the power of RF is notably influenced by the type of variable (continuous vs. categorical) and the chosen VIM. Copyright © 2011 S. Karger AG, Basel.

CONAN: copy number variation analysis software for genome-wide association studies

PubMed Central

2010-01-01

Background Genome-wide association studies (GWAS) based on single nucleotide polymorphisms (SNPs) revolutionized our perception of the genetic regulation of complex traits and diseases. Copy number variations (CNVs) promise to shed additional light on the genetic basis of monogenic as well as complex diseases and phenotypes. Indeed, the number of detected associations between CNVs and certain phenotypes are constantly increasing. However, while several software packages support the determination of CNVs from SNP chip data, the downstream statistical inference of CNV-phenotype associations is still subject to complicated and inefficient in-house solutions, thus strongly limiting the performance of GWAS based on CNVs. Results CONAN is a freely available client-server software solution which provides an intuitive graphical user interface for categorizing, analyzing and associating CNVs with phenotypes. Moreover, CONAN assists the evaluation process by visualizing detected associations via Manhattan plots in order to enable a rapid identification of genome-wide significant CNV regions. Various file formats including the information on CNVs in population samples are supported as input data. Conclusions CONAN facilitates the performance of GWAS based on CNVs and the visual analysis of calculated results. CONAN provides a rapid, valid and straightforward software solution to identify genetic variation underlying the 'missing' heritability for complex traits that remains unexplained by recent GWAS. The freely available software can be downloaded at http://genepi-conan.i-med.ac.at. PMID:20546565

Image segmentation using association rule features.

PubMed

Rushing, John A; Ranganath, Heggere; Hinke, Thomas H; Graves, Sara J

2002-01-01

A new type of texture feature based on association rules is described. Association rules have been used in applications such as market basket analysis to capture relationships present among items in large data sets. It is shown that association rules can be adapted to capture frequently occurring local structures in images. The frequency of occurrence of these structures can be used to characterize texture. Methods for segmentation of textured images based on association rule features are described. Simulation results using images consisting of man made and natural textures show that association rule features perform well compared to other widely used texture features. Association rule features are used to detect cumulus cloud fields in GOES satellite images and are found to achieve higher accuracy than other statistical texture features for this problem.

Family-based Association Analyses of Imputed Genotypes Reveal Genome-Wide Significant Association of Alzheimer’s disease with OSBPL6, PTPRG and PDCL3

PubMed Central

Herold, Christine; Hooli, Basavaraj V.; Mullin, Kristina; Liu, Tian; Roehr, Johannes T; Mattheisen, Manuel; Parrado, Antonio R.; Bertram, Lars; Lange, Christoph; Tanzi, Rudolph E.

2015-01-01

The genetic basis of Alzheimer's disease (AD) is complex and heterogeneous. Over 200 highly penetrant pathogenic variants in the genes APP, PSEN1 and PSEN2 cause a subset of early-onset familial Alzheimer's disease (EOFAD). On the other hand, susceptibility to late-onset forms of AD (LOAD) is indisputably associated to the ε4 allele in the gene APOE, and more recently to variants in more than two-dozen additional genes identified in the large-scale genome-wide association studies (GWAS) and meta-analyses reports. Taken together however, although the heritability in AD is estimated to be as high as 80%, a large proportion of the underlying genetic factors still remain to be elucidated. In this study we performed a systematic family-based genome-wide association and meta-analysis on close to 15 million imputed variants from three large collections of AD families (~3,500 subjects from 1,070 families). Using a multivariate phenotype combining affection status and onset age, meta-analysis of the association results revealed three single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with AD risk: rs7609954 in the gene PTPRG (P-value = 3.98·10−08), rs1347297 in the gene OSBPL6 (P-value = 4.53·10−08), and rs1513625 near PDCL3 (P-value = 4.28·10−08). In addition, rs72953347 in OSBPL6 (P-value = 6.36·10−07) and two SNPs in the gene CDKAL1 showed marginally significant association with LOAD (rs10456232, P-value: 4.76·10−07; rs62400067, P-value: 3.54·10−07). In summary, family-based GWAS meta-analysis of imputed SNPs revealed novel genomic variants in (or near) PTPRG, OSBPL6, and PDCL3 that influence risk for AD with genome-wide significance. PMID:26830138

Meta-GWAS and Meta-Analysis of Exome Array Studies Do Not Reveal Genetic Determinants of Serum Hepcidin

PubMed Central

Galesloot, Tessel E.; van Dijk, Freerk; Geurts-Moespot, Anneke J.; Girelli, Domenico; Kiemeney, Lambertus A. L. M.; Sweep, Fred C. G. J.; Swertz, Morris A.; van der Meer, Peter; Camaschella, Clara; Toniolo, Daniela; Vermeulen, Sita H.; van der Harst, Pim; Swinkels, Dorine W.

2016-01-01

Serum hepcidin concentration is regulated by iron status, inflammation, erythropoiesis and numerous other factors, but underlying processes are incompletely understood. We studied the association of common and rare single nucleotide variants (SNVs) with serum hepcidin in one Italian study and two large Dutch population-based studies. We genotyped common SNVs with genome-wide association study (GWAS) arrays and subsequently performed imputation using the 1000 Genomes reference panel. Cohort-specific GWAS were performed for log-transformed serum hepcidin, adjusted for age and gender, and results were combined in a fixed-effects meta-analysis (total N 6,096). Six top SNVs (p<5x10-6) were genotyped in 3,821 additional samples, but associations were not replicated. Furthermore, we meta-analyzed cohort-specific exome array association results of rare SNVs with serum hepcidin that were available for two of the three cohorts (total N 3,226), but no exome-wide significant signal (p<1.4x10-6) was identified. Gene-based meta-analyses revealed 19 genes that showed significant association with hepcidin. Our results suggest the absence of common SNVs and rare exonic SNVs explaining a large proportion of phenotypic variation in serum hepcidin. We recommend extension of our study once additional substantial cohorts with hepcidin measurements, GWAS and/or exome array data become available in order to increase power to identify variants that explain a smaller proportion of hepcidin variation. In addition, we encourage follow-up of the potentially interesting genes that resulted from the gene-based analysis of low-frequency and rare variants. PMID:27846281

Statin use and survival in colorectal cancer: Results from a population-based cohort study and an updated systematic review and meta-analysis.

PubMed

Gray, Ronan T; Coleman, Helen G; Hughes, Carmel; Murray, Liam J; Cardwell, Chris R

2016-12-01

The aim of this study was to investigate the association between statin use and survival in a population-based colorectal cancer (CRC) cohort and perform an updated meta-analysis to quantify the magnitude of any association. A cohort of 8391 patients with newly diagnosed Dukes' A-C CRC (2009-2012) was identified from the Scottish Cancer Registry. This cohort was linked to the Prescribing Information System and the National Records of Scotland Death Records (until January 2015) to identify 1064 colorectal cancer-specific deaths. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by statin use were calculated using time dependent Cox regression models. The systematic review included relevant studies published before January 2016. Meta-analysis techniques were used to derive combined HRs for associations between statin use and cancer-specific and overall mortality. In the Scottish cohort, statin use before diagnosis (HR=0.84, 95% CI 0.75-0.94), but not after (HR=0.90, 95% CI 0.77-1.05), was associated with significantly improved cancer-specific mortality. The systematic review identified 15 relevant studies. In the meta-analysis, there was consistent (I 2 =0%,heterogeneity P=0.57) evidence of a reduction in cancer-specific mortality with statin use before diagnosis in 6 studies (n=86,622, pooled HR=0.82, 95% CI 0.79-0.86) but this association was less apparent and more heterogeneous (I 2 =67%,heterogeneity P=0.03) with statin use after diagnosis in 4 studies (n=19,152, pooled HR=0.84, 95% CI 0.68-1.04). In a Scottish CRC cohort and updated meta-analysis there was some evidence that statin use was associated with improved survival. However, these associations were weak in magnitude and, particularly for post-diagnosis use, varied markedly between studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis

PubMed Central

Chen, Juan; Wang, Zhan; Zou, Ting; Cui, Jiajia; Yin, Jiye; Zheng, Wei; Jiang, Wuzhong; Zhou, Honghao; Liu, Zhaoqian

2016-01-01

Published data showed inconsistent results about associations of extensively studied polymorphisms with platinum-based chemotherapy response. Our study aimed to provide reliable conclusions of these associations by detecting genotypes of the SNPs in a larger sample size and summarizing a comprehensive pooled analysis. 13 SNPs in 8 genes were genotyped in 1024 NSCLC patients by SequenomMassARRAY. 39 published studies and our study were included in meta-analysis. Patients with GA or GG genotypes of XRCC1 G1196 had better response than AA genotype carriers (Genotyping study: OR = 0.72, 95%CI: 0.53-0.96, P = 0.028; Meta-analysis: OR = 0.74, 95%CI: 0.62-0.89, P = 0.001). Patients carrying CT or TT genotypes of XRCC1 C580T could be more sensitive to platinum-based chemotherapy compared to patients with CC genotype (OR = 0.54, 95%CI: 0.37-0.80, P = 0.002). CC genotype of XRCC3 C18067T carriers showed more resistance to platinum-based chemotherapy when compared to those with CT or TT genotypes (OR = 0.69, 95%CI: 0.52-0.91, P = 0.009). Our study indicated that XRCC1 G1196A/C580T and XRCC3 C18067T should be paid attention for personalized platinum-based chemotherapy in NSCLC patients. PMID:27248474

Predictors of Long-Term School-Based Behavioral Outcomes in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder

PubMed Central

Reed, Margot O.; Jakubovski, Ewgeni; Johnson, Jessica A.

2017-01-01

Abstract Objective: To explore predictors of 8-year school-based behavioral outcomes in attention-deficit/hyperactivity disorder (ADHD). Methods: We examined potential baseline predictors of school-based behavioral outcomes in children who completed the 8-year follow-up in the multimodal treatment study of children with ADHD. Stepwise logistic regression and receiver operating characteristic (ROC) analysis identified baseline predictors that were associated with a higher risk of truancy, school discipline, and in-school fights. Results: Stepwise regression analysis explained between 8.1% (in-school fights) and 12.0% (school discipline) of the total variance in school-based behavioral outcomes. Logistic regression identified several baseline characteristics that were associated with school-based behavioral difficulties 8 years later, including being male (associated with truancy and school discipline), African American (school discipline, in-school fights), increased conduct disorder (CD) symptoms (truancy), decreased affection from parents (school discipline), ADHD severity (in-school fights), and study site (truancy and school discipline). ROC analyses identified the most discriminative predictors of truancy, school discipline, and in-school fights, which were Aggression and Conduct Problem Scale Total score, family income, and race, respectively. Conclusions: A modest, but nontrivial portion of school-based behavioral outcomes, was predicted by baseline childhood characteristics. Exploratory analyses identified modifiable (lack of paternal involvement, lower parental knowledge of behavioral principles, and parental use of physical punishment), somewhat modifiable (income and having comorbid CD), and nonmodifiable (African American and male) factors that were associated with school-based behavioral difficulties. Future research should confirm that the associations between earlier specific parenting behaviors and poor subsequent school-based behavioral outcomes are, indeed, causally related and independent cooccurring childhood psychopathology. Future research might target increasing paternal involvement and parental knowledge of behavioral principles and reducing use of physical punishment to improve school-based behavioral outcomes in children with ADHD. PMID:28253029

Predictors of Long-Term School-Based Behavioral Outcomes in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Reed, Margot O; Jakubovski, Ewgeni; Johnson, Jessica A; Bloch, Michael H

2017-05-01

To explore predictors of 8-year school-based behavioral outcomes in attention-deficit/hyperactivity disorder (ADHD). We examined potential baseline predictors of school-based behavioral outcomes in children who completed the 8-year follow-up in the multimodal treatment study of children with ADHD. Stepwise logistic regression and receiver operating characteristic (ROC) analysis identified baseline predictors that were associated with a higher risk of truancy, school discipline, and in-school fights. Stepwise regression analysis explained between 8.1% (in-school fights) and 12.0% (school discipline) of the total variance in school-based behavioral outcomes. Logistic regression identified several baseline characteristics that were associated with school-based behavioral difficulties 8 years later, including being male (associated with truancy and school discipline), African American (school discipline, in-school fights), increased conduct disorder (CD) symptoms (truancy), decreased affection from parents (school discipline), ADHD severity (in-school fights), and study site (truancy and school discipline). ROC analyses identified the most discriminative predictors of truancy, school discipline, and in-school fights, which were Aggression and Conduct Problem Scale Total score, family income, and race, respectively. A modest, but nontrivial portion of school-based behavioral outcomes, was predicted by baseline childhood characteristics. Exploratory analyses identified modifiable (lack of paternal involvement, lower parental knowledge of behavioral principles, and parental use of physical punishment), somewhat modifiable (income and having comorbid CD), and nonmodifiable (African American and male) factors that were associated with school-based behavioral difficulties. Future research should confirm that the associations between earlier specific parenting behaviors and poor subsequent school-based behavioral outcomes are, indeed, causally related and independent cooccurring childhood psychopathology. Future research might target increasing paternal involvement and parental knowledge of behavioral principles and reducing use of physical punishment to improve school-based behavioral outcomes in children with ADHD.

Discovery of new candidate genes for rheumatoid arthritis through integration of genetic association data with expression pathway analysis.

PubMed

Shchetynsky, Klementy; Diaz-Gallo, Lina-Marcella; Folkersen, Lasse; Hensvold, Aase Haj; Catrina, Anca Irinel; Berg, Louise; Klareskog, Lars; Padyukov, Leonid

2017-02-02

Here we integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signaling networks, relevant for rheumatoid arthritis (RA). RNA-sequencing-(RNA-seq)-based expression analysis of 377 genes from previously verified RA-associated loci was performed in blood cells from 5 newly diagnosed, non-treated patients with RA, 7 patients with treated RA and 12 healthy controls. Differentially expressed genes sharing a similar expression pattern in treated and untreated RA sub-groups were selected for pathway analysis. A set of "connector" genes derived from pathway analysis was tested for differential expression in the initial discovery cohort and validated in blood cells from 73 patients with RA and in 35 healthy controls. There were 11 qualifying genes selected for pathway analysis and these were grouped into two evidence-based functional networks, containing 29 and 27 additional connector molecules. The expression of genes, corresponding to connector molecules was then tested in the initial RNA-seq data. Differences in the expression of ERBB2, TP53 and THOP1 were similar in both treated and non-treated patients with RA and an additional nine genes were differentially expressed in at least one group of patients compared to healthy controls. The ERBB2, TP53. THOP1 expression profile was successfully replicated in RNA-seq data from peripheral blood mononuclear cells from healthy controls and non-treated patients with RA, in an independent collection of samples. Integration of RNA-seq data with findings from association studies, and consequent pathway analysis implicate new candidate genes, ERBB2, TP53 and THOP1 in the pathogenesis of RA.

Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.

PubMed

Speliotes, Elizabeth K; Yerges-Armstrong, Laura M; Wu, Jun; Hernaez, Ruben; Kim, Lauren J; Palmer, Cameron D; Gudnason, Vilmundur; Eiriksdottir, Gudny; Garcia, Melissa E; Launer, Lenore J; Nalls, Michael A; Clark, Jeanne M; Mitchell, Braxton D; Shuldiner, Alan R; Butler, Johannah L; Tomas, Marta; Hoffmann, Udo; Hwang, Shih-Jen; Massaro, Joseph M; O'Donnell, Christopher J; Sahani, Dushyant V; Salomaa, Veikko; Schadt, Eric E; Schwartz, Stephen M; Siscovick, David S; Voight, Benjamin F; Carr, J Jeffrey; Feitosa, Mary F; Harris, Tamara B; Fox, Caroline S; Smith, Albert V; Kao, W H Linda; Hirschhorn, Joel N; Borecki, Ingrid B

2011-03-01

Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.

Association between Herpesviruses and Chronic Periodontitis: A Meta-Analysis Based on Case-Control Studies.

PubMed

Zhu, Ce; Li, Fei; Wong, May Chun Mei; Feng, Xi-Ping; Lu, Hai-Xia; Xu, Wei

2015-01-01

Numerous studies have investigated the associations between herpesviruses and chronic periodontitis; however, the results remain controversial. To derive a more precise estimation, a meta-analysis on all available studies was performed to identify the association between herpesviruses and chronic periodontitis. A computerized literature search was conducted in December 2014 to identify eligible case-control studies from the PUBMED and EMBASE databases according to inclusion and exclusion criteria. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were used to assess the association between herpesviruses and risk of chronic periodontitis. A fixed or random effects model was determined based on a heterogeneity test. Sensitivity analysis was conducted to investigate stability and reliability. Publication bias was investigated using the Begg rank correlation test and Egger's funnel plot. Ten eligible studies were included to investigate the association between Epstein-Barr virus (EBV) and chronic periodontitis. The results showed that EBV has a significant association with chronic periodontitis compared with periodontally healthy group (OR = 5.74, 95% CI = 2.53-13.00, P<0.001). The association between human cytomegalovirus (HCMV) and chronic periodontitis was analyzed in 10 studies. The pooled result showed that HCMV also has a significant association with chronic periodontitis (OR = 3.59, 95% CI = 1.41-9.16, P = 0.007). Similar results were found in the sensitivity analyses. No significant publication bias was observed. Two eligible studies were included to investigate the association between herpes simplex virus (HSV) and chronic periodontitis risk. The association between HSV and chronic periodontitis was inconclusive (OR = 2.81 95% CI = 0.95-8.27, P = 0.06). Only one included study investigated the association between human herpesvirus 7 (HHV-7) and chronic periodontitis risk (OR = 1.00, 95% CI = 0.21-4.86). The findings of this meta-analysis suggest that two members of the herpesvirus family, EBV and HCMV, are significantly associated with chronic periodontitis. There is insufficient evidence to support associations between HSV, HHV-7 and chronic periodontitis.

Association between Herpesviruses and Chronic Periodontitis: A Meta-Analysis Based on Case-Control Studies

PubMed Central

Wong, May. Chun. Mei; Feng, Xi-Ping; Lu, Hai-Xia; Xu, Wei

2015-01-01

Objective Numerous studies have investigated the associations between herpesviruses and chronic periodontitis; however, the results remain controversial. To derive a more precise estimation, a meta-analysis on all available studies was performed to identify the association between herpesviruses and chronic periodontitis. Methods A computerized literature search was conducted in December 2014 to identify eligible case-control studies from the PUBMED and EMBASE databases according to inclusion and exclusion criteria. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were used to assess the association between herpesviruses and risk of chronic periodontitis. A fixed or random effects model was determined based on a heterogeneity test. Sensitivity analysis was conducted to investigate stability and reliability. Publication bias was investigated using the Begg rank correlation test and Egger's funnel plot. Results Ten eligible studies were included to investigate the association between Epstein–Barr virus (EBV) and chronic periodontitis. The results showed that EBV has a significant association with chronic periodontitis compared with periodontally healthy group (OR = 5.74, 95% CI = 2.53–13.00, P<0.001). The association between human cytomegalovirus (HCMV) and chronic periodontitis was analyzed in 10 studies. The pooled result showed that HCMV also has a significant association with chronic periodontitis (OR = 3.59, 95% CI = 1.41–9.16, P = 0.007). Similar results were found in the sensitivity analyses. No significant publication bias was observed. Two eligible studies were included to investigate the association between herpes simplex virus (HSV) and chronic periodontitis risk. The association between HSV and chronic periodontitis was inconclusive (OR = 2.81 95% CI = 0.95–8.27, P = 0.06). Only one included study investigated the association between human herpesvirus 7 (HHV-7) and chronic periodontitis risk (OR = 1.00, 95% CI = 0.21–4.86). Conclusion The findings of this meta-analysis suggest that two members of the herpesvirus family, EBV and HCMV, are significantly associated with chronic periodontitis. There is insufficient evidence to support associations between HSV, HHV-7 and chronic periodontitis. PMID:26666412

GEO Collisional Risk Assessment Based on Analysis of NASA-WISE Data and Modeling

DTIC Science & Technology

2015-10-18

GEO Collisional Risk Assessment Based on Analysis of NASA -WISE Data and Modeling Jeremy Murray Krezan1, Samantha Howard1, Phan D. Dao1, Derek...Surka2 1AFRL Space Vehicles Directorate,2Applied Technology Associates Incorporated From December 2009 through 2011 the NASA Wide-Field Infrared...of known debris. The NASA -WISE GEO belt debris population adds potentially thousands previously uncataloged objects. This paper describes

Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies

PubMed Central

Manitz, Juliane; Burger, Patricia; Amos, Christopher I.; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike

2017-01-01

The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility. PMID:28785300

Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies.

PubMed

Friedrichs, Stefanie; Manitz, Juliane; Burger, Patricia; Amos, Christopher I; Risch, Angela; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike; Hofner, Benjamin

2017-01-01

The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility.

Genome-wide copy number variation analysis identified deletions in SFMBT1 associated with fasting plasma glucose in a Han Chinese population.

PubMed

Chung, Ren-Hua; Chiu, Yen-Feng; Hung, Yi-Jen; Lee, Wen-Jane; Wu, Kwan-Dun; Chen, Hui-Ling; Lin, Ming-Wei; Chen, Yii-Der I; Quertermous, Thomas; Hsiung, Chao A

2017-08-08

Fasting glucose and fasting insulin are glycemic traits closely related to diabetes, and understanding the role of genetic factors in these traits can help reveal the etiology of type 2 diabetes. Although single nucleotide polymorphisms (SNPs) in several candidate genes have been found to be associated with fasting glucose and fasting insulin, copy number variations (CNVs), which have been reported to be associated with several complex traits, have not been reported for association with these two traits. We aimed to identify CNVs associated with fasting glucose and fasting insulin. We conducted a genome-wide CNV association analysis for fasting plasma glucose (FPG) and fasting plasma insulin (FPI) using a family-based genome-wide association study sample from a Han Chinese population in Taiwan. A family-based CNV association test was developed in this study to identify common CNVs (i.e., CNVs with frequencies ≥ 5%), and a generalized estimating equation approach was used to test the associations between the traits and counts of global rare CNVs (i.e., CNVs with frequencies <5%). We found a significant genome-wide association for common deletions with a frequency of 5.2% in the Scm-like with four mbt domains 1 (SFMBT1) gene with FPG (association p-value = 2×10 -4 and an adjusted p-value = 0.0478 for multiple testing). No significant association was observed between global rare CNVs and FPG or FPI. The deletions in 20 individuals with DNA samples available were successfully validated using PCR-based amplification. The association of the deletions in SFMBT1 with FPG was further evaluated using an independent population-based replication sample obtained from the Taiwan Biobank. An association p-value of 0.065, which was close to the significance level of 0.05, for FPG was obtained by testing 9 individuals with CNVs in the SFMBT1 gene region and 11,692 individuals with normal copies in the replication cohort. Previous studies have found that SNPs in SFMBT1 are associated with blood pressure and serum urate concentration, suggesting that SFMBT1 may have functional implications in some metabolic-related traits.

Constructional and Conceptual Composition

ERIC Educational Resources Information Center

Dodge, Ellen Kirsten

2010-01-01

Goldberg's (1995) recognition that, in addition to various word-level constructions, sentences also instantiate meaningful argument structure constructions enables a non-polysemy-based analysis of various verb 'alternations' (Levin 1993). In such an analysis, meaning variations associated with the use of the same verb in different argument…

Systematic Analysis of Icotinib Treatment for Patients with Non-Small Cell Lung Cancer.

PubMed

Shi, Bing; Zhang, Xiu-Bing; Xu, Jian; Huang, Xin-En

2015-01-01

This analysis was conducted to evaluate the efficacy and safety of icotinib based regimens in treating patients with non-small cell lung cancer (NSCLC). Clinical studies evaluating the efficacy and safety of icotinib-based regimens with regard to response and safety for patients with NSCLC were identified using a predefined search strategy. Pooled response rates of treatment were calculated. With icotinib-based regimens, 7 clinical studies which including 5,985 Chinese patients with NSCLC were considered eligible for inclusion. The pooled analysis suggested that, in all patients, the positive reponse rate was 30.1% (1,803/5,985) with icotinib-based regimens. Mild skin itching, rashes and diarrhea were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment-related death occurred in patients treated with icotinib-based regimens. This evidence based analysis suggests that icotinib based regimens are associated with mild response rate and acceptable toxicity for treating Chinese patients with NSCLC.

Comparative analysis reveals that polyploidy does not decelerate diversification in fish.

PubMed

Zhan, S H; Glick, L; Tsigenopoulos, C S; Otto, S P; Mayrose, I

2014-02-01

While the proliferation of the species-rich teleost fish has been ascribed to an ancient genome duplication event at the base of this group, the broader impact of polyploidy on fish evolution and diversification remains poorly understood. Here, we investigate the association between polyploidy and diversification in several fish lineages: the sturgeons (Acipenseridae: Acipenseriformes), the botiid loaches (Botiidae: Cypriniformes), Cyprininae fishes (Cyprinidae: Cypriniformes) and the salmonids (Salmonidae: Salmoniformes). Using likelihood-based evolutionary methodologies, we co-estimate speciation and extinction rates associated with polyploid vs. diploid fish lineages. Family-level analysis of Acipenseridae and Botiidae revealed no significant difference in diversification rates between polyploid and diploid relatives, while analysis of the subfamily Cyprininae revealed higher polyploid diversification. Additionally, order-level analysis of the polyploid Salmoniformes and its diploid sister clade, the Esociformes, did not support a significantly different net diversification rate between the two groups. Taken together, our results suggest that polyploidy is generally not associated with decreased diversification in fish - a pattern that stands in contrast to that previously observed in plants. While there are notable differences in the time frame examined in the two studies, our results suggest that polyploidy is associated with different diversification patterns in these two major branches of the eukaryote tree of life. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Mediation Analysis Demonstrates That Trans-eQTLs Are Often Explained by Cis-Mediation: A Genome-Wide Analysis among 1,800 South Asians

PubMed Central

Pierce, Brandon L.; Tong, Lin; Chen, Lin S.; Rahaman, Ronald; Argos, Maria; Jasmine, Farzana; Roy, Shantanu; Paul-Brutus, Rachelle; Westra, Harm-Jan; Franke, Lude; Esko, Tonu; Zaman, Rakibuz; Islam, Tariqul; Rahman, Mahfuzar; Baron, John A.; Kibriya, Muhammad G.; Ahsan, Habibul

2014-01-01

A large fraction of human genes are regulated by genetic variation near the transcribed sequence (cis-eQTL, expression quantitative trait locus), and many cis-eQTLs have implications for human disease. Less is known regarding the effects of genetic variation on expression of distant genes (trans-eQTLs) and their biological mechanisms. In this work, we use genome-wide data on SNPs and array-based expression measures from mononuclear cells obtained from a population-based cohort of 1,799 Bangladeshi individuals to characterize cis- and trans-eQTLs and determine if observed trans-eQTL associations are mediated by expression of transcripts in cis with the SNPs showing trans-association, using Sobel tests of mediation. We observed 434 independent trans-eQTL associations at a false-discovery rate of 0.05, and 189 of these trans-eQTLs were also cis-eQTLs (enrichment P<0.0001). Among these 189 trans-eQTL associations, 39 were significantly attenuated after adjusting for a cis-mediator based on Sobel P<10-5. We attempted to replicate 21 of these mediation signals in two European cohorts, and while only 7 trans-eQTL associations were present in one or both cohorts, 6 showed evidence of cis-mediation. Analyses of simulated data show that complete mediation will be observed as partial mediation in the presence of mediator measurement error or imperfect LD between measured and causal variants. Our data demonstrates that trans-associations can become significantly stronger or switch directions after adjusting for a potential mediator. Using simulated data, we demonstrate that this phenomenon is expected in the presence of strong cis-trans confounding and when the measured cis-transcript is correlated with the true (unmeasured) mediator. In conclusion, by applying mediation analysis to eQTL data, we show that a substantial fraction of observed trans-eQTL associations can be explained by cis-mediation. Future studies should focus on understanding the mechanisms underlying widespread cis-mediation and their relevance to disease biology, as well as using mediation analysis to improve eQTL discovery. PMID:25474530

Metabolic Disturbances in Adult-Onset Still's Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis.

PubMed

Chen, Der-Yuan; Chen, Yi-Ming; Chien, Han-Ju; Lin, Chi-Chen; Hsieh, Chia-Wei; Chen, Hsin-Hua; Hung, Wei-Ting; Lai, Chien-Chen

2016-01-01

Liquid chromatography/mass spectrometry (LC/MS)-based comprehensive analysis of metabolic profiles with metabolomics approach has potential diagnostic and predictive implications. However, no metabolomics data have been reported in adult-onset Still's disease (AOSD). This study investigated the metabolomic profiles in AOSD patients and examined their association with clinical characteristics and disease outcome. Serum metabolite profiles were determined on 32 AOSD patients and 30 healthy controls (HC) using ultra-performance liquid chromatography (UPLC)/MS analysis, and the differentially expressed metabolites were quantified using multiple reactions monitoring (MRM)/MS analysis in 44 patients and 42 HC. Pure standards were utilized to confirm the presence of the differentially expressed metabolites. Eighteen differentially expressed metabolites were identified in AOSD patents using LC/MS-based analysis, of which 13 metabolites were validated by MRM/MS analysis. Among them, serum levels of lysoPC(18:2), urocanic acid and indole were significantly lower, and L-phenylalanine levels were significantly higher in AOSD patients compared with HC. Moreover, serum levels of lysoPC(18:2), PhePhe, uridine, taurine, L-threonine, and (R)-3-Hydroxy-hexadecanoic acid were significantly correlated with disease activity scores (all p<0.05) in AOSD patients. A different clustering of metabolites was associated with a different disease outcome, with significantly lower levels of isovalerylsarcosine observed in patients with chronic articular pattern (median, 77.0AU/ml) compared with monocyclic (341.5AU/ml, p<0.01) or polycyclic systemic pattern (168.0AU/ml, p<0.05). Thirteen differentially expressed metabolites identified and validated in AOSD patients were shown to be involved in five metabolic pathways. Significant associations of metabolic profiles with disease activity and outcome of AOSD suggest their involvement in AOSD pathogenesis.

Two time-series analyses of the impact of antibiotic consumption and alcohol-based hand disinfection on the incidences of nosocomial methicillin-resistant Staphylococcus aureus infection and Clostridium difficile infection.

PubMed

Kaier, Klaus; Hagist, Christian; Frank, Uwe; Conrad, Andreas; Meyer, Elisabeth

2009-04-01

To determine the impact of antibiotic consumption and alcohol-based hand disinfection on the incidences of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection and Clostridium difficile infection (CDI). Two multivariate time-series analyses were performed that used as dependent variables the monthly incidences of nosocomial MRSA infection and CDI at the Freiburg University Medical Center during the period January 2003 through October 2007. The volume of alcohol-based hand rub solution used per month was quantified in liters per 1,000 patient-days. Antibiotic consumption was calculated in terms of the number of defined daily doses per 1,000 patient-days per month. The use of alcohol-based hand rub was found to have a significant impact on the incidence of nosocomial MRSA infection (P< .001). The multivariate analysis (R2=0.66) showed that a higher volume of use of alcohol-based hand rub was associated with a lower incidence of nosocomial MRSA infection. Conversely, a higher level of consumption of selected antimicrobial agents was associated with a higher incidence of nosocomial MRSA infection. This analysis showed this relationship was the same for the use of second-generation cephalosporins (P= .023), third-generation cephalosporins (P= .05), fluoroquinolones (P= .01), and lincosamides (P= .05). The multivariate analysis (R2=0.55) showed that a higher level of consumption of third-generation cephalosporins (P= .008), fluoroquinolones (P= .084), and/or macrolides (P= .007) was associated with a higher incidence of CDI. A correlation with use of alcohol-based hand rub was not detected. In 2 multivariate time-series analyses, we were able to show the impact of hand hygiene and antibiotic use on the incidence of nosocomial MRSA infection, but we found no association between hand hygiene and incidence of CDI.

Thromboembolic events in cancer patients on active treatment with cisplatin-based chemotherapy: another look!

PubMed

Abdel-Razeq, Hikmat; Mansour, Asem; Abdulelah, Hazem; Al-Shwayat, Anas; Makoseh, Mohammad; Ibrahim, Mohammad; Abunasser, Mahmoud; Rimawi, Dalia; Al-Rabaiah, Abeer; Alfar, Rozan; Abufara, Alaa'; Ibrahim, Alaa; Bawaliz, Anas; Ismael, Yousef

2018-01-01

The risk of thromboembolic events is higher among cancer patients, especially in patients undergoing chemotherapy. Cisplatin-based regimens claim to be associated with a very high thromboembolic rate. In this study, we report on our own experience with thrombosis among patients on active cisplatin-based chemotherapy. Medical records and hospital databases were searched for all the patients treated with any cisplatin-based regimen for any kind of cancer. Thrombosis was considered cisplatin-related if diagnosed any time after the first dose and up to 4 weeks after the last. The Khorana risk assessment model was performed in all cases. A total of 1677 patients (65.5% males, median age: 50 years) treated with cisplatin-based regimens were identified. Head and neck (22.9%), lung (22.2%), lymphoma and gastric (11.4% each) were the most common primary tumors. Thromboembolic events were reported in 110 (6.6%); the highest was in patients with gastric cancer (20.9%) and the lowest in patients with head and neck cancers (2.3%) and lymphoma (1.6%). Thrombosis included deep vein thrombosis (DVT) in 69 (62.7%), pulmonary embolism (PE) in 18 (16.9%) and arterial thrombosis in 17 (15.6%). A majority (51.1%) of the patients had stage IV disease and only 16% had stage I or II.In a multivariate analysis, significantly higher rates of thrombosis were associated with gastric as the primary tumor, advanced-stage disease, female sex but not age, and the Khorana risk score or type of cisplatin regimen. While the presence of CVC was significantly associated with the risk of thrombosis ( p  < 0.0001) in the univariate analysis, and such significance was lost in the multivariate analysis (odds ratio, 1.098; 95%CI, 0.603-1.999, p  = 0.7599). Thromboembolic events in cancer patients on active cisplatin-based chemotherapy were commonly encountered. Gastric cancer, regardless of other clinical variables, was associated with the highest risk.

The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis.

PubMed

LoParo, D; Waldman, I D

2015-05-01

The oxytocin receptor gene (OXTR) has been studied as a risk factor for autism spectrum disorder (ASD) owing to converging evidence from multiple levels of analysis that oxytocin (OXT) has an important role in the regulation of affiliative behavior and social bonding in both nonhuman mammals and humans. Inconsistency in the effect sizes of the OXTR variants included in association studies render it unclear whether OXTR is truly associated with ASD, and, if so, which OXTR single-nucleotide polymorphisms (SNPs) are associated. Thus, a meta-analytic review of extant studies is needed to determine whether OXTR shows association with ASD, and to elucidate which specific SNPs have a significant effect on ASD. The current meta-analysis of 16 OXTR SNPs included 3941 individuals with ASD from 11 independent samples, although analyses of each individual SNP included a subset of this total. We found significant associations between ASD and the SNPs rs7632287, rs237887, rs2268491 and rs2254298. OXTR was also significantly associated with ASD in a gene-based test. The current meta-analysis is the largest and most comprehensive investigation of the association of OXTR with ASD and the findings suggest directions for future studies of the etiology of ASD.

Home practice in Mindfulness-Based Cognitive Therapy and Mindfulness-Based Stress Reduction: A systematic review and meta-analysis of participants' mindfulness practice and its association with outcomes.

PubMed

Parsons, Christine E; Crane, Catherine; Parsons, Liam J; Fjorback, Lone Overby; Kuyken, Willem

2017-08-01

Mindfulness-Based Cognitive Therapy (MBCT) and Mindfulness-Based Stress Reduction (MBSR) emphasize the importance of mindfulness practice at home as an integral part of the program. However, the extent to which participants complete their assigned practice is not yet clear, nor is it clear whether this practice is associated with positive outcomes. For this systematic review and meta-analysis, searches were performed using Scopus and PubMed for studies published through to the end of 2015, reporting on formal home practice of mindfulness by MBSR or MBCT participants. Across 43 studies (N = 1427), the pooled estimate for participants' home practice was 64% of the assigned amount, equating to about 30 minutes per day, six days per week [95% CI 60-69%]. There was substantial heterogeneity associated with this estimate. Across 28 studies (N = 898), there was a small but significant association between participants' self-reported home practice and intervention outcomes (r = 0·26, 95% CI 0·19,-0·34). MBSR and MBCT participants report completing substantial formal mindfulness practice at home over the eight-week intervention, albeit less than assigned amounts. There is a small but significant association between the extent of formal practice and positive intervention outcomes for a wide range of participants. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

A Family-Based Association Analysis and Meta-Analysis of the Reading Disabilities Candidate Gene DYX1C1

PubMed Central

Tran, C.; Gagnon, F.; Wigg, K.G.; Feng, Y.; Gomez, L.; Cate-Carter, T.D.; Kerr, E.N.; Field, L.L.; Kaplan, B.J.; Lovett, M.W.; Barr, C.L.

2017-01-01

Reading disabilities (RD) have a significant genetic basis and have shown linkage to multiple regions including chromosome 15q. Dyslexia susceptibility 1 candidate gene 1 (DYX1C1) on chromosome 15q21 was originally proposed as a candidate gene with two potentially functional polymorphisms at the −3G/A and 1249G/T positions showing association with RD. However, subsequent studies have yielded mixed results. We performed a literature review and meta-analysis of the −3G/A and 1249G/T polymorphisms, including new unpublished data from two family-based samples. Ten markers in DYX1C1 were genotyped in the two independently ascertained samples. Single marker and −3G/A:1249G/T haplotype analyses were performed for RD in both samples, and quantitative trait analyses using standardized reading-related measures was performed in one of the samples. For the meta-analysis, we used a random-effects model to summarize studies that tested for association between −3G/A or 1249G/T and RD. No significant association was found between the DYX1C1 SNPs and RD or any of the reading-related measures tested after correction for the number of tests performed. The previously reported risk haplotype (−3A:1249T) was not biased in transmission. A total of 9 and 10 study samples were included in the meta-analysis of the −3G/A and 1249G/T polymorphisms, respectively. Neither polymorphism reached statistical significance, but the heterogeneity for the 1249G/T polymorphism was high. The results of this study do not provide evidence for association between the putatively functional SNPs −3G/A and 1249G/T and RD. PMID:23341075

Body mass index and risk of BPH: a meta-analysis.

PubMed

Wang, S; Mao, Q; Lin, Y; Wu, J; Wang, X; Zheng, X; Xie, L

2012-09-01

Epidemiological studies have reported conflicting results relating obesity to BPH. A meta-analysis of cohort and case-control studies was conducted to pool the risk estimates of the association between obesity and BPH. Eligible studies were retrieved by both computer searches and review of references. We analyzed abstracted data with random effects models to obtain the summary risk estimates. Dose-response meta-analysis was performed for studies reporting categorical risk estimates for a series of exposure levels. A total of 19 studies met the inclusion criteria of the meta-analysis. Positive association with body mass index (BMI) was observed in BPH and lower urinary tract symptoms (LUTS) combined group (odds ratio=1.27, 95% confidence intervals 1.05-1.53). In subgroup analysis, BMI exhibited a positive dose-response relationship with BPH/LUTS in population-based case-control studies and a marginal positive association was observed between risk of BPH and increased BMI. However, no association between BPH/LUTS and BMI was observed in other subgroups stratified by study design, geographical region or primary outcome. The overall current literatures suggested that BMI was associated with increased risk of BPH. Further efforts should be made to confirm these findings and clarify the underlying biological mechanisms.

Strain-based HLA association analysis identified HLA-DRB1*09:01 associated with modern strain tuberculosis.

PubMed

Toyo-Oka, L; Mahasirimongkol, S; Yanai, H; Mushiroda, T; Wattanapokayakit, S; Wichukchinda, N; Yamada, N; Smittipat, N; Juthayothin, T; Palittapongarnpim, P; Nedsuwan, S; Kantipong, P; Takahashi, A; Kubo, M; Sawanpanyalert, P; Tokunaga, K

2017-09-01

Tuberculosis (TB) occurs as a result of complex interactions between the host immune system and pathogen virulence factors. Human leukocyte antigen (HLA) class II molecules play an important role in the host immune system. However, no study has assessed the association between HLA class II genes and susceptibility to TB caused by specific strains. This study investigated the possible association of HLA class II genes with TB caused by modern and ancient Mycobacterium tuberculosis (MTB). The study included 682 patients with TB and 836 control subjects who were typed for HLA-DRB1 and HLA-DQB1 alleles. MTB strains were classified using a large sequence polymorphism typing method. Association analysis was performed using common HLA alleles and haplotypes in different MTB strains. HLA association analysis of patients infected with modern MTB strains showed significant association for HLA-DRB1*09:01 (odds ratio [OR] = 1.82; P-value = 9.88 × 10 -4 ) and HLA-DQB1*03:03 alleles (OR = 1.76; P-value = 1.31 × 10 -3 ) with susceptibility to TB. Haplotype analysis confirmed that these alleles were in strong linkage disequilibrium and did not exert an interactive effect. Thus, the results of this study showed an association between HLA class II genes and susceptibility to TB caused by modern MTB strains, suggesting the importance of strain-specific analysis to determine susceptibility genes associated with TB. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Correlates of HIV infection among street-based and venue-based sex workers in Vietnam.

PubMed

Le, Thuy Tc; Nguyen, Quoc C; Tran, Ha Tt; Schwandt, Michael; Lim, Hyun J

2016-10-01

Commercial sex work is one of the driving forces of the HIV epidemic across the world. In Vietnam, although female sex workers (FSWs) carry a disproportionate burden of HIV, little is known about the risk profile and associated factors for HIV infection among this population. There is a need for large-scale research to obtain reliable and representative estimates of the measures of association. This study involved secondary data analysis of the 'HIV/STI Integrated Biological and Behavioral Surveillance' study in Vietnam in 2009-2010 to examine the correlates of HIV among FSWs. Data collected from 5298 FSWs, including 2530 street-based sex workers and 2768 venue-based sex workers from 10 provinces in Vietnam, were analyzed using descriptive statistics and bivariate and multivariate logistic regression analyses. HIV prevalence among the overall FSW population was 8.6% (n = 453). However, when stratified by FSW subpopulations, HIV prevalence was 10.6% (n = 267) for street-based sex workers and 6.7% (n = 186) for venue-based sex workers. Factors independently associated with HIV infection in the multivariate analysis, regardless of sex work types, were injecting drug use, high self-perceived HIV risk, and age ≥ 25 years. Additional factors independently associated with HIV risk within each FSW subpopulation included having ever been married among street-based sex workers and inconsistent condom use with clients and having sex partners who injected drugs among venue-based sex workers. Apart from strategies addressing modifiable risk behaviours among all FSWs, targeted strategies to address specific risk behaviours within each FSW subpopulation should be adopted. © The Author(s) 2016.

Graph-Theoretic Properties of Networks Based on Word Association Norms: Implications for Models of Lexical Semantic Memory

ERIC Educational Resources Information Center

Gruenenfelder, Thomas M.; Recchia, Gabriel; Rubin, Tim; Jones, Michael N.

2016-01-01

We compared the ability of three different contextual models of lexical semantic memory (BEAGLE, Latent Semantic Analysis, and the Topic model) and of a simple associative model (POC) to predict the properties of semantic networks derived from word association norms. None of the semantic models were able to accurately predict all of the network…

HYDROLOGIC MODEL UNCERTAINTY ASSOCIATED WITH SIMULATING FUTURE LAND-COVER/USE SCENARIOS: A RETROSPECTIVE ANALYSIS

EPA Science Inventory

GIS-based hydrologic modeling offers a convenient means of assessing the impacts associated with land-cover/use change for environmental planning efforts. Alternative future scenarios can be used as input to hydrologic models and compared with existing conditions to evaluate pot...

Sensory Processing Subtypes in Autism: Association with Adaptive Behavior

ERIC Educational Resources Information Center

Lane, Alison E.; Young, Robyn L.; Baker, Amy E. Z.; Angley, Manya T.

2010-01-01

Children with autism are frequently observed to experience difficulties in sensory processing. This study examined specific patterns of sensory processing in 54 children with autistic disorder and their association with adaptive behavior. Model-based cluster analysis revealed three distinct sensory processing subtypes in autism. These subtypes…

Whole-genome association analysis of pork meat pH revealed three significant regions and several potential genes in Finnish Yorkshire pigs.

PubMed

Verardo, Lucas L; Sevón-Aimonen, Marja-Liisa; Serenius, Timo; Hietakangas, Ville; Uimari, Pekka

2017-02-13

One of the most commonly used quality measurements of pork is pH measured 24 h after slaughter. The most probable mode of inheritance for this trait is oligogenic with several known major genes, such as PRKAG3. In this study, we used whole-genome SNP genotypes of over 700 AI boars; after a quality check, 42,385 SNPs remained for association analysis. All the boars were purebred Finnish Yorkshire. To account for relatedness of the animals, a pedigree-based relationship matrix was used in a mixed linear model to test the effect of SNPs on pH measured from loin. A bioinformatics analysis was performed to identify the most promising genes in the significant regions related to meat quality. Genome-wide association study (GWAS) revealed three significant chromosomal regions: one on chromosome 3 (39.9 Mb-40.1 Mb) and two on chromosome 15 (58.5 Mb-60.5 Mb and 132 Mb-135 Mb including PRKAG3). A conditional analysis with a significant SNP in the PRKAG3 region, MARC0083357, as a covariate in the model retained the significant SNPs on chromosome 3. Even though linkage disequilibrium was relatively high over a long distance between MARC0083357 and other significant SNPs on chromosome 15, some SNPs retained their significance in the conditional analysis, even in the vicinity of PRKAG3. The significant regions harbored several genes, including two genes involved in cyclic AMP (cAMP) signaling: ADCY9 and CREBBP. Based on functional and transcription factor-gene networks, the most promising candidate genes for meat pH are ADCY9, CREBBP, TRAP1, NRG1, PRKAG3, VIL1, TNS1, and IGFBP5, and the key transcription factors related to these genes are HNF4A, PPARG, and Nkx2-5. Based on SNP association, pathway, and transcription factor analysis, we were able to identify several genes with potential to control muscle cell homeostasis and meat quality. The associated SNPs can be used in selection for better pork. We also showed that post-GWAS analysis reveals important information about the genes' potential role on meat quality. The gained information can be used in later functional studies.

Genome-wide association study of rust traits in orchardgrass using SLAF-seq technology.

PubMed

Zeng, Bing; Yan, Haidong; Liu, Xinchun; Zang, Wenjing; Zhang, Ailing; Zhou, Sifan; Huang, Linkai; Liu, Jinping

2017-01-01

While orchardgrass ( Dactylis glomerata L.) is a well-known perennial forage species, rust diseases cause serious reductions in the yield and quality of orchardgrass; however, genetic mechanisms of rust resistance are not well understood in orchardgrass. In this study, a genome-wide association study (GWAS) was performed using specific-locus amplified fragment sequencing (SLAF-seq) technology in orchardgrass. A total of 2,334,889 SLAF tags were generated to produce 2,309,777 SNPs. ADMIXTURE analysis revealed unstructured subpopulations for 33 accessions, indicating that this orchardgrass population could be used for association analysis. Linkage disequilibrium (LD) analysis revealed an average r 2 of 0.4 across all SNP pairs, indicating a high extent of LD in these samples. Through GWAS, a total of 4,604 SNPs were found to be significantly ( P  < 0.01) associated with the rust trait. The bulk analysis discovered a number of 5,211 SNPs related to rust trait. Two candidate genes, including cytochrome P450, and prolamin were implicated in disease resistance through prediction of functional genes surrounding each high-quality SNP ( P  < 0.01) associated with rust traits based on GWAS analysis and bulk analysis. The large number of SNPs associated with rust traits and these two candidate genes may provide the basis for further research on rust resistance mechanisms and marker-assisted selection (MAS) for rust-resistant lineages.

The association between uterine leiomyoma and placenta abruption: A meta-analysis.

PubMed

Jenabi, Ensiyeh; Ebrahimzadeh Zagami, Samira

2017-11-01

Some epidemiological studies have found that uterine leiomyoma can increase the risk of placenta abruption. To date, the meta-analysis has not been performed for assessing the relationship between uterine leiomyoma and placenta abruption. This meta-analysis was conducted to estimate the association between uterine leiomyoma and the risk of placenta abruption. A literature search was conducted out in major databases PubMed, Web of Science, and Scopus from the earliest possible year to October 2016. The heterogeneity across studies was explored by Q-test and I 2 statistic. The publication bias was assessed by Begg's and Egger's tests. The results were showed using odds ratio (OR) estimate with its 95% confidence intervals (CI) using a random-effects model. The literature search included 953 articles until October 2016 with 232,024 participants. Based on OR estimates obtained from case-control and cohort studies, there was significant association between uterine leiomyoma and placenta abruption (2.63; 95% CI: 1.38, 3.88). We showed based on reports in observational studies that uterine leiomyoma is a risk factor for placenta abruption.

Phosphorylation of ETS-1 is a critical event in DNA polymerase iota-induced invasion and metastasis of esophageal squamous cell carcinoma.

PubMed

He, Chao; Wu, Shuhua; Gao, Aidi; Su, Ye; Min, Han; Shang, Zeng-Fu; Wu, Jinchang; Yang, Li; Ding, Wei-Qun; Zhou, Jundong

2017-12-01

An aberrantly elevated expression of DNA polymerase ι (Pol ι) is significantly associated with poor prognosis of patients with esophageal squamous cell carcinoma (ESCC), yet the mechanisms behind this phenomenon remain obscure. Based on the RNA-Seq transcriptome and real-time PCR analysis, we identified ETS-1 as a candidate gene involved in Pol ι-mediated progression of ESCC. Wound-healing and transwell assay indicated that downregulation of ETS-1 attenuates Pol ι-mediated invasiveness of ESCC. Signaling pathway analysis showed that Pol ι enhances ETS-1 phosphorylation at threonine-38 through the Erk signaling pathway in ESCC cells. Kaplan-Meier analysis, based on 93 clinical tissue samples, revealed that ETS-1 phosphorylation at threonine-38 is associated with poor prognosis of ESCC patients. The present study thus demonstrates that phosphorylation of ETS-1 is a critical event in the Pol ι-induced invasion and metastasis of ESCC. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Long-Term Functional Outcomes and Correlation with Regional Brain Connectivity by MRI Diffusion Tractography Metrics in a Near-Term Rabbit Model of Intrauterine Growth Restriction

PubMed Central

Illa, Miriam; Eixarch, Elisenda; Batalle, Dafnis; Arbat-Plana, Ariadna; Muñoz-Moreno, Emma; Figueras, Francesc; Gratacos, Eduard

2013-01-01

Background Intrauterine growth restriction (IUGR) affects 5–10% of all newborns and is associated with increased risk of memory, attention and anxiety problems in late childhood and adolescence. The neurostructural correlates of long-term abnormal neurodevelopment associated with IUGR are unknown. Thus, the aim of this study was to provide a comprehensive description of the long-term functional and neurostructural correlates of abnormal neurodevelopment associated with IUGR in a near-term rabbit model (delivered at 30 days of gestation) and evaluate the development of quantitative imaging biomarkers of abnormal neurodevelopment based on diffusion magnetic resonance imaging (MRI) parameters and connectivity. Methodology At +70 postnatal days, 10 cases and 11 controls were functionally evaluated with the Open Field Behavioral Test which evaluates anxiety and attention and the Object Recognition Task that evaluates short-term memory and attention. Subsequently, brains were collected, fixed and a high resolution MRI was performed. Differences in diffusion parameters were analyzed by means of voxel-based and connectivity analysis measuring the number of fibers reconstructed within anxiety, attention and short-term memory networks over the total fibers. Principal Findings The results of the neurobehavioral and cognitive assessment showed a significant higher degree of anxiety, attention and memory problems in cases compared to controls in most of the variables explored. Voxel-based analysis (VBA) revealed significant differences between groups in multiple brain regions mainly in grey matter structures, whereas connectivity analysis demonstrated lower ratios of fibers within the networks in cases, reaching the statistical significance only in the left hemisphere for both networks. Finally, VBA and connectivity results were also correlated with functional outcome. Conclusions The rabbit model used reproduced long-term functional impairments and their neurostructural correlates of abnormal neurodevelopment associated with IUGR. The description of the pattern of microstructural changes underlying functional defects may help to develop biomarkers based in diffusion MRI and connectivity analysis. PMID:24143189

Long-term functional outcomes and correlation with regional brain connectivity by MRI diffusion tractography metrics in a near-term rabbit model of intrauterine growth restriction.

PubMed

Illa, Miriam; Eixarch, Elisenda; Batalle, Dafnis; Arbat-Plana, Ariadna; Muñoz-Moreno, Emma; Figueras, Francesc; Gratacos, Eduard

2013-01-01

Intrauterine growth restriction (IUGR) affects 5-10% of all newborns and is associated with increased risk of memory, attention and anxiety problems in late childhood and adolescence. The neurostructural correlates of long-term abnormal neurodevelopment associated with IUGR are unknown. Thus, the aim of this study was to provide a comprehensive description of the long-term functional and neurostructural correlates of abnormal neurodevelopment associated with IUGR in a near-term rabbit model (delivered at 30 days of gestation) and evaluate the development of quantitative imaging biomarkers of abnormal neurodevelopment based on diffusion magnetic resonance imaging (MRI) parameters and connectivity. At +70 postnatal days, 10 cases and 11 controls were functionally evaluated with the Open Field Behavioral Test which evaluates anxiety and attention and the Object Recognition Task that evaluates short-term memory and attention. Subsequently, brains were collected, fixed and a high resolution MRI was performed. Differences in diffusion parameters were analyzed by means of voxel-based and connectivity analysis measuring the number of fibers reconstructed within anxiety, attention and short-term memory networks over the total fibers. The results of the neurobehavioral and cognitive assessment showed a significant higher degree of anxiety, attention and memory problems in cases compared to controls in most of the variables explored. Voxel-based analysis (VBA) revealed significant differences between groups in multiple brain regions mainly in grey matter structures, whereas connectivity analysis demonstrated lower ratios of fibers within the networks in cases, reaching the statistical significance only in the left hemisphere for both networks. Finally, VBA and connectivity results were also correlated with functional outcome. The rabbit model used reproduced long-term functional impairments and their neurostructural correlates of abnormal neurodevelopment associated with IUGR. The description of the pattern of microstructural changes underlying functional defects may help to develop biomarkers based in diffusion MRI and connectivity analysis.

Linkage and related analyses of Barrett's esophagus and its associated adenocarcinomas.

PubMed

Sun, Xiangqing; Elston, Robert; Falk, Gary W; Grady, William M; Faulx, Ashley; Mittal, Sumeet K; Canto, Marcia I; Shaheen, Nicholas J; Wang, Jean S; Iyer, Prasad G; Abrams, Julian A; Willis, Joseph E; Guda, Kishore; Markowitz, Sanford; Barnholtz-Sloan, Jill S; Chandar, Apoorva; Brock, Wendy; Chak, Amitabh

2016-07-01

Familial aggregation and segregation analysis studies have provided evidence of a genetic basis for esophageal adenocarcinoma (EAC) and its premalignant precursor, Barrett's esophagus (BE). We aim to demonstrate the utility of linkage analysis to identify the genomic regions that might contain the genetic variants that predispose individuals to this complex trait (BE and EAC). We genotyped 144 individuals in 42 multiplex pedigrees chosen from 1000 singly ascertained BE/EAC pedigrees, and performed both model-based and model-free linkage analyses, using S.A.G.E. and other software. Segregation models were fitted, from the data on both the 42 pedigrees and the 1000 pedigrees, to determine parameters for performing model-based linkage analysis. Model-based and model-free linkage analyses were conducted in two sets of pedigrees: the 42 pedigrees and a subset of 18 pedigrees with female affected members that are expected to be more genetically homogeneous. Genome-wide associations were also tested in these families. Linkage analyses on the 42 pedigrees identified several regions consistently suggestive of linkage by different linkage analysis methods on chromosomes 2q31, 12q23, and 4p14. A linkage on 15q26 is the only consistent linkage region identified in the 18 female-affected pedigrees, in which the linkage signal is higher than in the 42 pedigrees. Other tentative linkage signals are also reported. Our linkage study of BE/EAC pedigrees identified linkage regions on chromosomes 2, 4, 12, and 15, with some reported associations located within our linkage peaks. Our linkage results can help prioritize association tests to delineate the genetic determinants underlying susceptibility to BE and EAC.

The Role of Sexual Orientation in School-Based Victimization: A Meta-Analysis

ERIC Educational Resources Information Center

Toomey, Russell B.; Russell, Stephen T.

2016-01-01

School-based victimization is associated with poorer developmental, academic, and health outcomes. This meta-analytic review compared the mean levels of school-based victimization experienced by sexual minority youth to those of heterosexual youth, and examined moderators of this difference. Results from 18 independent studies (N = 56,752…

Long working hours and alcohol use: systematic review and meta-analysis of published studies and unpublished individual participant data

PubMed Central

Jokela, Markus; Nyberg, Solja T; Madsen, Ida E H; Lallukka, Tea; Ahola, Kirsi; Alfredsson, Lars; Batty, G David; Bjorner, Jakob B; Borritz, Marianne; Burr, Hermann; Casini, Annalisa; Clays, Els; De Bacquer, Dirk; Dragano, Nico; Erbel, Raimund; Ferrie, Jane E; Fransson, Eleonor I; Hamer, Mark; Heikkilä, Katriina; Jöckel, Karl-Heinz; Kittel, France; Knutsson, Anders; Koskenvuo, Markku; Ladwig, Karl-Heinz; Lunau, Thorsten; Nielsen, Martin L; Nordin, Maria; Oksanen, Tuula; Pejtersen, Jan H; Pentti, Jaana; Rugulies, Reiner; Salo, Paula; Schupp, Jürgen; Siegrist, Johannes; Singh-Manoux, Archana; Steptoe, Andrew; Suominen, Sakari B; Theorell, Töres; Vahtera, Jussi; Wagner, Gert G; Westerholm, Peter J M; Westerlund, Hugo; Kivimäki, Mika

2015-01-01

Objective To quantify the association between long working hours and alcohol use. Design Systematic review and meta-analysis of published studies and unpublished individual participant data. Data sources A systematic search of PubMed and Embase databases in April 2014 for published studies, supplemented with manual searches. Unpublished individual participant data were obtained from 27 additional studies. Review methods The search strategy was designed to retrieve cross sectional and prospective studies of the association between long working hours and alcohol use. Summary estimates were obtained with random effects meta-analysis. Sources of heterogeneity were examined with meta-regression. Results Cross sectional analysis was based on 61 studies representing 333 693 participants from 14 countries. Prospective analysis was based on 20 studies representing 100 602 participants from nine countries. The pooled maximum adjusted odds ratio for the association between long working hours and alcohol use was 1.11 (95% confidence interval 1.05 to 1.18) in the cross sectional analysis of published and unpublished data. Odds ratio of new onset risky alcohol use was 1.12 (1.04 to 1.20) in the analysis of prospective published and unpublished data. In the 18 studies with individual participant data it was possible to assess the European Union Working Time Directive, which recommends an upper limit of 48 hours a week. Odds ratios of new onset risky alcohol use for those working 49-54 hours and ≥55 hours a week were 1.13 (1.02 to 1.26; adjusted difference in incidence 0.8 percentage points) and 1.12 (1.01 to 1.25; adjusted difference in incidence 0.7 percentage points), respectively, compared with working standard 35-40 hours (incidence of new onset risky alcohol use 6.2%). There was no difference in these associations between men and women or by age or socioeconomic groups, geographical regions, sample type (population based v occupational cohort), prevalence of risky alcohol use in the cohort, or sample attrition rate. Conclusions Individuals whose working hours exceed standard recommendations are more likely to increase their alcohol use to levels that pose a health risk. PMID:25587065

Long working hours and alcohol use: systematic review and meta-analysis of published studies and unpublished individual participant data.

PubMed

Virtanen, Marianna; Jokela, Markus; Nyberg, Solja T; Madsen, Ida E H; Lallukka, Tea; Ahola, Kirsi; Alfredsson, Lars; Batty, G David; Bjorner, Jakob B; Borritz, Marianne; Burr, Hermann; Casini, Annalisa; Clays, Els; De Bacquer, Dirk; Dragano, Nico; Erbel, Raimund; Ferrie, Jane E; Fransson, Eleonor I; Hamer, Mark; Heikkilä, Katriina; Jöckel, Karl-Heinz; Kittel, France; Knutsson, Anders; Koskenvuo, Markku; Ladwig, Karl-Heinz; Lunau, Thorsten; Nielsen, Martin L; Nordin, Maria; Oksanen, Tuula; Pejtersen, Jan H; Pentti, Jaana; Rugulies, Reiner; Salo, Paula; Schupp, Jürgen; Siegrist, Johannes; Singh-Manoux, Archana; Steptoe, Andrew; Suominen, Sakari B; Theorell, Töres; Vahtera, Jussi; Wagner, Gert G; Westerholm, Peter J M; Westerlund, Hugo; Kivimäki, Mika

2015-01-13

To quantify the association between long working hours and alcohol use. Systematic review and meta-analysis of published studies and unpublished individual participant data. A systematic search of PubMed and Embase databases in April 2014 for published studies, supplemented with manual searches. Unpublished individual participant data were obtained from 27 additional studies. The search strategy was designed to retrieve cross sectional and prospective studies of the association between long working hours and alcohol use. Summary estimates were obtained with random effects meta-analysis. Sources of heterogeneity were examined with meta-regression. Cross sectional analysis was based on 61 studies representing 333,693 participants from 14 countries. Prospective analysis was based on 20 studies representing 100,602 participants from nine countries. The pooled maximum adjusted odds ratio for the association between long working hours and alcohol use was 1.11 (95% confidence interval 1.05 to 1.18) in the cross sectional analysis of published and unpublished data. Odds ratio of new onset risky alcohol use was 1.12 (1.04 to 1.20) in the analysis of prospective published and unpublished data. In the 18 studies with individual participant data it was possible to assess the European Union Working Time Directive, which recommends an upper limit of 48 hours a week. Odds ratios of new onset risky alcohol use for those working 49-54 hours and ≥ 55 hours a week were 1.13 (1.02 to 1.26; adjusted difference in incidence 0.8 percentage points) and 1.12 (1.01 to 1.25; adjusted difference in incidence 0.7 percentage points), respectively, compared with working standard 35-40 hours (incidence of new onset risky alcohol use 6.2%). There was no difference in these associations between men and women or by age or socioeconomic groups, geographical regions, sample type (population based v occupational cohort), prevalence of risky alcohol use in the cohort, or sample attrition rate. Individuals whose working hours exceed standard recommendations are more likely to increase their alcohol use to levels that pose a health risk. © Virtanen et al 2015.

Open reading frames associated with cancer in the dark matter of the human genome.

PubMed

Delgado, Ana Paula; Brandao, Pamela; Chapado, Maria Julia; Hamid, Sheilin; Narayanan, Ramaswamy

2014-01-01

The uncharacterized proteins (open reading frames, ORFs) in the human genome offer an opportunity to discover novel targets for cancer. A systematic analysis of the dark matter of the human proteome for druggability and biomarker discovery is crucial to mining the genome. Numerous data mining tools are available to mine these ORFs to develop a comprehensive knowledge base for future target discovery and validation. Using the Genetic Association Database, the ORFs of the human dark matter proteome were screened for evidence of association with neoplasms. The Phenome-Genome Integrator tool was used to establish phenotypic association with disease traits including cancer. Batch analysis of the tools for protein expression analysis, gene ontology and motifs and domains was used to characterize the ORFs. Sixty-two ORFs were identified for neoplasm association. The expression Quantitative Trait Loci (eQTL) analysis identified thirteen ORFs related to cancer traits. Protein expression, motifs and domain analysis and genome-wide association studies verified the relevance of these OncoORFs in diverse tumors. The OncoORFs are also associated with a wide variety of human diseases and disorders. Our results link the OncoORFs to diverse diseases and disorders. This suggests a complex landscape of the uncharacterized proteome in human diseases. These results open the dark matter of the proteome to novel cancer target research. Copyright© 2014, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

A genome-wide analysis of the response to inhaled β2-agonists in chronic obstructive pulmonary disease.

PubMed

Hardin, M; Cho, M H; McDonald, M-L; Wan, E; Lomas, D A; Coxson, H O; MacNee, W; Vestbo, J; Yates, J C; Agusti, A; Calverley, P M A; Celli, B; Crim, C; Rennard, S; Wouters, E; Bakke, P; Bhatt, S P; Kim, V; Ramsdell, J; Regan, E A; Make, B J; Hokanson, J E; Crapo, J D; Beaty, T H; Hersh, C P

2016-08-01

Short-acting β2-agonist bronchodilators are the most common medications used in treating chronic obstructive pulmonary disease (COPD). Genetic variants determining bronchodilator responsiveness (BDR) in COPD have not been identified. We performed a genome-wide association study (GWAS) of BDR in 5789 current or former smokers with COPD in one African-American and four white populations. BDR was defined as the quantitative spirometric response to inhaled β2-agonists. We combined results in a meta-analysis. In the meta-analysis, single-nucleotide polymorphisms (SNPs) in the genes KCNK1 (P=2.02 × 10(-7)) and KCNJ2 (P=1.79 × 10(-7)) were the top associations with BDR. Among African Americans, SNPs in CDH13 were significantly associated with BDR (P=5.1 × 10(-9)). A nominal association with CDH13 was identified in a gene-based analysis in all subjects. We identified suggestive association with BDR among COPD subjects for variants near two potassium channel genes (KCNK1 and KCNJ2). SNPs in CDH13 were significantly associated with BDR in African Americans.The Pharmacogenomics Journal advance online publication, 27 October 2015; doi:10.1038/tpj.2015.65.

Association between the BRCA2 rs144848 polymorphism and cancer susceptibility: a meta-analysis.

PubMed

Li, Qiuyan; Guan, Rongwei; Qiao, Yuandong; Liu, Chang; He, Ning; Zhang, Xuelong; Jia, Xueyuan; Sun, Haiming; Yu, Jingcui; Xu, Lidan

2017-06-13

The BRCA2 gene plays an important role in cancer carcinogenesis, and polymorphisms in this gene have been associated with cancer risk. The BRCA2 rs144848 polymorphism has been associated with several cancers, but results have been inconsistent. In the present study, a meta-analysis was performed to assess the association between the rs144848 polymorphism and cancer risk. Literature was searched from the databases of PubMed, Embase and Google Scholar before April 2016. The fixed or random effects model was used to calculate pooled odd ratios on the basis of heterogeneity. Meta-regression, sensitivity analysis, subgroup analysis and publication bias assessment were also performed using STATA 11.0 software according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009. A total of 40 relevant studies from 30 publications including 34,911 cases and 48,329 controls were included in the final meta-analysis. Among them, 22 studies focused on breast cancer, seven on ovarian cancer, five on non-Hodgkin lymphoma, and the remaining six studies examined various other cancers. The meta-analysis results showed that there were significant associations between the rs144848 polymorphism and cancer risk in all genetic models. Stratified by cancer type, the rs144848 polymorphism was associated with non-Hodgkin lymphoma. Stratified by study design, the allele model was associated with breast cancer risk in population-based studies. The meta-analysis suggests that the BRCA2 rs144848 polymorphism may play a role in cancer risk. Further well-designed studies are warranted to confirm these results.

Efficient genome-wide association in biobanks using topic modeling identifies multiple novel disease loci.

PubMed

McCoy, Thomas H; Castro, Victor M; Snapper, Leslie A; Hart, Kamber L; Perlis, Roy H

2017-08-31

Biobanks and national registries represent a powerful tool for genomic discovery, but rely on diagnostic codes that may be unreliable and fail to capture the relationship between related diagnoses. We developed an efficient means of conducting genome-wide association studies using combinations of diagnostic codes from electronic health records (EHR) for 10845 participants in a biobanking program at two large academic medical centers. Specifically, we applied latent Dirichilet allocation to fit 50 disease topics based on diagnostic codes, then conducted genome-wide common-variant association for each topic. In sensitivity analysis, these results were contrasted with those obtained from traditional single-diagnosis phenome-wide association analysis, as well as those in which only a subset of diagnostic codes are included per topic. In meta-analysis across three biobank cohorts, we identified 23 disease-associated loci with p<1e-15, including previously associated autoimmune disease loci. In all cases, observed significant associations were of greater magnitude than for single phenome-wide diagnostic codes, and incorporation of less strongly-loading diagnostic codes enhanced association. This strategy provides a more efficient means of phenome-wide association in biobanks with coded clinical data.

Efficient Genome-wide Association in Biobanks Using Topic Modeling Identifies Multiple Novel Disease Loci

PubMed Central

McCoy, Thomas H; Castro, Victor M; Snapper, Leslie A; Hart, Kamber L; Perlis, Roy H

2017-01-01

Biobanks and national registries represent a powerful tool for genomic discovery, but rely on diagnostic codes that can be unreliable and fail to capture relationships between related diagnoses. We developed an efficient means of conducting genome-wide association studies using combinations of diagnostic codes from electronic health records for 10,845 participants in a biobanking program at two large academic medical centers. Specifically, we applied latent Dirichilet allocation to fit 50 disease topics based on diagnostic codes, then conducted a genome-wide common-variant association for each topic. In sensitivity analysis, these results were contrasted with those obtained from traditional single-diagnosis phenome-wide association analysis, as well as those in which only a subset of diagnostic codes were included per topic. In meta-analysis across three biobank cohorts, we identified 23 disease-associated loci with p < 1e-15, including previously associated autoimmune disease loci. In all cases, observed significant associations were of greater magnitude than single phenome-wide diagnostic codes, and incorporation of less strongly loading diagnostic codes enhanced association. This strategy provides a more efficient means of identifying phenome-wide associations in biobanks with coded clinical data. PMID:28861588

Association of Genetic Variants Related to Serum Calcium Levels With Coronary Artery Disease and Myocardial Infarction.

PubMed

Larsson, Susanna C; Burgess, Stephen; Michaëlsson, Karl

2017-07-25

Serum calcium has been associated with cardiovascular disease in observational studies and evidence from randomized clinical trials indicates that calcium supplementation, which raises serum calcium levels, may increase the risk of cardiovascular events, particularly myocardial infarction. To evaluate the potential causal association between genetic variants related to elevated serum calcium levels and risk of coronary artery disease (CAD) and myocardial infarction using mendelian randomization. The analyses were performed using summary statistics obtained for single-nucleotide polymorphisms (SNPs) identified from a genome-wide association meta-analysis of serum calcium levels (N = up to 61 079 individuals) and from the Coronary Artery Disease Genome-wide Replication and Meta-analysis Plus the Coronary Artery Disease Genetics (CardiogramplusC4D) consortium's 1000 genomes-based genome-wide association meta-analysis (N = up to 184 305 individuals) that included cases (individuals with CAD and myocardial infarction) and noncases, with baseline data collected from 1948 and populations derived from across the globe. The association of each SNP with CAD and myocardial infarction was weighted by its association with serum calcium, and estimates were combined using an inverse-variance weighted meta-analysis. Genetic risk score based on genetic variants related to elevated serum calcium levels. Co-primary outcomes were the odds of CAD and myocardial infarction. Among the mendelian randomized analytic sample of 184 305 individuals (60 801 CAD cases [approximately 70% with myocardial infarction] and 123 504 noncases), the 6 SNPs related to serum calcium levels and without pleiotropic associations with potential confounders were estimated to explain about 0.8% of the variation in serum calcium levels. In the inverse-variance weighted meta-analysis (combining the estimates of the 6 SNPs), the odds ratios per 0.5-mg/dL increase (about 1 SD) in genetically predicted serum calcium levels were 1.25 (95% CI, 1.08-1.45; P = .003) for CAD and 1.24 (95% CI, 1.05-1.46; P = .009) for myocardial infarction. A genetic predisposition to higher serum calcium levels was associated with increased risk of CAD and myocardial infarction. Whether the risk of CAD associated with lifelong genetic exposure to increased serum calcium levels can be translated to a risk associated with short-term to medium-term calcium supplementation is unknown.

The Human Blood Metabolome-Transcriptome Interface

PubMed Central

Schramm, Katharina; Adamski, Jerzy; Gieger, Christian; Herder, Christian; Carstensen, Maren; Peters, Annette; Rathmann, Wolfgang; Roden, Michael; Strauch, Konstantin; Suhre, Karsten; Kastenmüller, Gabi; Prokisch, Holger; Theis, Fabian J.

2015-01-01

Biological systems consist of multiple organizational levels all densely interacting with each other to ensure function and flexibility of the system. Simultaneous analysis of cross-sectional multi-omics data from large population studies is a powerful tool to comprehensively characterize the underlying molecular mechanisms on a physiological scale. In this study, we systematically analyzed the relationship between fasting serum metabolomics and whole blood transcriptomics data from 712 individuals of the German KORA F4 cohort. Correlation-based analysis identified 1,109 significant associations between 522 transcripts and 114 metabolites summarized in an integrated network, the ‘human blood metabolome-transcriptome interface’ (BMTI). Bidirectional causality analysis using Mendelian randomization did not yield any statistically significant causal associations between transcripts and metabolites. A knowledge-based interpretation and integration with a genome-scale human metabolic reconstruction revealed systematic signatures of signaling, transport and metabolic processes, i.e. metabolic reactions mainly belonging to lipid, energy and amino acid metabolism. Moreover, the construction of a network based on functional categories illustrated the cross-talk between the biological layers at a pathway level. Using a transcription factor binding site enrichment analysis, this pathway cross-talk was further confirmed at a regulatory level. Finally, we demonstrated how the constructed networks can be used to gain novel insights into molecular mechanisms associated to intermediate clinical traits. Overall, our results demonstrate the utility of a multi-omics integrative approach to understand the molecular mechanisms underlying both normal physiology and disease. PMID:26086077

Multi-omics Based Identification of Specific Biochemical Changes Associated With PfKelch13-Mutant Artemisinin-Resistant Plasmodium falciparum.

PubMed

Siddiqui, Ghizal; Srivastava, Anubhav; Russell, Adrian S; Creek, Darren J

2017-05-01

The emergence of artemisinin resistance in the malaria parasite Plasmodium falciparum poses a major threat to the control and elimination of malaria. Certain point mutations in the propeller domain of PfKelch13 are associated with resistance, but PfKelch13 mutations do not always result in clinical resistance. The underlying mechanisms associated with artemisinin resistance are poorly understood, and the impact of PfKelch13 mutations on cellular biochemistry is not defined. This study aimed to identify global biochemical differences between PfKelch13-mutant artemisinin-resistant and -sensitive strains of P. falciparum by combining liquid chromatography-mass spectrometry (LC-MS)-based proteomics, peptidomics, and metabolomics. Proteomics analysis found both PfKelch13 mutations examined to be specifically associated with decreased abundance of PfKelch13 protein. Metabolomics analysis demonstrated accumulation of glutathione and its precursor, gamma-glutamylcysteine, and significant depletion of 1 other putative metabolite in resistant strains. Peptidomics analysis revealed lower abundance of several endogenous peptides derived from hemoglobin (HBα and HBβ) in the artemisinin-resistant strains. PfKelch13 mutations associated with artemisinin resistance lead to decreased abundance of PfKelch13 protein, decreased hemoglobin digestion, and enhanced glutathione production. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Nonlinear dynamic-based analysis of severe dysphonia in patients with vocal fold scar and sulcus vocalis

PubMed Central

Choi, Seong Hee; Zhang, Yu; Jiang, Jack J.; Bless, Diane M.; Welham, Nathan V.

2011-01-01

Objective The primary goal of this study was to evaluate a nonlinear dynamic approach to the acoustic analysis of dysphonia associated with vocal fold scar and sulcus vocalis. Study Design Case-control study. Methods Acoustic voice samples from scar/sulcus patients and age/sex-matched controls were analyzed using correlation dimension (D2) and phase plots, time-domain based perturbation indices (jitter, shimmer, signal-to-noise ratio [SNR]), and an auditory-perceptual rating scheme. Signal typing was performed to identify samples with bifurcations and aperiodicity. Results Type 2 and 3 acoustic signals were highly represented in the scar/sulcus patient group. When data were analyzed irrespective of signal type, all perceptual and acoustic indices successfully distinguished scar/sulcus patients from controls. Removal of type 2 and 3 signals eliminated the previously identified differences between experimental groups for all acoustic indices except D2. The strongest perceptual-acoustic correlation in our dataset was observed for SNR; the weakest correlation was observed for D2. Conclusions These findings suggest that D2 is inferior to time-domain based perturbation measures for the analysis of dysphonia associated with scar/sulcus; however, time-domain based algorithms are inherently susceptible to inflation under highly aperiodic (i.e., type 2 and 3) signal conditions. Auditory-perceptual analysis, unhindered by signal aperiodicity, is therefore a robust strategy for distinguishing scar/sulcus patient voices from normal voices. Future acoustic analysis research in this area should consider alternative (e.g., frequency- and quefrency-domain based) measures alongside additional nonlinear approaches. PMID:22516315

Illustrating, Quantifying, and Correcting for Bias in Post-hoc Analysis of Gene-Based Rare Variant Tests of Association

PubMed Central

Grinde, Kelsey E.; Arbet, Jaron; Green, Alden; O'Connell, Michael; Valcarcel, Alessandra; Westra, Jason; Tintle, Nathan

2017-01-01

To date, gene-based rare variant testing approaches have focused on aggregating information across sets of variants to maximize statistical power in identifying genes showing significant association with diseases. Beyond identifying genes that are associated with diseases, the identification of causal variant(s) in those genes and estimation of their effect is crucial for planning replication studies and characterizing the genetic architecture of the locus. However, we illustrate that straightforward single-marker association statistics can suffer from substantial bias introduced by conditioning on gene-based test significance, due to the phenomenon often referred to as “winner's curse.” We illustrate the ramifications of this bias on variant effect size estimation and variant prioritization/ranking approaches, outline parameters of genetic architecture that affect this bias, and propose a bootstrap resampling method to correct for this bias. We find that our correction method significantly reduces the bias due to winner's curse (average two-fold decrease in bias, p < 2.2 × 10−6) and, consequently, substantially improves mean squared error and variant prioritization/ranking. The method is particularly helpful in adjustment for winner's curse effects when the initial gene-based test has low power and for relatively more common, non-causal variants. Adjustment for winner's curse is recommended for all post-hoc estimation and ranking of variants after a gene-based test. Further work is necessary to continue seeking ways to reduce bias and improve inference in post-hoc analysis of gene-based tests under a wide variety of genetic architectures. PMID:28959274

Remote sensing and spatial analysis based study for detecting deforestation and the associated drivers

NASA Astrophysics Data System (ADS)

El-Abbas, Mustafa M.; Csaplovics, Elmar; Deafalla, Taisser H.

2013-10-01

Nowadays, remote-sensing technologies are becoming increasingly interlinked to the issue of deforestation. They offer a systematized and objective strategy to document, understand and simulate the deforestation process and its associated causes. In this context, the main goal of this study, conducted in the Blue Nile region of Sudan, in which most of the natural habitats were dramatically destroyed, was to develop spatial methodologies to assess the deforestation dynamics and its associated factors. To achieve that, optical multispectral satellite scenes (i.e., ASTER and LANDSAT) integrated with field survey in addition to multiple data sources were used for the analyses. Spatiotemporal Object Based Image Analysis (STOBIA) was applied to assess the change dynamics within the period of study. Broadly, the above mentioned analyses include; Object Based (OB) classifications, post-classification change detection, data fusion, information extraction and spatial analysis. Hierarchical multi-scale segmentation thresholds were applied and each class was delimited with semantic meanings by a set of rules associated with membership functions. Consequently, the fused multi-temporal data were introduced to create detailed objects of change classes from the input LU/LC classes. The dynamic changes were quantified and spatially located as well as the spatial and contextual relations from adjacent areas were analyzed. The main finding of the present study is that, the forest areas were drastically decreased, while the agrarian structure in conversion of forest into agricultural fields and grassland was the main force of deforestation. In contrast, the capability of the area to recover was clearly observed. The study concludes with a brief assessment of an 'oriented' framework, focused on the alarming areas where serious dynamics are located and where urgent plans and interventions are most critical, guided with potential solutions based on the identified driving forces.

Reduced Flexibility Associated with Metabolic Syndrome in Community-Dwelling Elders

PubMed Central

Chang, Ke-Vin; Hung, Chen-Yu; Li, Chia-Ming; Lin, Yu-Hung; Wang, Tyng-Guey; Tsai, Keh-Sung; Han, Der-Sheng

2015-01-01

Background The ageing process may lead to reductions in physical fitness, a known risk factor in the development of metabolic syndrome. The purpose of the current study was to evaluate cross-sectional and combined associations of metabolic syndrome with body composition and physical fitness in a community based geriatric population. Methods A total of 628 community-dwelling elders attending a geriatric health examination were enrolled in the study. The diagnosis of metabolic syndrome was based on the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criterion with Asian cutoff of waist girth was adopted in this study. Body composition was obtained using bioimpedance analysis, and physical fitness was evaluated through the measurement of muscle strength (handgrip force), lower extremity muscle endurance (sit-to-stand test), flexibility (sit-and-reach test), and cardiorespiratory endurance (2-minute step test). Multivariable logistic regression and correlation analysis were performed to determine the association of metabolic syndrome with body composition and functionality variables. Results Metabolic syndrome was associated with increased skeletal muscle index (SMI) (odds ratio (OR), 1.61, 95% confidence interval (CI), 1.25–2.07) and decreased flexibility (OR, 0.97, 95% CI, 0.95–0.99) compared with those without metabolic syndrome. When body mass index was accounted for in the analysis, the association of SMI with metabolic syndrome was reduced. Waist circumference was positively correlated with SMI but negatively correlated with flexibility, whereas high density lipoprotein was positively correlated with flexibility but negatively correlated with SMI. Conclusion Reduced flexibility was positively associated with metabolic syndrome independent of age, gender, body composition, and functionality measurements in a community based geriatric population. Significant associations between metabolic syndrome with muscle strength and cardiorespiratory fitness in the elderly were not observed. Furthermore, flexibility should be included in the complete evaluation for metabolic syndrome. PMID:25614984

Inverse Association Between Gluteofemoral Obesity and Risk of Barrett's Esophagus in a Pooled Analysis.

PubMed

Kendall, Bradley J; Rubenstein, Joel H; Cook, Michael B; Vaughan, Thomas L; Anderson, Lesley A; Murray, Liam J; Shaheen, Nicholas J; Corley, Douglas A; Chandar, Apoorva K; Li, Li; Greer, Katarina B; Chak, Amitabh; El-Serag, Hashem B; Whiteman, David C; Thrift, Aaron P

2016-10-01

Gluteofemoral obesity (determined by measurement of subcutaneous fat in the hip and thigh regions) could reduce risks of cardiovascular and diabetic disorders associated with abdominal obesity. We evaluated whether gluteofemoral obesity also reduces the risk of Barrett's esophagus (BE), a premalignant lesion associated with abdominal obesity. We collected data from non-Hispanic white participants in 8 studies in the Barrett's and Esophageal Adenocarcinoma Consortium. We compared measures of hip circumference (as a proxy for gluteofemoral obesity) from cases of BE (n = 1559) separately with 2 control groups: 2557 population-based controls and 2064 individuals with gastroesophageal reflux disease (GERD controls). Study-specific odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using individual participant data and multivariable logistic regression and combined using a random-effects meta-analysis. We found an inverse relationship between hip circumference and BE (OR per 5-cm increase, 0.88; 95% CI, 0.81-0.96), compared with population-based controls in a multivariable model that included waist circumference. This association was not observed in models that did not include waist circumference. Similar results were observed in analyses stratified by frequency of GERD symptoms. The inverse association with hip circumference was statistically significant only among men (vs population-based controls: OR, 0.85; 95% CI, 0.76-0.96 for men; OR, 0.93; 95% CI, 0.74-1.16 for women). For men, within each category of waist circumference, a larger hip circumference was associated with a decreased risk of BE. Increasing waist circumference was associated with an increased risk of BE in the mutually adjusted population-based and GERD control models. Although abdominal obesity is associated with an increased risk of BE, there is an inverse association between gluteofemoral obesity and BE, particularly among men. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Exome-chip meta-analysis identifies association between variation in ANKRD26 and platelet aggregation.

PubMed

Chen, Ming-Huei; Yanek, Lisa R; Backman, Joshua D; Eicher, John D; Huffman, Jennifer E; Ben-Shlomo, Yoav; Beswick, Andrew D; Yerges-Armstrong, Laura M; Shuldiner, Alan R; O'Connell, Jeffrey R; Mathias, Rasika A; Becker, Diane M; Becker, Lewis C; Lewis, Joshua P; Johnson, Andrew D; Faraday, Nauder

2017-11-29

Previous genome-wide association studies (GWAS) have identified several variants associated with platelet function phenotypes; however, the proportion of variance explained by the identified variants is mostly small. Rare coding variants, particularly those with high potential for impact on protein structure/function, may have substantial impact on phenotype but are difficult to detect by GWAS. The main purpose of this study was to identify low frequency or rare variants associated with platelet function using genotype data from the Illumina HumanExome Bead Chip. Three family-based cohorts of European ancestry, including ~4,000 total subjects, comprised the discovery cohort and two independent cohorts, one of European and one of African American ancestry, were used for replication. Optical aggregometry in platelet-rich plasma was performed in all the discovery cohorts in response to adenosine diphosphate (ADP), epinephrine, and collagen. Meta-analyses were performed using both gene-based and single nucleotide variant association methods. The gene-based meta-analysis identified a significant association (P = 7.13 × 10 -7 ) between rare genetic variants in ANKRD26 and ADP-induced platelet aggregation. One of the ANKRD26 SNVs - rs191015656, encoding a threonine to isoleucine substitution predicted to alter protein structure/function, was replicated in Europeans. Aggregation increases of ~20-50% were observed in heterozygotes in all cohorts. Novel genetic signals in ABCG1 and HCP5 were also associated with platelet aggregation to ADP in meta-analyses, although only results for HCP5 could be replicated. The SNV in HCP5 intersects epigenetic signatures in CD41+ megakaryocytes suggesting a new functional role in platelet biology for HCP5. This is the first study to use gene-based association methods from SNV array genotypes to identify rare variants related to platelet function. The molecular mechanisms and pathophysiological relevance for the identified genetic associations requires further study.

Macrolide-based regimens in absence of bacterial co-infection in critically ill H1N1 patients with primary viral pneumonia.

PubMed

Martín-Loeches, I; Bermejo-Martin, J F; Vallés, J; Granada, R; Vidaur, L; Vergara-Serrano, J C; Martín, M; Figueira, J C; Sirvent, J M; Blanquer, J; Suarez, D; Artigas, A; Torres, A; Diaz, E; Rodriguez, A

2013-04-01

To determine whether macrolide-based treatment is associated with mortality in critically ill H1N1 patients with primary viral pneumonia. Secondary analysis of a prospective, observational, multicenter study conducted across 148 Intensive Care Units (ICU) in Spain. Primary viral pneumonia was present in 733 ICU patients with pandemic influenza A (H1N1) virus infection with severe respiratory failure. Macrolide-based treatment was administered to 190 (25.9 %) patients. Patients who received macrolides had chronic obstructive pulmonary disease more often, lower severity on admission (APACHE II score on ICU admission (13.1 ± 6.8 vs. 14.4 ± 7.4 points, p < 0.05), and multiple organ dysfunction syndrome less often (23.4 vs. 30.1 %, p < 0.05). Length of ICU stay in survivors was not significantly different in patients who received macrolides compared to patients who did not (10 (IQR 4-20) vs. 10 (IQR 5-20), p = 0.9). ICU mortality was 24.1 % (n = 177). Patients with macrolide-based treatment had lower ICU mortality in the univariate analysis (19.2 vs. 28.1 %, p = 0.02); however, a propensity score analysis showed no effect of macrolide-based treatment on ICU mortality (OR = 0.87; 95 % CI 0.55-1.37, p = 0.5). Moreover, the sensitivity analysis revealed very similar results (OR = 0.91; 95 % CI 0.58-1.44, p = 0.7). A separate analysis of patients under mechanical ventilation yielded similar results (OR = 0.77; 95 % CI 0.44-1.35, p = 0.4). Our results suggest that macrolide-based treatment was not associated with improved survival in critically ill H1N1 patients with primary viral pneumonia.

Evaluation of redundancy analysis to identify signatures of local adaptation.

PubMed

Capblancq, Thibaut; Luu, Keurcien; Blum, Michael G B; Bazin, Eric

2018-05-26

Ordination is a common tool in ecology that aims at representing complex biological information in a reduced space. In landscape genetics, ordination methods such as principal component analysis (PCA) have been used to detect adaptive variation based on genomic data. Taking advantage of environmental data in addition to genotype data, redundancy analysis (RDA) is another ordination approach that is useful to detect adaptive variation. This paper aims at proposing a test statistic based on RDA to search for loci under selection. We compare redundancy analysis to pcadapt, which is a nonconstrained ordination method, and to a latent factor mixed model (LFMM), which is a univariate genotype-environment association method. Individual-based simulations identify evolutionary scenarios where RDA genome scans have a greater statistical power than genome scans based on PCA. By constraining the analysis with environmental variables, RDA performs better than PCA in identifying adaptive variation when selection gradients are weakly correlated with population structure. Additionally, we show that if RDA and LFMM have a similar power to identify genetic markers associated with environmental variables, the RDA-based procedure has the advantage to identify the main selective gradients as a combination of environmental variables. To give a concrete illustration of RDA in population genomics, we apply this method to the detection of outliers and selective gradients on an SNP data set of Populus trichocarpa (Geraldes et al., 2013). The RDA-based approach identifies the main selective gradient contrasting southern and coastal populations to northern and continental populations in the northwestern American coast. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

An Ownership/Lease Cost Comparison Analysis of Heavy Equipment Motor Vehicles in Air Force Materiel Command

DTIC Science & Technology

1994-09-01

costs are the costs associated with a particular piece of equipment that do not change despite change in variable operating cost ( Horngren and Foster...The Operating and maintenance costs account for direct and indirect costs associated with their respective functions and vary with the utilization of...each vehicle. The operating direct cost includes all on-base and off- base fuel cost . Indirect operations costs account for bench 28 stock items

ARNetMiT R Package: association rules based gene co-expression networks of miRNA targets.

PubMed

Özgür Cingiz, M; Biricik, G; Diri, B

2017-03-31

miRNAs are key regulators that bind to target genes to suppress their gene expression level. The relations between miRNA-target genes enable users to derive co-expressed genes that may be involved in similar biological processes and functions in cells. We hypothesize that target genes of miRNAs are co-expressed, when they are regulated by multiple miRNAs. With the usage of these co-expressed genes, we can theoretically construct co-expression networks (GCNs) related to 152 diseases. In this study, we introduce ARNetMiT that utilize a hash based association rule algorithm in a novel way to infer the GCNs on miRNA-target genes data. We also present R package of ARNetMiT, which infers and visualizes GCNs of diseases that are selected by users. Our approach assumes miRNAs as transactions and target genes as their items. Support and confidence values are used to prune association rules on miRNA-target genes data to construct support based GCNs (sGCNs) along with support and confidence based GCNs (scGCNs). We use overlap analysis and the topological features for the performance analysis of GCNs. We also infer GCNs with popular GNI algorithms for comparison with the GCNs of ARNetMiT. Overlap analysis results show that ARNetMiT outperforms the compared GNI algorithms. We see that using high confidence values in scGCNs increase the ratio of the overlapped gene-gene interactions between the compared methods. According to the evaluation of the topological features of ARNetMiT based GCNs, the degrees of nodes have power-law distribution. The hub genes discovered by ARNetMiT based GCNs are consistent with the literature.

Do Differences in Exposures Explain the Observed Heterogeneity in PM2.5 - Mortality Associations across U.S. cities?

EPA Science Inventory

This analysis evaluates exposure factors as potential determinants of the heterogeneity in city-specific associations between PM2.5 and mortality. Exposure factor variables were created based on housing characteristics, commuting patterns, heating fuel usage, and climatic factors...

Pre-Service Teachers' Mathematics Content Knowledge: Implications for How Mathematics Is Taught in Higher Education

ERIC Educational Resources Information Center

Lowrie, Tom; Jorgensen, Robyn

2016-01-01

This investigation explored pre-service teachers' mathematics content knowledge (MCK) and beliefs associated with mathematics education practices. An Exploratory Factor Analysis, conducted on a beliefs and attitudes questionnaire, produced three common attitude factors associated with (1) inquiry-based teaching; (2) how mathematics knowledge is…

Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer

PubMed Central

Duell, Eric J.; Yu, Kai; Risch, Harvey A.; Olson, Sara H.; Kooperberg, Charles; Wolpin, Brian M.; Jiao, Li; Dong, Xiaoqun; Wheeler, Bill; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Fuchs, Charles S.; Gallinger, Steven; Gross, Myron; Hartge, Patricia; Hoover, Robert N.; Holly, Elizabeth A.; Jacobs, Eric J.; Klein, Alison P.; LaCroix, Andrea; Mandelson, Margaret T.; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Albanes, Demetrius; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Buring, Julie E.; Canzian, Federico; Chang, Kenneth; Chanock, Stephen J.; Cotterchio, Michelle; Gaziano, J.Michael; Giovannucci, Edward L.; Goggins, Michael; Hallmans, Göran; Hankinson, Susan E.; Hoffman Bolton, Judith A.; Hunter, David J.; Hutchinson, Amy; Jacobs, Kevin B.; Jenab, Mazda; Khaw, Kay-Tee; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C.; McWilliams, Robert R.; Mendelsohn, Julie B.; Patel, Alpa V.; Rabe, Kari G.; Riboli, Elio; Shu, Xiao-Ou; Tjønneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Visvanathan, Kala; Watters, Joanne; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Stolzenberg-Solomon, Rachael Z.

2012-01-01

Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic cancer cases and 3934 control participants pooled from 12 cohort studies and 8 case–control studies (PanScan). We compiled 23 biological pathways hypothesized to be relevant to pancreatic cancer and observed a nominal association between pancreatic cancer and five pathways (P < 0.05), i.e. pancreatic development, Helicobacter pylori lacto/neolacto, hedgehog, Th1/Th2 immune response and apoptosis (P = 2.0 × 10−6, 1.6 × 10−5, 0.0019, 0.019 and 0.023, respectively). After excluding previously identified genes from the original GWAS in three pathways (NR5A2, ABO and SHH), the pancreatic development pathway remained significant (P = 8.3 × 10−5), whereas the others did not. The most significant genes (P < 0.01) in the five pathways were NR5A2, HNF1A, HNF4G and PDX1 for pancreatic development; ABO for H. pylori lacto/neolacto; SHH for hedgehog; TGFBR2 and CCL18 for Th1/Th2 immune response and MAPK8 and BCL2L11 for apoptosis. Our results provide a link between inherited variation in genes important for pancreatic development and cancer and show that pathway-based approaches to analysis of GWAS data can yield important insights into the collective role of genetic risk variants in cancer. PMID:22523087

From Interaction to Co-Association —A Fisher r-To-z Transformation-Based Simple Statistic for Real World Genome-Wide Association Study

PubMed Central

Yuan, Zhongshang; Liu, Hong; Zhang, Xiaoshuai; Li, Fangyu; Zhao, Jinghua; Zhang, Furen; Xue, Fuzhong

2013-01-01

Currently, the genetic variants identified by genome wide association study (GWAS) generally only account for a small proportion of the total heritability for complex disease. One crucial reason is the underutilization of gene-gene joint effects commonly encountered in GWAS, which includes their main effects and co-association. However, gene-gene co-association is often customarily put into the framework of gene-gene interaction vaguely. From the causal graph perspective, we elucidate in detail the concept and rationality of gene-gene co-association as well as its relationship with traditional gene-gene interaction, and propose two Fisher r-to-z transformation-based simple statistics to detect it. Three series of simulations further highlight that gene-gene co-association refers to the extent to which the joint effects of two genes differs from the main effects, not only due to the traditional interaction under the nearly independent condition but the correlation between two genes. The proposed statistics are more powerful than logistic regression under various situations, cannot be affected by linkage disequilibrium and can have acceptable false positive rate as long as strictly following the reasonable GWAS data analysis roadmap. Furthermore, an application to gene pathway analysis associated with leprosy confirms in practice that our proposed gene-gene co-association concepts as well as the correspondingly proposed statistics are strongly in line with reality. PMID:23923021

[Correlation analysis between single nucleotide polymorphism of FGF5 gene and wool yield in rabbits].

PubMed

Li, Chun-Xiao; Jiang, Mei-Shan; Chen, Shi-Yi; Lai, Song-Jia

2008-07-01

Single nucleotide polymorphism (SNP) in exon 1 and 3 of fibroblast growth factor (FGF5) gene was studied by DNA sequencing in Yingjing angora rabbit, Tianfu black rabbit and California rabbit. A frameshift mutation (TCT insert) at base position 217 (site A) of exon 1 and a T/C missense mutation at base position 59 (site B) of exon 3 were found in Yingjing angora rabbit with a high frequency; a T/C same-sense mutation at base position 3 (site C) of exon 3 was found with similar frequency in three rabbit breeds. Least square analysis showed that different genotypes had no significant association with wool yield in site A, and had high significant association with wool yield in site B (P<0.01) and significant association with wool yield in site C (P<0.05). It was concluded from the results that FGF5 gene could be the potential major gene affecting wool yield or link with the major gene, and polymorphic loci B and C may be used as molecular markers for im-proving wool yield in angora rabbits.

Bivariate categorical data analysis using normal linear conditional multinomial probability model.

PubMed

Sun, Bingrui; Sutradhar, Brajendra

2015-02-10

Bivariate multinomial data such as the left and right eyes retinopathy status data are analyzed either by using a joint bivariate probability model or by exploiting certain odds ratio-based association models. However, the joint bivariate probability model yields marginal probabilities, which are complicated functions of marginal and association parameters for both variables, and the odds ratio-based association model treats the odds ratios involved in the joint probabilities as 'working' parameters, which are consequently estimated through certain arbitrary 'working' regression models. Also, this later odds ratio-based model does not provide any easy interpretations of the correlations between two categorical variables. On the basis of pre-specified marginal probabilities, in this paper, we develop a bivariate normal type linear conditional multinomial probability model to understand the correlations between two categorical variables. The parameters involved in the model are consistently estimated using the optimal likelihood and generalized quasi-likelihood approaches. The proposed model and the inferences are illustrated through an intensive simulation study as well as an analysis of the well-known Wisconsin Diabetic Retinopathy status data. Copyright © 2014 John Wiley & Sons, Ltd.

Protein Interaction Networks Reveal Novel Autism Risk Genes within GWAS Statistical Noise

PubMed Central

Correia, Catarina; Oliveira, Guiomar; Vicente, Astrid M.

2014-01-01

Genome-wide association studies (GWAS) for Autism Spectrum Disorder (ASD) thus far met limited success in the identification of common risk variants, consistent with the notion that variants with small individual effects cannot be detected individually in single SNP analysis. To further capture disease risk gene information from ASD association studies, we applied a network-based strategy to the Autism Genome Project (AGP) and the Autism Genetics Resource Exchange GWAS datasets, combining family-based association data with Human Protein-Protein interaction (PPI) data. Our analysis showed that autism-associated proteins at higher than conventional levels of significance (P<0.1) directly interact more than random expectation and are involved in a limited number of interconnected biological processes, indicating that they are functionally related. The functionally coherent networks generated by this approach contain ASD-relevant disease biology, as demonstrated by an improved positive predictive value and sensitivity in retrieving known ASD candidate genes relative to the top associated genes from either GWAS, as well as a higher gene overlap between the two ASD datasets. Analysis of the intersection between the networks obtained from the two ASD GWAS and six unrelated disease datasets identified fourteen genes exclusively present in the ASD networks. These are mostly novel genes involved in abnormal nervous system phenotypes in animal models, and in fundamental biological processes previously implicated in ASD, such as axon guidance, cell adhesion or cytoskeleton organization. Overall, our results highlighted novel susceptibility genes previously hidden within GWAS statistical “noise” that warrant further analysis for causal variants. PMID:25409314

Protein interaction networks reveal novel autism risk genes within GWAS statistical noise.

PubMed

Correia, Catarina; Oliveira, Guiomar; Vicente, Astrid M

2014-01-01

Genome-wide association studies (GWAS) for Autism Spectrum Disorder (ASD) thus far met limited success in the identification of common risk variants, consistent with the notion that variants with small individual effects cannot be detected individually in single SNP analysis. To further capture disease risk gene information from ASD association studies, we applied a network-based strategy to the Autism Genome Project (AGP) and the Autism Genetics Resource Exchange GWAS datasets, combining family-based association data with Human Protein-Protein interaction (PPI) data. Our analysis showed that autism-associated proteins at higher than conventional levels of significance (P<0.1) directly interact more than random expectation and are involved in a limited number of interconnected biological processes, indicating that they are functionally related. The functionally coherent networks generated by this approach contain ASD-relevant disease biology, as demonstrated by an improved positive predictive value and sensitivity in retrieving known ASD candidate genes relative to the top associated genes from either GWAS, as well as a higher gene overlap between the two ASD datasets. Analysis of the intersection between the networks obtained from the two ASD GWAS and six unrelated disease datasets identified fourteen genes exclusively present in the ASD networks. These are mostly novel genes involved in abnormal nervous system phenotypes in animal models, and in fundamental biological processes previously implicated in ASD, such as axon guidance, cell adhesion or cytoskeleton organization. Overall, our results highlighted novel susceptibility genes previously hidden within GWAS statistical "noise" that warrant further analysis for causal variants.

Workplace bullying and sickness absence: a systematic review and meta-analysis of the research literature.

PubMed

Nielsen, Morten Birkeland; Indregard, Anne-Marthe Rustad; Øverland, Simon

2016-09-01

The association between workplace bullying and sickness absence remains unclear. This paper presents a systematic review and meta-analysis of research on the association. We conducted a systematic review and meta-analysis of published primary studies on workplace bullying and sickness absence. Studies based on prospective design or registry data on sickness absence were included. Cross-sectional studies with self-reported sickness absence were excluded. Seventeen primary studies were included in the review, sixteen originated from the Nordic countries and fifteen included registry data on sickness absence. All but one study found that exposure to workplace bullying was associated with increased risk of sickness absence. A meta-analysis of ten independent studies showed that exposure to bullying increased the risk of sickness absence (odds ratio 1.58, 95% CI 1.39-1.79). Five studies included variables that moderated the association between bullying and absenteeism. None of the studies included mediating variables. No studies examined sickness absence as a risk factor for later exposure to bullying. Following the GRADE guidelines, the evidence for an association between bullying and sickness absence is moderate. Workplace bullying is a risk factor for sickness absence, but the mechanisms to explain this relationship are not sufficiently described. It is unclear whether sickness absence predicts later exposure to bullying. While, the methodological quality of the reviewed studies was high, the knowledge base is small. There is a need for more research on how and when bullying is related to sickness absence and the possible bidirectional relationships involved.

Assessment of current AASHTO LRFD methods for static pile capacity analysis in Rhode Island soils.

DOT National Transportation Integrated Search

2013-07-01

This report presents an assessment of current AASHTO LRFD methods for static pile capacity analysis in Rhode : Island soils. Current static capacity methods and associated resistance factors are based on pile load test data in sands : and clays. Some...

Higher Education Students' Attitudes towards Experiential Learning in International Business

ERIC Educational Resources Information Center

Chavan, Meena

2011-01-01

Using qualitative and quantitative analysis this paper presents a teaching model based on experiential learning in a large "International Business" unit. Preliminary analysis of 92 student evaluations determined the effectiveness of experiential learning to allow students to explore the association between theory and practice. The…

MODEL UNCERTAINTY ANALYSIS, FIELD DATA COLLECTION AND ANALYSIS OF CONTAMINATED VAPOR INTRUSION INTO BUILDINGS

EPA Science Inventory

To address uncertainty associated with the evaluation of vapor intrusion problems we are working on a three part strategy that includes: evaluation of uncertainty in model-based assessments; collection of field data and assessment of sites using EPA and state protocols.

Association of personality with the development and persistence of obesity: a meta-analysis based on individual-participant data.

PubMed

Jokela, M; Hintsanen, M; Hakulinen, C; Batty, G D; Nabi, H; Singh-Manoux, A; Kivimäki, M

2013-04-01

Personality is thought to affect obesity risk but before such information can be incorporated into prevention and intervention plans, robust and converging evidence concerning the most relevant personality traits is needed. We performed a meta-analysis based on individual-participant data from nine cohort studies to examine whether broad-level personality traits predict the development and persistence of obesity (n = 78,931 men and women; mean age 50 years). Personality was assessed using inventories of the Five-Factor Model (extraversion, neuroticism, agreeableness, conscientiousness and openness to experience). High conscientiousness - reflecting high self-control, orderliness and adherence to social norms - was associated with lower obesity risk across studies (pooled odds ratio [OR] = 0.84; 95% confidence interval [CI] = 0.80-0.88 per 1 standard deviation increment in conscientiousness). Over a mean follow-up of 5.4 years, conscientiousness predicted lower obesity risk in initially non-obese individuals (OR = 0.88, 95% CI = 0.85-0.92; n = 33,981) and was associated with greater likelihood of reversion to non-obese among initially obese individuals (OR = 1.08, 95% CI = 1.01-1.14; n = 9,657). Other personality traits were not associated with obesity in the pooled analysis, and there was substantial heterogeneity in the associations between studies. The findings indicate that conscientiousness may be the only broad-level personality trait of the Five-Factor Model that is consistently associated with obesity across populations. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.

Association of Body Mass Index With Self-Report and Performance-Based Measures of Balance and Mobility

PubMed Central

Wert, David M.; Hile, Elizabeth S.; Studenski, Stephanie A.; Brach, Jennifer S.

2011-01-01

Background The incidence of obesity is increasing in older adults, with associated worsening in the burden of disability. Little is known about the impact of body mass index (BMI) on self-report and performance-based balance and mobility measures in older adults. Objective The purposes of this study were (1) to examine the association of BMI with measures of balance and mobility and (2) to explore potential explanatory factors. Design This was a cross-sectional, observational study. Methods Older adults (mean age=77.6 years) who participated in an ongoing observational study (N=120) were classified as normal weight (BMI=18.5–24.9 kg/m2), overweight (BMI=25.0–29.9 kg/m2), moderately obese (BMI=30.0–34.9 kg/m2), or severely obese (BMI≥35 kg/m2). Body mass index data were missing for one individual; thus, data for 119 participants were included in the analysis. Mobility and balance were assessed using self-report and performance-based measures and were compared among weight groups using analysis of variance and chi-square analysis for categorical data. Multiple linear regression analysis was used to examine the association among BMI, mobility, and balance after controlling for potential confounding variables. Results Compared with participants who were of normal weight or overweight, those with moderate or severe obesity were less likely to report their mobility as very good or excellent (52%, 55%, 39%, and 6%, respectively); however, there was no difference in self-report of balance among weight groups. Participants with severe obesity (n=17) had the lowest levels of mobility on the performance-based measures, followed by those who were moderately obese (n=31), overweight (n=42), and of normal weight (n=29). There were no differences on performance-based balance measures among weight groups. After controlling for age, sex, minority status, physical activity level, education level, and comorbid conditions, BMI still significantly contributed to mobility (β=−.02, adjusted R2=.41). Conclusions Although older adults with severe obesity were most impaired, those with less severe obesity also demonstrated significant decrements in mobility. PMID:21680770

Association analysis of rare variants near the APOE region with CSF and neuroimaging biomarkers of Alzheimer's disease.

PubMed

Nho, Kwangsik; Kim, Sungeun; Horgusluoglu, Emrin; Risacher, Shannon L; Shen, Li; Kim, Dokyoon; Lee, Seunggeun; Foroud, Tatiana; Shaw, Leslie M; Trojanowski, John Q; Aisen, Paul S; Petersen, Ronald C; Jack, Clifford R; Weiner, Michael W; Green, Robert C; Toga, Arthur W; Saykin, Andrew J

2017-05-24

The APOE ε4 allele is the most significant common genetic risk factor for late-onset Alzheimer's disease (LOAD). The region surrounding APOE on chromosome 19 has also shown consistent association with LOAD. However, no common variants in the region remain significant after adjusting for APOE genotype. We report a rare variant association analysis of genes in the vicinity of APOE with cerebrospinal fluid (CSF) and neuroimaging biomarkers of LOAD. Whole genome sequencing (WGS) was performed on 817 blood DNA samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sequence data from 757 non-Hispanic Caucasian participants was used in the present analysis. We extracted all rare variants (MAF (minor allele frequency) < 0.05) within a 312 kb window in APOE's vicinity encompassing 12 genes. We assessed CSF and neuroimaging (MRI and PET) biomarkers as LOAD-related quantitative endophenotypes. Gene-based analyses of rare variants were performed using the optimal Sequence Kernel Association Test (SKAT-O). A total of 3,334 rare variants (MAF < 0.05) were found within the APOE region. Among them, 72 rare non-synonymous variants were observed. Eight genes spanning the APOE region were significantly associated with CSF Aβ 1-42 (p < 1.0 × 10 -3 ). After controlling for APOE genotype and adjusting for multiple comparisons, 4 genes (CBLC, BCAM, APOE, and RELB) remained significant. Whole-brain surface-based analysis identified highly significant clusters associated with rare variants of CBLC in the temporal lobe region including the entorhinal cortex, as well as frontal lobe regions. Whole-brain voxel-wise analysis of amyloid PET identified significant clusters in the bilateral frontal and parietal lobes showing associations of rare variants of RELB with cortical amyloid burden. Rare variants within genes spanning the APOE region are significantly associated with LOAD-related CSF Aβ 1-42 and neuroimaging biomarkers after adjusting for APOE genotype. These findings warrant further investigation and illustrate the role of next generation sequencing and quantitative endophenotypes in assessing rare variants which may help explain missing heritability in AD and other complex diseases.

Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: protocol for a collaborative meta-analysis.

PubMed

Hartwig, Fernando Pires; Davies, Neil Martin; Horta, Bernardo Lessa; Victora, Cesar Gomes; Davey Smith, George

2016-06-15

Evidence from observational studies and randomised controlled trials suggests that breastfeeding is positively associated with IQ, possibly because breast milk is a source of long-chain polyunsaturated fatty acids. Different studies have detected gene-breastfeeding interactions involving FADS2 variants and intelligence. However, findings are inconsistent regarding the direction of such effect modification. To clarify how FADS2 and breastfeeding interact in their association with IQ, we are conducting a consortium-based meta-analysis of independent studies. Results produced by each individual study using standardised analysis scripts and harmonised data will be used. breastfeeding, IQ and either rs174575 or rs1535 polymorphisms available; and being of European ancestry. twin studies; only poorly imputed genetic data available; or unavailability of proper ethics approval. Studies will be invited based on being known to have at least some of the required data, or suggested by participating studies as potentially eligible. This inclusive approach will favour achieving a larger sample size and be less prone to publication bias. Improving current understanding of FADS2-breastfeeding interaction may provide important biological insights regarding the importance of long-chain polyunsaturated fatty acids for the breastfeeding-IQ association. This meta-analysis will help to improve such knowledge by replicating earlier studies, conducting additional analysis and evaluating different sources of heterogeneity. Publishing this protocol will minimise the possibility of bias due to post hoc changes to the analysis protocol. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Joint association discovery and diagnosis of Alzheimer's disease by supervised heterogeneous multiview learning.

PubMed

Zhe, Shandian; Xu, Zenglin; Qi, Yuan; Yu, Peng

2014-01-01

A key step for Alzheimer's disease (AD) study is to identify associations between genetic variations and intermediate phenotypes (e.g., brain structures). At the same time, it is crucial to develop a noninvasive means for AD diagnosis. Although these two tasks-association discovery and disease diagnosis-have been treated separately by a variety of approaches, they are tightly coupled due to their common biological basis. We hypothesize that the two tasks can potentially benefit each other by a joint analysis, because (i) the association study discovers correlated biomarkers from different data sources, which may help improve diagnosis accuracy, and (ii) the disease status may help identify disease-sensitive associations between genetic variations and MRI features. Based on this hypothesis, we present a new sparse Bayesian approach for joint association study and disease diagnosis. In this approach, common latent features are extracted from different data sources based on sparse projection matrices and used to predict multiple disease severity levels based on Gaussian process ordinal regression; in return, the disease status is used to guide the discovery of relationships between the data sources. The sparse projection matrices not only reveal the associations but also select groups of biomarkers related to AD. To learn the model from data, we develop an efficient variational expectation maximization algorithm. Simulation results demonstrate that our approach achieves higher accuracy in both predicting ordinal labels and discovering associations between data sources than alternative methods. We apply our approach to an imaging genetics dataset of AD. Our joint analysis approach not only identifies meaningful and interesting associations between genetic variations, brain structures, and AD status, but also achieves significantly higher accuracy for predicting ordinal AD stages than the competing methods.

Capillary electrophoresis for the analysis of contaminants in emerging food safety issues and food traceability.

PubMed

Vallejo-Cordoba, Belinda; González-Córdova, Aarón F

2010-07-01

This review presents an overview of the applicability of CE in the analysis of chemical and biological contaminants involved in emerging food safety issues. Additionally, CE-based genetic analyzers' usefulness as a unique tool in food traceability verification systems was presented. First, analytical approaches for the determination of melamine and specific food allergens in different foods were discussed. Second, natural toxin analysis by CE was updated from the last review reported in 2008. Finally, the analysis of prion proteins associated with the "mad cow" crises and the application of CE-based genetic analyzers for meat traceability were summarized.

A practical guide to environmental association analysis in landscape genomics.

PubMed

Rellstab, Christian; Gugerli, Felix; Eckert, Andrew J; Hancock, Angela M; Holderegger, Rolf

2015-09-01

Landscape genomics is an emerging research field that aims to identify the environmental factors that shape adaptive genetic variation and the gene variants that drive local adaptation. Its development has been facilitated by next-generation sequencing, which allows for screening thousands to millions of single nucleotide polymorphisms in many individuals and populations at reasonable costs. In parallel, data sets describing environmental factors have greatly improved and increasingly become publicly accessible. Accordingly, numerous analytical methods for environmental association studies have been developed. Environmental association analysis identifies genetic variants associated with particular environmental factors and has the potential to uncover adaptive patterns that are not discovered by traditional tests for the detection of outlier loci based on population genetic differentiation. We review methods for conducting environmental association analysis including categorical tests, logistic regressions, matrix correlations, general linear models and mixed effects models. We discuss the advantages and disadvantages of different approaches, provide a list of dedicated software packages and their specific properties, and stress the importance of incorporating neutral genetic structure in the analysis. We also touch on additional important aspects such as sampling design, environmental data preparation, pooled and reduced-representation sequencing, candidate-gene approaches, linearity of allele-environment associations and the combination of environmental association analyses with traditional outlier detection tests. We conclude by summarizing expected future directions in the field, such as the extension of statistical approaches, environmental association analysis for ecological gene annotation, and the need for replication and post hoc validation studies. © 2015 John Wiley & Sons Ltd.

Developmental changes in hippocampal shape among preadolescent children.

PubMed

Lin, Muqing; Fwu, Peter T; Buss, Claudia; Davis, Elysia P; Head, Kevin; Muftuler, L Tugan; Sandman, Curt A; Su, Min-Ying

2013-11-01

It is known that the largest developmental changes in the hippocampus take place during the prenatal period and during the first two years of postnatal life. Few studies have been conducted to address the normal developmental trajectory of the hippocampus during childhood. In this study shape analysis was applied to study the normal developing hippocampus in a group of 103 typically developing 6- to 10-year-old preadolescent children. The individual brain was normalized to a template, and then the hippocampus was manually segmented and further divided into the head, body, and tail sub-regions. Three different methods were applied for hippocampal shape analysis: radial distance mapping, surface-based template registration using the robust point matching (RPM) algorithm, and volume-based template registration using the Demons algorithm. All three methods show that the older children have bilateral expanded head segments compared to the younger children. The results analyzed based on radial distance to the centerline were consistent with those analyzed using template-based registration methods. In analyses stratified by sex, it was found that the age-associated anatomical changes were similar in boys and girls, but the age-association was strongest in girls. Total hippocampal volume and sub-regional volumes analyzed using manual segmentation did not show a significant age-association. Our results suggest that shape analysis is sensitive to detect sub-regional differences that are not revealed in volumetric analysis. The three methods presented in this study may be applied in future studies to investigate the normal developmental trajectory of the hippocampus in children. They may be further applied to detect early deviations from the normal developmental trajectory in young children for evaluating susceptibility for psychopathological disorders involving hippocampus. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

16 CFR 1000.26 - Directorate for Epidemiology.

Code of Federal Regulations, 2010 CFR

2010-01-01

... things, incidents associated with consumer products, based on news clips, medical examiner reports, hotline reports, Internet complaints, and referrals. The Hazard Analysis Division conducts statistical...

Dissociative Experiences are Associated with Obsessive-Compulsive Symptoms in a Non-clinical Sample: A Latent Profile Analysis

PubMed Central

BOYSAN, Murat

2014-01-01

Introduction There has been a burgeoning literature considering the significant associations between obsessive-compulsive symptoms and dissociative experiences. In this study, the relationsips between dissociative symtomotology and dimensions of obsessive-compulsive symptoms were examined in homogeneous sub-groups obtained with latent class algorithm in an undergraduate Turkish sample. Method Latent profile analysis, a recently developed classification method based on latent class analysis, was applied to the Dissociative Experiences Scale (DES) item-response data from 2976 undergraduates. Differences in severity of obsessive-compulsive symptoms, anxiety and depression across groups were evaluated by running multinomial logistic regression analyses. Associations between latent class probabilities and psychological variables in terms of obsessive-compulsive sub-types, anxiety, and depression were assessed by computing Pearson’s product-moment correlation coefficients. Results The findings of the latent profile analysis supported further evidence for discontinuity model of dissociative experiences. The analysis empirically justified the distinction among three sub-groups based on the DES items. A marked proportion of the sample (42%) was assigned to the high dissociative class. In the further analyses, all sub-types of obsessive-compulsive symptoms significantly differed across latent classes. Regarding the relationships between obsessive-compulsive symptoms and dissociative symptomatology, low dissociation appeared to be a buffering factor dealing with obsessive-compulsive symptoms; whereas high dissociation appeared to be significantly associated with high levels of obsessive-compulsive symptoms. Conclusion It is concluded that the concept of dissociation can be best understood in a typological approach that dissociative symptomatology not only exacerbates obsessive-compulsive symptoms but also serves as an adaptive coping mechanism. PMID:28360635

Dissociative Experiences are Associated with Obsessive-Compulsive Symptoms in a Non-clinical Sample: A Latent Profile Analysis.

PubMed

Boysan, Murat

2014-09-01

There has been a burgeoning literature considering the significant associations between obsessive-compulsive symptoms and dissociative experiences. In this study, the relationsips between dissociative symtomotology and dimensions of obsessive-compulsive symptoms were examined in homogeneous sub-groups obtained with latent class algorithm in an undergraduate Turkish sample. Latent profile analysis, a recently developed classification method based on latent class analysis, was applied to the Dissociative Experiences Scale (DES) item-response data from 2976 undergraduates. Differences in severity of obsessive-compulsive symptoms, anxiety and depression across groups were evaluated by running multinomial logistic regression analyses. Associations between latent class probabilities and psychological variables in terms of obsessive-compulsive sub-types, anxiety, and depression were assessed by computing Pearson's product-moment correlation coefficients. The findings of the latent profile analysis supported further evidence for discontinuity model of dissociative experiences. The analysis empirically justified the distinction among three sub-groups based on the DES items. A marked proportion of the sample (42%) was assigned to the high dissociative class. In the further analyses, all sub-types of obsessive-compulsive symptoms significantly differed across latent classes. Regarding the relationships between obsessive-compulsive symptoms and dissociative symptomatology, low dissociation appeared to be a buffering factor dealing with obsessive-compulsive symptoms; whereas high dissociation appeared to be significantly associated with high levels of obsessive-compulsive symptoms. It is concluded that the concept of dissociation can be best understood in a typological approach that dissociative symptomatology not only exacerbates obsessive-compulsive symptoms but also serves as an adaptive coping mechanism.

Herpesviruses in etiopathogenesis of aggressive periodontitis: A meta-analysis based on case-control studies.

PubMed

Li, Fei; Zhu, Ce; Deng, Feng-Ying; Wong, May Chun Mei; Lu, Hai-Xia; Feng, Xi-Ping

2017-01-01

Previous studies have found that herpesviruses are associated with aggressive periodontitis (AgP). However, these findings are controversial. This meta-analysis was aimed at clarifying the association between herpesviruses and AgP. We identified eligible case-control studies evaluating the association between herpesviruses and AgP from PubMed and Embase databases in October 2015. Original data were extracted and quality assessment was done. Overall odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Random-effects model was determined. The stability was evaluated by sensitivity analysis. Finally, Egger's funnel plot was used to investigate the publication bias. Twelve case-control studies involving 322 patients and 342 controls were included in the present meta-analysis. The included case-control studies were assessed as high quality. The quantitative synthesis results for Epstein-Barr virus (EBV) showed significance (10 studies: p = 0.0008, OR = 6.11, 95% CI = 2.13-17.51); nevertheless, evidence of publication bias for EBV was considerable (EBV: Egger's test, p<0.001). Human cytomegalovirus (HCMV) and Herpes simplex virus type 1 (HSV-1) had significant association with AgP (12 studies for HCMV: p = 0.009, OR = 3.63, 95% CI = 2.15-6.13; 4 studies for HSV-1: p<0.001, OR = 19.19, 95% CI = 4.16-79.06). Sensitivity analyses showed the results yielded consistency, and no significant publication bias was observed for HCMV. The association between Herpes simplex virus type 2 (HSV-2) and AgP was inconclusive (2 studies: p = 0.20, OR = 3.46, 95% CI = 0.51-23.51). This meta-analysis suggests that HCMV and HSV-1 are significantly associated with AgP. However, due to the heterogeneity among studies these conclusions should be cautiously interpreted. There is insufficient evidence to draw any conclusion between EBV, HSV-2 and AgP based on the currently limited data.

Application of a faith-based integration tool to assess mental and physical health interventions

PubMed Central

Saunders, Donna M.; Leak, Jean; Carver, Monique E.; Smith, Selina A.

2017-01-01

Background To build on current research involving faith-based interventions (FBIs) for addressing mental and physical health, this study a) reviewed the extent to which relevant publications integrate faith concepts with health and b) initiated analysis of the degree of FBI integration with intervention outcomes. Methods Derived from a systematic search of articles published between 2007 and 2017, 36 studies were assessed with a Faith-Based Integration Assessment Tool (FIAT) to quantify faith-health integration. Basic statistical procedures were employed to determine the association of faith-based integration with intervention outcomes. Results The assessed studies possessed (on average) moderate, inconsistent integration because of poor use of faith measures, and moderate, inconsistent use of faith practices. Analysis procedures for determining the effect of FBI integration on intervention outcomes were inadequate for formulating practical conclusions. Conclusions Regardless of integration, interventions were associated with beneficial outcomes. To determine the link between FBI integration and intervention outcomes, additional analyses are needed. PMID:29354795

Single-cell RNA sequencing reveals gene expression signatures of breast cancer-associated endothelial cells.

PubMed

Sun, Zhengda; Wang, Chih-Yang; Lawson, Devon A; Kwek, Serena; Velozo, Hugo Gonzalez; Owyong, Mark; Lai, Ming-Derg; Fong, Lawrence; Wilson, Mark; Su, Hua; Werb, Zena; Cooke, Daniel L

2018-02-16

Tumor endothelial cells (TEC) play an indispensible role in tumor growth and metastasis although much of the detailed mechanism still remains elusive. In this study we characterized and compared the global gene expression profiles of TECs and control ECs isolated from human breast cancerous tissues and reduction mammoplasty tissues respectively by single cell RNA sequencing (scRNA-seq). Based on the qualified scRNA-seq libraries that we made, we found that 1302 genes were differentially expressed between these two EC phenotypes. Both principal component analysis (PCA) and heat map-based hierarchical clustering separated the cancerous versus control ECs as two distinctive clusters, and MetaCore disease biomarker analysis indicated that these differentially expressed genes are highly correlated with breast neoplasm diseases. Gene Set Enrichment Analysis software (GSEA) enriched these genes to extracellular matrix (ECM) signal pathways and highlighted 127 ECM-associated genes. External validation verified some of these ECM-associated genes are not only generally overexpressed in various cancer tissues but also specifically overexpressed in colorectal cancer ECs and lymphoma ECs. In conclusion, our data demonstrated that ECM-associated genes play pivotal roles in breast cancer EC biology and some of them could serve as potential TEC biomarkers for various cancers.

Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis.

PubMed

Benyamin, Beben; He, Ji; Zhao, Qiongyi; Gratten, Jacob; Garton, Fleur; Leo, Paul J; Liu, Zhijun; Mangelsdorf, Marie; Al-Chalabi, Ammar; Anderson, Lisa; Butler, Timothy J; Chen, Lu; Chen, Xiang-Ding; Cremin, Katie; Deng, Hong-Weng; Devine, Matthew; Edson, Janette; Fifita, Jennifer A; Furlong, Sarah; Han, Ying-Ying; Harris, Jessica; Henders, Anjali K; Jeffree, Rosalind L; Jin, Zi-Bing; Li, Zhongshan; Li, Ting; Li, Mengmeng; Lin, Yong; Liu, Xiaolu; Marshall, Mhairi; McCann, Emily P; Mowry, Bryan J; Ngo, Shyuan T; Pamphlett, Roger; Ran, Shu; Reutens, David C; Rowe, Dominic B; Sachdev, Perminder; Shah, Sonia; Song, Sharon; Tan, Li-Jun; Tang, Lu; van den Berg, Leonard H; van Rheenen, Wouter; Veldink, Jan H; Wallace, Robyn H; Wheeler, Lawrie; Williams, Kelly L; Wu, Jinyu; Wu, Xin; Yang, Jian; Yue, Weihua; Zhang, Zong-Hong; Zhang, Dai; Noakes, Peter G; Blair, Ian P; Henderson, Robert D; McCombe, Pamela A; Visscher, Peter M; Xu, Huji; Bartlett, Perry F; Brown, Matthew A; Wray, Naomi R; Fan, Dongsheng

2017-09-20

Cross-ethnic genetic studies can leverage power from differences in disease epidemiology and population-specific genetic architecture. In particular, the differences in linkage disequilibrium and allele frequency patterns across ethnic groups may increase gene-mapping resolution. Here we use cross-ethnic genetic data in sporadic amyotrophic lateral sclerosis (ALS), an adult-onset, rapidly progressing neurodegenerative disease. We report analyses of novel genome-wide association study data of 1,234 ALS cases and 2,850 controls. We find a significant association of rs10463311 spanning GPX3-TNIP1 with ALS (p = 1.3 × 10 -8 ), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 10 -3 ). Both GPX3 and TNIP1 interact with other known ALS genes (SOD1 and OPTN, respectively). In addition, GGNBP2 was identified using gene-based analysis and summary statistics-based Mendelian randomization analysis, although further replication is needed to confirm this result. Our results increase our understanding of genetic aetiology of ALS.Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.

Social network types among older Korean adults: Associations with subjective health.

PubMed

Sohn, Sung Yun; Joo, Won-Tak; Kim, Woo Jung; Kim, Se Joo; Youm, Yoosik; Kim, Hyeon Chang; Park, Yeong-Ran; Lee, Eun

2017-01-01

With population aging now a global phenomenon, the health of older adults is becoming an increasingly important issue. Because the Korean population is aging at an unprecedented rate, preparing for public health problems associated with old age is particularly salient in this country. As the physical and mental health of older adults is related to their social relationships, investigating the social networks of older adults and their relationship to health status is important for establishing public health policies. The aims of this study were to identify social network types among older adults in South Korea and to examine the relationship of these social network types with self-rated health and depression. Data from the Korean Social Life, Health, and Aging Project were analyzed. Model-based clustering using finite normal mixture modeling was conducted to identify the social network types based on ten criterion variables of social relationships and activities: marital status, number of children, number of close relatives, number of friends, frequency of attendance at religious services, attendance at organized group meetings, in-degree centrality, out-degree centrality, closeness centrality, and betweenness centrality. Multivariate regression analysis was conducted to examine associations between the identified social network types and self-rated health and depression. The model-based clustering analysis revealed that social networks clustered into five types: diverse, family, congregant, congregant-restricted, and restricted. Diverse or family social network types were significantly associated with more favorable subjective mental health, whereas the restricted network type was significantly associated with poorer ratings of mental and physical health. In addition, our analysis identified unique social network types related to religious activities. In summary, we developed a comprehensive social network typology for older Korean adults. Copyright © 2016 Elsevier Ltd. All rights reserved.

Occupation and malignant lymphoma: a population based case control study in Germany

PubMed Central

Mester, B; Nieters, A; Deeg, E; Elsner, G; Becker, N; Seidler, A

2006-01-01

Aims To identify occupations suspected to be associated with malignant lymphoma and to generate new hypotheses about occupational risks in a multicentre, population based case control study. Methods Male and female patients with malignant lymphoma (n = 710) aged 18–80 years of age were prospectively recruited in six study regions in Germany. For each newly recruited lymphoma case, a sex, region, and age matched control was drawn from the population registers. Odds ratios and 95% confidence intervals for major occupations and industries were calculated using conditional logistic regression analysis, adjusted for smoking (in pack‐years) and alcohol consumption. Patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression analysis. Results The following economic/industrial sectors were positively associated with lymphoma: food products, beverages, tobacco; paper products, publishing and printing; and metals. Chemicals; real estate, renting, and business activities were negatively associated with lymphoma diagnosis. The authors observed an increased overall lymphoma risk among architects; maids; farmers; glass formers; and construction workers. Shoemaking and leather goods making was negatively associated with the lymphoma diagnosis (although based on small numbers). In the occupational group analysis of lymphoma subentities, Hodgkin's lymphoma was significantly associated only with rubber and plastic products making; diffuse large B cell lymphoma risk was considerably increased among metal processors; follicular lymphoma showed highly significant risk increases for several occupational groups (medical, dental, and veterinary workers; sales workers; machinery fitters; and electrical fitters); and multiple myeloma showed a particularly pronounced risk increase for farmers as well as for agriculture and animal husbandry workers. Conclusions The results partly confirm previously defined occupational risks. Occupational risk factors for follicular lymphomas might differ from the overall risk factors for malignant lymphoma. PMID:16361401

The Impact of Adjuvant Postoperative Radiation Therapy and Chemotherapy on Survival After Esophagectomy for Esophageal Carcinoma.

PubMed

Wong, Andrew T; Shao, Meng; Rineer, Justin; Lee, Anna; Schwartz, David; Schreiber, David

2017-06-01

The objective of this study was to analyze the impact on overall survival (OS) from the addition of postoperative radiation with or without chemotherapy after esophagectomy, using a large, hospital-based dataset. Previous retrospective studies have suggested an OS advantage for postoperative chemoradiation over surgery alone, although prospective data are lacking. The National Cancer Data Base was queried to select patients diagnosed with stage pT3-4Nx-0M0 or pT1-4N1-3M0 esophageal carcinoma (squamous cell or adenocarcinoma) from 1998 to 2011 treated with definitive esophagectomy ± postoperative radiation and/or chemotherapy. OS was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was used to identify covariates associated with OS. There were 4893 patients selected, of whom 1153 (23.6%) received postoperative radiation. Most patients receiving radiation also received sequential/concomitant chemotherapy (89.9%). For the entire cohort, postoperative radiation was associated with a statistically significant but modest absolute improvement in survival (hazard ratio 0.77; 95% CI, 0.71-0.83; P < 0.001). On subgroup analysis, postoperative radiation was associated with improved OS for patients with node-positive disease (3-yr OS 34.3 % vs 27.8%, P < 0.001) or positive margins (3-yr OS 36.4% vs 18.0%, P < 0.001). When chemotherapy usage was incorporated, sequential chemotherapy was associated with the best survival (P < 0.001). Multivariate analysis revealed that the addition of chemotherapy to radiation therapy, whether sequentially or concurrently, was a strong prognostic factor for OS. In this hospital-based study, the addition of postoperative chemoradiation (either sequentially or concomitantly) after esophagectomy was associated with improved OS for patients with node-positive disease or positive margins.

Sexting Leads to "Risky" Sex? An Analysis of Sexting Behaviors in a Nonuniversity-Based, Older Adult Population.

PubMed

Currin, Joseph M; Hubach, Randolph D; Sanders, Carissa; Hammer, Tonya R

2017-10-03

Since few researchers have analyzed sexting behaviors in nonuniversity-based adult samples, we sought to determine if sexting is associated with negative psychological correlates and risky sexual behaviors in this population. Analysis of individuals who indicated having vaginal or anal sex in the past 12 months and who identified as single (n = 377) showed that condomless sex is independent of sexting behaviors. Results for those in committed relationships (n = 374) and having had vaginal or anal sex in the past 12 months also demonstrated condomless sex and sexting behaviors were not related. Furthermore, alcohol consumption and relational health were predictive of sexting behaviors in adults in committed relationships. These findings demonstrate that while risky sexual behavior and negative psychological correlates are associated with sexting and younger populations, the same might not be true for a nonuniversity-based, older adult sample.

Associations of job demands and intelligence with cognitive performance among men in late life.

PubMed

Potter, Guy G; Helms, Michael J; Plassman, Brenda L

2008-05-06

To examine the association of job characteristics and intelligence to cognitive status in members of the National Academy of Sciences-National Research Council Twins Registry of World War II veterans. Participants (n = 1,036) included individuals with an assessment of intelligence based on Armed Services testing in early adulthood. In late adulthood, these individuals completed the modified Telephone Interview for Cognitive Status (TICS-m) and occupational history as part of an epidemiologic study of aging and dementia. Occupational history was coded to produce a matrix of job characteristics. Based on factor analysis, job characteristics were interpreted as reflecting general intellectual demands (GI), human interaction and communication (HC), physical activity (PA), and visual attention (VA). Based on regression analysis of TICS-m score covarying for age, intelligence, and years of education, higher levels of GI and HC were independently associated with higher TICS-m performance, whereas higher PA was independently associated with lower performance. There was an interaction of GI and intelligence, indicating that individuals at the lower range of intellectual aptitude in early adulthood derived greater cognitive benefit from intellectually demanding work. Intellectually demanding work was associated with greater benefit to cognitive performance in later life independent of related factors like education and intelligence. The fact that individuals with lower intellectual aptitude demonstrated a stronger positive association between work and higher cognitive performance during retirement suggests that behavior may enhance intellectual reserve, perhaps even years after peak intellectual activity.

Associations of job demands and intelligence with cognitive performance among men in late life

PubMed Central

Potter, Guy G.; Helms, Michael J.; Plassman, Brenda L.

2013-01-01

Objective To examine the association of job characteristics and intelligence to cognitive status in members of the National Academy of Sciences–National Research Council Twins Registry of World War II veterans. Methods Participants (n = 1,036) included individuals with an assessment of intelligence based on Armed Services testing in early adulthood. In late adulthood, these individuals completed the modified Telephone Interview for Cognitive Status (TICS-m) and occupational history as part of an epidemiologic study of aging and dementia. Occupational history was coded to produce a matrix of job characteristics. Based on factor analysis, job characteristics were interpreted as reflecting general intellectual demands (GI), human interaction and communication (HC), physical activity (PA), and visual attention (VA). Results Based on regression analysis of TICS-m score covarying for age, intelligence, and years of education, higher levels of GI and HC were independently associated with higher TICS-m performance, whereas higher PA was independently associated with lower performance. There was an interaction of GI and intelligence, indicating that individuals at the lower range of intellectual aptitude in early adulthood derived greater cognitive benefit from intellectually demanding work. Conclusions Intellectually demanding work was associated with greater benefit to cognitive performance in later life independent of related factors like education and intelligence. The fact that individuals with lower intellectual aptitude demonstrated a stronger positive association between work and higher cognitive performance during retirement suggests that behavior may enhance intellectual reserve, perhaps even years after peak intellectual activity. PMID:18077796

Location and organizational features: what type of veteran communities participate in health programs?

PubMed

Patterson, Leslie; McGinley, Emily; Ertl, Kristyn; Morzinski, Jeffrey; Fyfe, Robert; Whittle, Jeff

2012-01-01

Research shows that community-based membership organizations are effective partners in health promotion activities; however, most community organizations do not participate in such partnerships. There is little research regarding the geographical and organizational characteristics associated with participation. We examined the factors associated with community-based veterans service organization (VSO) units' decision to participate in a health promotion project. We collected location and organizational characteristics regarding 218 VSO units asked to participate in POWER, a partnership to improve hypertension self-management skills between the Medical College of Wisconsin, the Milwaukee Veterans Affairs Medical Center (VAMC) and Wisconsin branches of the American Legion, Veterans of Foreign Wars (VFW), Vietnam Veterans of America, and National Association of Black Veterans. We tested the association of these characteristics with participation using chi-square and Fisher's exact tests for categorical variables, and analysis of variance and the Kruskal-Wallis test for continuous variables. We used multivariable logistic regression to identify factors independently associated with participation. In bivariable analyses, likelihood of participation was positively associated with increasing membership (p < .001), meeting attendance (p < .001), publication of an organizational newsletter (p < .001), presence of a women's auxiliary (p = .02), and location within 44 miles of the VAMC (p = .047). On multivariable analysis, only meeting attendance and census tract-level educational attainment predicted participation. Greater membership sizes, meeting attendance, and more group resources might be important factors for researchers to consider when initiating community-based health and wellness programs.

Gene-Based Association Analysis for Censored Traits Via Fixed Effect Functional Regressions.

PubMed

Fan, Ruzong; Wang, Yifan; Yan, Qi; Ding, Ying; Weeks, Daniel E; Lu, Zhaohui; Ren, Haobo; Cook, Richard J; Xiong, Momiao; Swaroop, Anand; Chew, Emily Y; Chen, Wei

2016-02-01

Genetic studies of survival outcomes have been proposed and conducted recently, but statistical methods for identifying genetic variants that affect disease progression are rarely developed. Motivated by our ongoing real studies, here we develop Cox proportional hazard models using functional regression (FR) to perform gene-based association analysis of survival traits while adjusting for covariates. The proposed Cox models are fixed effect models where the genetic effects of multiple genetic variants are assumed to be fixed. We introduce likelihood ratio test (LRT) statistics to test for associations between the survival traits and multiple genetic variants in a genetic region. Extensive simulation studies demonstrate that the proposed Cox RF LRT statistics have well-controlled type I error rates. To evaluate power, we compare the Cox FR LRT with the previously developed burden test (BT) in a Cox model and sequence kernel association test (SKAT), which is based on mixed effect Cox models. The Cox FR LRT statistics have higher power than or similar power as Cox SKAT LRT except when 50%/50% causal variants had negative/positive effects and all causal variants are rare. In addition, the Cox FR LRT statistics have higher power than Cox BT LRT. The models and related test statistics can be useful in the whole genome and whole exome association studies. An age-related macular degeneration dataset was analyzed as an example. © 2016 WILEY PERIODICALS, INC.

Factors associated with quality of life in active childhood epilepsy: a population-based study.

PubMed

Reilly, Colin; Atkinson, Patricia; Das, Krishna B; Chin, Richard F M; Aylett, Sarah E; Burch, Victoria; Gillberg, Christopher; Scott, Rod C; Neville, Brian G R

2015-05-01

Improving health-related quality of life (HRQOL), rather than just reducing seizures, should be the principal goal in comprehensive management of childhood epilepsy. There is a lack of population-based data on predictors of HRQOL in childhood epilepsy. The Children with Epilepsy in Sussex Schools (CHESS) study is a prospective, population-based study involving school-aged children (5-15 years) with active epilepsy (on one or more AED and/or had a seizure in the last year) in a defined geographical area in the UK. Eighty-five of 115 (74% of eligible population) children underwent comprehensive psychological assessment including measures of cognition, behaviour, and motor functioning. Parents of the children completed the Quality of Life in Childhood Epilepsy (QOLCE).Clinical data on eligible children was extracted using a standardised pro forma. Linear regression analysis was undertaken to identify factors significantly associated with total Quality of Life in this population. Factors independently significantly associated (p < .05) with total QOLCE scores were seizures before 24 months, cognitive impairment (IQ < 85), anxiety, and parent reported school attendance difficulty. These factors were also significantly associated with total QOLCE when children with IQ < 50 were excluded from analysis. The majority of factors associated with parent reported HRQOL in active childhood epilepsy are related to neurobehavioural and/or psychosocial aspects of the condition. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Gene-based Association Analysis for Censored Traits Via Fixed Effect Functional Regressions

PubMed Central

Fan, Ruzong; Wang, Yifan; Yan, Qi; Ding, Ying; Weeks, Daniel E.; Lu, Zhaohui; Ren, Haobo; Cook, Richard J; Xiong, Momiao; Swaroop, Anand; Chew, Emily Y.; Chen, Wei

2015-01-01

Summary Genetic studies of survival outcomes have been proposed and conducted recently, but statistical methods for identifying genetic variants that affect disease progression are rarely developed. Motivated by our ongoing real studies, we develop here Cox proportional hazard models using functional regression (FR) to perform gene-based association analysis of survival traits while adjusting for covariates. The proposed Cox models are fixed effect models where the genetic effects of multiple genetic variants are assumed to be fixed. We introduce likelihood ratio test (LRT) statistics to test for associations between the survival traits and multiple genetic variants in a genetic region. Extensive simulation studies demonstrate that the proposed Cox RF LRT statistics have well-controlled type I error rates. To evaluate power, we compare the Cox FR LRT with the previously developed burden test (BT) in a Cox model and sequence kernel association test (SKAT) which is based on mixed effect Cox models. The Cox FR LRT statistics have higher power than or similar power as Cox SKAT LRT except when 50%/50% causal variants had negative/positive effects and all causal variants are rare. In addition, the Cox FR LRT statistics have higher power than Cox BT LRT. The models and related test statistics can be useful in the whole genome and whole exome association studies. An age-related macular degeneration dataset was analyzed as an example. PMID:26782979

Association mapping unveils favorable alleles for grain iron and zinc concentrations in lentil (Lens culinaris subsp. culinaris)

PubMed Central

Singh, Akanksha; Sharma, Vinay; Dikshit, Harsh Kumar; Aski, Muraleedhar; Kumar, Harish; Thirunavukkarasu, Nepolean; Patil, Basavanagouda S.; Kumar, Shiv; Sarker, Ashutosh

2017-01-01

Lentil is a major cool-season grain legume grown in South Asia, West Asia, and North Africa. Populations in developing countries of these regions have micronutrient deficiencies; therefore, breeding programs should focus more on improving the micronutrient content of food. In the present study, a set of 96 diverse germplasm lines were evaluated at three different locations in India to examine the variation in iron (Fe) and zinc (Zn) concentration and identify simple sequence repeat (SSR) markers that associate with the genetic variation. The genetic variation among genotypes of the association mapping (AM) panel was characterized using a genetic distance-based and a general model-based clustering method. The model-based analysis identified six subpopulations, which satisfactorily explained the genetic structure of the AM panel. AM analysis identified three SSRs (PBALC 13, PBALC 206, and GLLC 563) associated with grain Fe concentration explaining 9% to 11% of phenotypic variation and four SSRs (PBALC 353, SSR 317–1, PLC 62, and PBALC 217) were associated with grain Zn concentration explaining 14%, to 21% of phenotypic variation. These identified SSRs exhibited consistent performance across locations. These candidate SSRs can be used in marker-assisted genetic improvement for developing Fe and Zn fortified lentil varieties. Favorable alleles and promising genotypes identified in this study can be utilized for lentil biofortification. PMID:29161321

Digital microarray analysis for digital artifact genomics

NASA Astrophysics Data System (ADS)

Jaenisch, Holger; Handley, James; Williams, Deborah

2013-06-01

We implement a Spatial Voting (SV) based analogy of microarray analysis for digital gene marker identification in malware code sections. We examine a famous set of malware formally analyzed by Mandiant and code named Advanced Persistent Threat (APT1). APT1 is a Chinese organization formed with specific intent to infiltrate and exploit US resources. Manidant provided a detailed behavior and sting analysis report for the 288 malware samples available. We performed an independent analysis using a new alternative to the traditional dynamic analysis and static analysis we call Spatial Analysis (SA). We perform unsupervised SA on the APT1 originating malware code sections and report our findings. We also show the results of SA performed on some members of the families associated by Manidant. We conclude that SV based SA is a practical fast alternative to dynamics analysis and static analysis.

Testing Genetic Pleiotropy with GWAS Summary Statistics for Marginal and Conditional Analyses.

PubMed

Deng, Yangqing; Pan, Wei

2017-12-01

There is growing interest in testing genetic pleiotropy, which is when a single genetic variant influences multiple traits. Several methods have been proposed; however, these methods have some limitations. First, all the proposed methods are based on the use of individual-level genotype and phenotype data; in contrast, for logistical, and other, reasons, summary statistics of univariate SNP-trait associations are typically only available based on meta- or mega-analyzed large genome-wide association study (GWAS) data. Second, existing tests are based on marginal pleiotropy, which cannot distinguish between direct and indirect associations of a single genetic variant with multiple traits due to correlations among the traits. Hence, it is useful to consider conditional analysis, in which a subset of traits is adjusted for another subset of traits. For example, in spite of substantial lowering of low-density lipoprotein cholesterol (LDL) with statin therapy, some patients still maintain high residual cardiovascular risk, and, for these patients, it might be helpful to reduce their triglyceride (TG) level. For this purpose, in order to identify new therapeutic targets, it would be useful to identify genetic variants with pleiotropic effects on LDL and TG after adjusting the latter for LDL; otherwise, a pleiotropic effect of a genetic variant detected by a marginal model could simply be due to its association with LDL only, given the well-known correlation between the two types of lipids. Here, we develop a new pleiotropy testing procedure based only on GWAS summary statistics that can be applied for both marginal analysis and conditional analysis. Although the main technical development is based on published union-intersection testing methods, care is needed in specifying conditional models to avoid invalid statistical estimation and inference. In addition to the previously used likelihood ratio test, we also propose using generalized estimating equations under the working independence model for robust inference. We provide numerical examples based on both simulated and real data, including two large lipid GWAS summary association datasets based on ∼100,000 and ∼189,000 samples, respectively, to demonstrate the difference between marginal and conditional analyses, as well as the effectiveness of our new approach. Copyright © 2017 by the Genetics Society of America.

Gene duplications in prokaryotes can be associated with environmental adaptation

PubMed Central

2010-01-01

Background Gene duplication is a normal evolutionary process. If there is no selective advantage in keeping the duplicated gene, it is usually reduced to a pseudogene and disappears from the genome. However, some paralogs are retained. These gene products are likely to be beneficial to the organism, e.g. in adaptation to new environmental conditions. The aim of our analysis is to investigate the properties of paralog-forming genes in prokaryotes, and to analyse the role of these retained paralogs by relating gene properties to life style of the corresponding prokaryotes. Results Paralogs were identified in a number of prokaryotes, and these paralogs were compared to singletons of persistent orthologs based on functional classification. This showed that the paralogs were associated with for example energy production, cell motility, ion transport, and defence mechanisms. A statistical overrepresentation analysis of gene and protein annotations was based on paralogs of the 200 prokaryotes with the highest fraction of paralog-forming genes. Biclustering of overrepresented gene ontology terms versus species was used to identify clusters of properties associated with clusters of species. The clusters were classified using similarity scores on properties and species to identify interesting clusters, and a subset of clusters were analysed by comparison to literature data. This analysis showed that paralogs often are associated with properties that are important for survival and proliferation of the specific organisms. This includes processes like ion transport, locomotion, chemotaxis and photosynthesis. However, the analysis also showed that the gene ontology terms sometimes were too general, imprecise or even misleading for automatic analysis. Conclusions Properties described by gene ontology terms identified in the overrepresentation analysis are often consistent with individual prokaryote lifestyles and are likely to give a competitive advantage to the organism. Paralogs and singletons dominate different categories of functional classification, where paralogs in particular seem to be associated with processes involving interaction with the environment. PMID:20961426

Gene duplications in prokaryotes can be associated with environmental adaptation.

PubMed

Bratlie, Marit S; Johansen, Jostein; Sherman, Brad T; Huang, Da Wei; Lempicki, Richard A; Drabløs, Finn

2010-10-20

Gene duplication is a normal evolutionary process. If there is no selective advantage in keeping the duplicated gene, it is usually reduced to a pseudogene and disappears from the genome. However, some paralogs are retained. These gene products are likely to be beneficial to the organism, e.g. in adaptation to new environmental conditions. The aim of our analysis is to investigate the properties of paralog-forming genes in prokaryotes, and to analyse the role of these retained paralogs by relating gene properties to life style of the corresponding prokaryotes. Paralogs were identified in a number of prokaryotes, and these paralogs were compared to singletons of persistent orthologs based on functional classification. This showed that the paralogs were associated with for example energy production, cell motility, ion transport, and defence mechanisms. A statistical overrepresentation analysis of gene and protein annotations was based on paralogs of the 200 prokaryotes with the highest fraction of paralog-forming genes. Biclustering of overrepresented gene ontology terms versus species was used to identify clusters of properties associated with clusters of species. The clusters were classified using similarity scores on properties and species to identify interesting clusters, and a subset of clusters were analysed by comparison to literature data. This analysis showed that paralogs often are associated with properties that are important for survival and proliferation of the specific organisms. This includes processes like ion transport, locomotion, chemotaxis and photosynthesis. However, the analysis also showed that the gene ontology terms sometimes were too general, imprecise or even misleading for automatic analysis. Properties described by gene ontology terms identified in the overrepresentation analysis are often consistent with individual prokaryote lifestyles and are likely to give a competitive advantage to the organism. Paralogs and singletons dominate different categories of functional classification, where paralogs in particular seem to be associated with processes involving interaction with the environment.

PHYLOViZ: phylogenetic inference and data visualization for sequence based typing methods

PubMed Central

2012-01-01

Background With the decrease of DNA sequencing costs, sequence-based typing methods are rapidly becoming the gold standard for epidemiological surveillance. These methods provide reproducible and comparable results needed for a global scale bacterial population analysis, while retaining their usefulness for local epidemiological surveys. Online databases that collect the generated allelic profiles and associated epidemiological data are available but this wealth of data remains underused and are frequently poorly annotated since no user-friendly tool exists to analyze and explore it. Results PHYLOViZ is platform independent Java software that allows the integrated analysis of sequence-based typing methods, including SNP data generated from whole genome sequence approaches, and associated epidemiological data. goeBURST and its Minimum Spanning Tree expansion are used for visualizing the possible evolutionary relationships between isolates. The results can be displayed as an annotated graph overlaying the query results of any other epidemiological data available. Conclusions PHYLOViZ is a user-friendly software that allows the combined analysis of multiple data sources for microbial epidemiological and population studies. It is freely available at http://www.phyloviz.net. PMID:22568821

Space transportation architecture: Reliability sensitivities

NASA Technical Reports Server (NTRS)

Williams, A. M.

1992-01-01

A sensitivity analysis is given of the benefits and drawbacks associated with a proposed Earth to orbit vehicle architecture. The architecture represents a fleet of six vehicles (two existing, four proposed) that would be responsible for performing various missions as mandated by NASA and the U.S. Air Force. Each vehicle has a prescribed flight rate per year for a period of 31 years. By exposing this fleet of vehicles to a probabilistic environment where the fleet experiences failures, downtimes, setbacks, etc., the analysis involves determining the resiliency and costs associated with the fleet of specific vehicle/subsystem reliabilities. The resources required were actual observed data on the failures and downtimes associated with existing vehicles, data based on engineering judgement for proposed vehicles, and the development of a sensitivity analysis program.

[Study of post marketing safety reevaluation of shenqi fuzheng injection].

PubMed

Ai, Qing-Hua; Li, Yuan-Yuan; Xie, Yan-Ming

2014-09-01

In order to promote the Shenqifuzheng injection (SQFZ) clinical medication safety, this study reevaluate on SQFZ post marketing safety study systematically. Including multi center large sample registration type safety monitoring research, the analysis based on national spontaneous reporting system data, the analysis based on the 20 national hospital information system data and literature research. Above the analysis, it suggests that SQFZ has good security. The more adverse drug reaction (ADR) as allergic reactions, mainly involved in the damage of skin, appendages and its systemic damage, serious person can appear allergic shock. ADR/E is more common in the elderly, may be related to medication (tumor) populations. Early warning analysis based on SRS data and literature research are of the view that "phlebitis" has a strong association with SQFZ used.

Raft cultivation area extraction from high resolution remote sensing imagery by fusing multi-scale region-line primitive association features

NASA Astrophysics Data System (ADS)

Wang, Min; Cui, Qi; Wang, Jie; Ming, Dongping; Lv, Guonian

2017-01-01

In this paper, we first propose several novel concepts for object-based image analysis, which include line-based shape regularity, line density, and scale-based best feature value (SBV), based on the region-line primitive association framework (RLPAF). We then propose a raft cultivation area (RCA) extraction method for high spatial resolution (HSR) remote sensing imagery based on multi-scale feature fusion and spatial rule induction. The proposed method includes the following steps: (1) Multi-scale region primitives (segments) are obtained by image segmentation method HBC-SEG, and line primitives (straight lines) are obtained by phase-based line detection method. (2) Association relationships between regions and lines are built based on RLPAF, and then multi-scale RLPAF features are extracted and SBVs are selected. (3) Several spatial rules are designed to extract RCAs within sea waters after land and water separation. Experiments show that the proposed method can successfully extract different-shaped RCAs from HR images with good performance.

A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson's disease

PubMed Central

Holmans, Peter; Moskvina, Valentina; Jones, Lesley; Sharma, Manu; Vedernikov, Alexey; Buchel, Finja; Sadd, Mohamad; Bras, Jose M.; Bettella, Francesco; Nicolaou, Nayia; Simón-Sánchez, Javier; Mittag, Florian; Gibbs, J. Raphael; Schulte, Claudia; Durr, Alexandra; Guerreiro, Rita; Hernandez, Dena; Brice, Alexis; Stefánsson, Hreinn; Majamaa, Kari; Gasser, Thomas; Heutink, Peter; Wood, Nicholas W.; Martinez, Maria; Singleton, Andrew B.; Nalls, Michael A.; Hardy, John; Morris, Huw R.; Williams, Nigel M.; Arepalli, Sampath; Barker, Roger; Barrett, Jeffrey; Ben-Shlomo, Yoav; Berendse, Henk W.; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M.A.; Biffi, Alessandro; Bloem, Bas; Brice, Alexis; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Cooper, Jonathan M.; Corvol, Jen-Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean Francois; Deloukas, Panagiotis; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Durif, Frank; Durr, Alexandra; Edkins, Sarah; Evans, Jonathan R.; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Gasser, Thomas; Gibbs, J. Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Gústafsson, Ómar; Hardy, John; Harris, Clare; Hernandez, Dena G.; Heutink, Peter; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holmans, Peter; Holton, Janice; Hu, Michele; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Langford, Cordelia; Lees, Andrew; Lesage, Suzanne; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; Martinez, Maria; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw; Morrison, Karen E.; Moskvina, Valentina; Mudanohwo, Ese; Nalls, Michael A.; Pearson, Justin; Perlmutter, Joel S.; Pétursson, Hjörvar; Plagnol, Vincent; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Saad, Mohamad; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Sharma, Manu; Shaw, Karen; Sheerin, Una-Marie; Shoulson, Ira; Schulte, Claudia; Sidransky, Ellen; Simón-Sánchez, Javier; Singleton, Andrew B.; Smith, Colin; Stefánsson, Hreinn; Stefánsson, Kári; Steinberg, Stacy; Stockton, Joanna D.; Sveinbjornsdottir, Sigurlaug; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Wood, Nicholas

2013-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 1–2% in people >60 and 3–4% in people >80. Genome-wide association (GWA) studies have now implicated significant evidence for association in at least 18 genomic regions. We have studied a large PD-meta analysis and identified a significant excess of SNPs (P < 1 × 10−16) that are associated with PD but fall short of the genome-wide significance threshold. This result was independent of variants at the 18 previously implicated regions and implies the presence of additional polygenic risk alleles. To understand how these loci increase risk of PD, we applied a pathway-based analysis, testing for biological functions that were significantly enriched for genes containing variants associated with PD. Analysing two independent GWA studies, we identified that both had a significant excess in the number of functional categories enriched for PD-associated genes (minimum P = 0.014 and P = 0.006, respectively). Moreover, 58 categories were significantly enriched for associated genes in both GWA studies (P < 0.001), implicating genes involved in the ‘regulation of leucocyte/lymphocyte activity’ and also ‘cytokine-mediated signalling’ as conferring an increased susceptibility to PD. These results were unaltered by the exclusion of all 178 genes that were present at the 18 genomic regions previously reported to be strongly associated with PD (including the HLA locus). Our findings, therefore, provide independent support to the strong association signal at the HLA locus and imply that the immune-related genetic susceptibility to PD is likely to be more widespread in the genome than previously appreciated. PMID:23223016

Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk.

PubMed

Kar, Siddhartha P; Tyrer, Jonathan P; Li, Qiyuan; Lawrenson, Kate; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Chenevix-Trench, Georgia; Baker, Helen; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Berchuck, Andrew; Bisogna, Maria; Bjørge, Line; Bogdanova, Natalia; Brinton, Louise; Brooks-Wilson, Angela; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Chen, Yian Ann; Chen, Zhihua; Cook, Linda S; Cramer, Daniel; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas F; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus K; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Paul, James; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kjaer, Susanne K; Kelemen, Linda E; Kellar, Melissa; Kelley, Joseph; Kiemeney, Lambertus A; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Iain A; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B; Narod, Steven A; Nedergaard, Lotte; Ness, Roberta B; Nevanlinna, Heli; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Phelan, Catherine M; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schildkraut, Joellen M; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Sucheston-Campbell, Lara E; Tangen, Ingvild L; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S; van Altena, Anne M; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A; Monteiro, Alvaro N A; Freedman, Matthew L; Gayther, Simon A; Pharoah, Paul D P

2015-10-01

Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations. We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. ©2015 American Association for Cancer Research.

Advanced Connectivity Analysis (ACA): a Large Scale Functional Connectivity Data Mining Environment.

PubMed

Chen, Rong; Nixon, Erika; Herskovits, Edward

2016-04-01

Using resting-state functional magnetic resonance imaging (rs-fMRI) to study functional connectivity is of great importance to understand normal development and function as well as a host of neurological and psychiatric disorders. Seed-based analysis is one of the most widely used rs-fMRI analysis methods. Here we describe a freely available large scale functional connectivity data mining software package called Advanced Connectivity Analysis (ACA). ACA enables large-scale seed-based analysis and brain-behavior analysis. It can seamlessly examine a large number of seed regions with minimal user input. ACA has a brain-behavior analysis component to delineate associations among imaging biomarkers and one or more behavioral variables. We demonstrate applications of ACA to rs-fMRI data sets from a study of autism.

Sequential sentinel SNP Regional Association Plots (SSS-RAP): an approach for testing independence of SNP association signals using meta-analysis data.

PubMed

Zheng, Jie; Gaunt, Tom R; Day, Ian N M

2013-01-01

Genome-Wide Association Studies (GWAS) frequently incorporate meta-analysis within their framework. However, conditional analysis of individual-level data, which is an established approach for fine mapping of causal sites, is often precluded where only group-level summary data are available for analysis. Here, we present a numerical and graphical approach, "sequential sentinel SNP regional association plot" (SSS-RAP), which estimates regression coefficients (beta) with their standard errors using the meta-analysis summary results directly. Under an additive model, typical for genes with small effect, the effect for a sentinel SNP can be transformed to the predicted effect for a possibly dependent SNP through a 2×2 2-SNP haplotypes table. The approach assumes Hardy-Weinberg equilibrium for test SNPs. SSS-RAP is available as a Web-tool (http://apps.biocompute.org.uk/sssrap/sssrap.cgi). To develop and illustrate SSS-RAP we analyzed lipid and ECG traits data from the British Women's Heart and Health Study (BWHHS), evaluated a meta-analysis for ECG trait and presented several simulations. We compared results with existing approaches such as model selection methods and conditional analysis. Generally findings were consistent. SSS-RAP represents a tool for testing independence of SNP association signals using meta-analysis data, and is also a convenient approach based on biological principles for fine mapping in group level summary data. © 2012 Blackwell Publishing Ltd/University College London.

Integrating genome-wide association study and expression quantitative trait loci data identifies multiple genes and gene set associated with neuroticism.

PubMed

Fan, Qianrui; Wang, Wenyu; Hao, Jingcan; He, Awen; Wen, Yan; Guo, Xiong; Wu, Cuiyan; Ning, Yujie; Wang, Xi; Wang, Sen; Zhang, Feng

2017-08-01

Neuroticism is a fundamental personality trait with significant genetic determinant. To identify novel susceptibility genes for neuroticism, we conducted an integrative analysis of genomic and transcriptomic data of genome wide association study (GWAS) and expression quantitative trait locus (eQTL) study. GWAS summary data was driven from published studies of neuroticism, totally involving 170,906 subjects. eQTL dataset containing 927,753 eQTLs were obtained from an eQTL meta-analysis of 5311 samples. Integrative analysis of GWAS and eQTL data was conducted by summary data-based Mendelian randomization (SMR) analysis software. To identify neuroticism associated gene sets, the SMR analysis results were further subjected to gene set enrichment analysis (GSEA). The gene set annotation dataset (containing 13,311 annotated gene sets) of GSEA Molecular Signatures Database was used. SMR single gene analysis identified 6 significant genes for neuroticism, including MSRA (p value=2.27×10 -10 ), MGC57346 (p value=6.92×10 -7 ), BLK (p value=1.01×10 -6 ), XKR6 (p value=1.11×10 -6 ), C17ORF69 (p value=1.12×10 -6 ) and KIAA1267 (p value=4.00×10 -6 ). Gene set enrichment analysis observed significant association for Chr8p23 gene set (false discovery rate=0.033). Our results provide novel clues for the genetic mechanism studies of neuroticism. Copyright © 2017. Published by Elsevier Inc.

Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese.

PubMed

Tang, Clara S; Zhang, He; Cheung, Chloe Y Y; Xu, Ming; Ho, Jenny C Y; Zhou, Wei; Cherny, Stacey S; Zhang, Yan; Holmen, Oddgeir; Au, Ka-Wing; Yu, Haiyi; Xu, Lin; Jia, Jia; Porsch, Robert M; Sun, Lijie; Xu, Weixian; Zheng, Huiping; Wong, Lai-Yung; Mu, Yiming; Dou, Jingtao; Fong, Carol H Y; Wang, Shuyu; Hong, Xueyu; Dong, Liguang; Liao, Yanhua; Wang, Jiansong; Lam, Levina S M; Su, Xi; Yan, Hua; Yang, Min-Lee; Chen, Jin; Siu, Chung-Wah; Xie, Gaoqiang; Woo, Yu-Cho; Wu, Yangfeng; Tan, Kathryn C B; Hveem, Kristian; Cheung, Bernard M Y; Zöllner, Sebastian; Xu, Aimin; Eugene Chen, Y; Jiang, Chao Qiang; Zhang, Youyi; Lam, Tai-Hing; Ganesh, Santhi K; Huo, Yong; Sham, Pak C; Lam, Karen S L; Willer, Cristen J; Tse, Hung-Fat; Gao, Wei

2015-12-22

Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P<2.69 × 10(-7)), including three Asian-specific coding variants in known genes (CETP p.Asp459Gly, PCSK9 p.Arg93Cys and LDLR p.Arg257Trp). Furthermore, missense variants at two novel loci-PNPLA3 p.Ile148Met and PKD1L3 p.Thr429Ser-also influence levels of triglycerides and low-density lipoprotein cholesterol, respectively. Another novel gene, TEAD2, is found to be associated with high-density lipoprotein cholesterol through gene-based association analysis. Most of these newly identified coding variants show suggestive association (P<0.05) with CAD. These findings demonstrate that exome-wide genotyping on samples of non-European ancestry can identify additional population-specific possible causal variants, shedding light on novel lipid biology and CAD.

Gender-Based Barriers Experienced by Male Students in an Online RN-to-BSN Nursing Program

ERIC Educational Resources Information Center

Kirk, John R.

2012-01-01

This quantitative survey-based research study examined the experiences of 49 men through a comparative analysis of their traditional classroom-based Diploma or Associate Degree in Nursing program and their subsequent experiences in the University of Phoenix online Registered Nurse to Bachelor of Science in Nursing (RN-to-BSN) degree completion…

Rumours about wildlife pest introductions: European rabbits in Spain.

PubMed

Delibes-Mateos, Miguel

2017-03-01

Rumours associated with wildlife are frequent, although they have received little attention in the scientific literature. Studying rumours is important because of their relevance not only in a broad theoretical sense but also in environmental management. The goal of this study is to explore the complexity of the relationships between humans and wildlife through a thematic analysis of rumours associated with allegedly introduced European rabbits (Oryctolagus cuniculus) that cause crop damage in Spain. For this purpose, potential rumours were identified using the Google search engine. Data analysis consisted of reading and re-reading Web-based texts to identify main themes, ideas and topics with the assistance of NVivo 10 software. The analysis identified three main themes: (1) the reviewed websites referred to allegedly introduced rabbits which differed from native rabbits; (2) differences were based on alleged observations of unnatural behaviour, physiology or physical appearance of introduced rabbits; (3) rumours were frequently used in the context of the rabbit management conflict; e.g. farmers accused hunters of releasing harmful rabbits. This study suggests that the analysis of wildlife-release rumours sheds light on the position of parties involved in conflicts associated with the (alleged) introduction of wildlife species. It stresses the importance of rumours in conservation and environmental management, and opens the door to future research.

Association between coffee intake and gastroesophageal reflux disease: a meta-analysis.

PubMed

Kim, J; Oh, S-W; Myung, S-K; Kwon, H; Lee, C; Yun, J M; Lee, H K

2014-01-01

Gastroesophageal reflux disease (GERD) is one of the most common diseases affecting patients worldwide, but its risk factors and causes are not clearly known. The aim of this study was to investigate the effect of coffee intake on GERD by a meta-analysis. We searched online published research databases such as PubMed, EMBASE, and Cochrane Library for studies that were published up to December 2012. These publications were reviewed by two independent authors, and studies that fulfilled the criteria were selected. Whenever there was a disagreement between the authors, a consensus was reached by discussion. Fifteen case-control studies were included in the final analysis. A meta-analysis showed that there was no significant association between coffee intake and GERD. The odds ratio was 1.06 (95% confidence interval, 0.94-1.19). In subgroup analyses in which the groups were subdivided based on the definition of GERD (diagnosed by endoscopy or by symptoms alone), only the endoscopy group showed a significantly higher odds ratio. In subgroup analyses in which the groups were subdivided based on the amount of coffee intake, quality of study, and assessment of exposure, there was no significant association between coffee intake and GERD. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Model-based engineering for laser weapons systems

NASA Astrophysics Data System (ADS)

Panthaki, Malcolm; Coy, Steve

2011-10-01

The Comet Performance Engineering Workspace is an environment that enables integrated, multidisciplinary modeling and design/simulation process automation. One of the many multi-disciplinary applications of the Comet Workspace is for the integrated Structural, Thermal, Optical Performance (STOP) analysis of complex, multi-disciplinary space systems containing Electro-Optical (EO) sensors such as those which are designed and developed by and for NASA and the Department of Defense. The CometTM software is currently able to integrate performance simulation data and processes from a wide range of 3-D CAD and analysis software programs including CODE VTM from Optical Research Associates and SigFitTM from Sigmadyne Inc. which are used to simulate the optics performance of EO sensor systems in space-borne applications. Over the past year, Comet Solutions has been working with MZA Associates of Albuquerque, NM, under a contract with the Air Force Research Laboratories. This funded effort is a "risk reduction effort", to help determine whether the combination of Comet and WaveTrainTM, a wave optics systems engineering analysis environment developed and maintained by MZA Associates and used by the Air Force Research Laboratory, will result in an effective Model-Based Engineering (MBE) environment for the analysis and design of laser weapons systems. This paper will review the results of this effort and future steps.

Chromosome evolution in the Thermotogales: large-scale inversions and strain diversification of CRISPR sequences.

PubMed

DeBoy, Robert T; Mongodin, Emmanuel F; Emerson, Joanne B; Nelson, Karen E

2006-04-01

In the present study, the chromosomes of two members of the Thermotogales were compared. A whole-genome alignment of Thermotoga maritima MSB8 and Thermotoga neapolitana NS-E has revealed numerous large-scale DNA rearrangements, most of which are associated with CRISPR DNA repeats and/or tRNA genes. These DNA rearrangements do not include the putative origin of DNA replication but move within the same replichore, i.e., the same replicating half of the chromosome (delimited by the replication origin and terminus). Based on cumulative GC skew analysis, both the T. maritima and T. neapolitana lineages contain one or two major inverted DNA segments. Also, based on PCR amplification and sequence analysis of the DNA joints that are associated with the major rearrangements, the overall chromosome architecture was found to be conserved at most DNA joints for other strains of T. neapolitana. Taken together, the results from this analysis suggest that the observed chromosomal rearrangements in the Thermotogales likely occurred by successive inversions after their divergence from a common ancestor and before strain diversification. Finally, sequence analysis shows that size polymorphisms in the DNA joints associated with CRISPRs can be explained by expansion and possibly contraction of the DNA repeat and spacer unit, providing a tool for discerning the relatedness of strains from different geographic locations.

Using landslide risk analysis to protect fish habitat

Treesearch

R. M. Rice

1986-01-01

The protection of anadromous fish habitat is an important water quslity concern in the Pacific Northwest. Sediment from logging-related debris avalanches can cause habitat degradation. Research on conditions associated with the sites where debris avalanches originate has resulted in a risk assessment methodology based on linear discriminant analysis. The probability...

Dispositional Variables and Work-Family Conflict: A Meta-Analysis

ERIC Educational Resources Information Center

Allen, Tammy D.; Johnson, Ryan C.; Saboe, Kristin N.; Cho, Eunae; Dumani, Soner; Evans, Sarah

2012-01-01

Meta-analysis was used to comprehensively summarize the relationship between dispositional variables and both directions of work-family conflict. The largest effects detected were those associated with negative affect, neuroticism, and self-efficacy; all were in expected directions. In general, negative trait-based variables (e.g., negative affect…

HYDROLOGIC MODEL CALIBRATION AND UNCERTAINTY IN SCENARIO ANALYSIS

EPA Science Inventory

A systematic analysis of model performance during simulations based on

observed land-cover/use change is used to quantify error associated with water-yield

simulations for a series of known landscape conditions over a 24-year period with the

goal of evaluatin...

Smoking habits and leukocyte telomere length dynamics among older adults: Results from the ESTHER cohort.

PubMed

Müezzinler, Aysel; Mons, Ute; Dieffenbach, Aida Karina; Butterbach, Katja; Saum, Kai-Uwe; Schick, Matthias; Stammer, Hermann; Boukamp, Petra; Holleczek, Bernd; Stegmaier, Christa; Brenner, Hermann

2015-10-01

Leukocyte telomere length (LTL) shortens with age and short LTL has been associated with increased mortality and increased risk for some age-related outcomes. This study aims to analyse the associations of smoking habits with LTL and rate of LTL change per year in older adults. LTL was measured by quantitative PCR at baseline in 3600 older adults, who were enrolled in a population-based cohort study in Germany. For longitudinal analyses, measurements were repeated in blood samples obtained at 8-year follow-up from 1000 participants. Terminal Restriction Fragment analysis was additionally performed in a sub-sample to obtain absolute LTL in base pairs. Multivariate linear regression models were used to estimate associations of smoking habits with baseline LTL and changes in LTL over time. LTL was inversely associated with age (r=-0.090, p<0.0001). Women had longer LTL than men (p<0.0001). Smoking was inversely associated with LTL. On average, current smokers had 73 base pairs (BP) shorter LTL compared to never smokers. Smoking intensity and pack-years of smoking were also inversely associated with LTL, and a positive association was observed with years since smoking cessation. Slower LTL attrition rates were observed in ever smokers over 8years of follow-up. Our cross-sectional analysis supports suggestions that smoking might contribute to shortening of LTL but this relationship could not be shown longitudinally. The overall rather small effect sizes observed for smoking-related variables suggest that LTL reflects smoking-related health hazards only to a very limited extent. Copyright © 2015 Elsevier Inc. All rights reserved.

Factors Associated With Changes in Body Composition Shortly After Orthotopic Liver Transplantation: The Potential Influence of Immunosuppressive Agents.

PubMed

Brito-Costa, Ana; Pereira-da-Silva, Luís; Papoila, Ana Luísa; Alves, Marta; Mateus, Élia; Nolasco, Fernando; Barroso, Eduardo

2016-08-01

This study aimed to determine factors associated with body composition changes shortly after liver transplantation (LTx), including the influence of immunosuppressive agents. The combined resting energy expenditure (REE) and handgrip strength provided a valuable assessment in data interpretation of body composition. This observational single-center study included a cohort of consecutive end-stage liver disease patients with indications for LTx over 2 years. Cyclosporine was preferred for diabetic, hepatitis C-infected, and human immunodeficiency virus-infected patients per the transplant center protocol. Subjective Global Assessment, handgrip strength, multifrequency bioelectrical impedance analysis, and REE measurements were collected. The assessments were performed before LTx (T0) and at medians of 9 (T1) and 36 (T2) days after LTx. The fat mass index (FMI) and lean mass index (LMI) were surrogates of adiposity and skeletal muscle, respectively. Multiple linear regression analysis was used. Fifty-six patients with a mean age of 53.7 (8.5) years were included; 87.5% were men. Preoperative Subjective Global Assessment undernourishment (β-estimate = 17.9; P = 0.004) and of drug addiction absence (β estimate = 14.6; P = 0.049) were associated with FMI increase. Higher REE at T1 (per 100 kcal) was associated with LMI increase (β estimate = 1.70; P = 0.012) and body cell mass increase (β estimate = 1.60; P = 0.049). The cyclosporine-based regimen was associated with FMI decrease (β estimate = -25.64; P < 0.001) and LMI increase (β estimate = 23.76; P < 0.001) when compared with a tacrolimus-based regimen. Steroids did not affect body composition. The cyclosporine-based regimen was independently associated with decreased adiposity and increased skeletal muscle compared with the tacrolimus-based regimen. Future randomized controlled trials are needed to confirm these findings.

What Constitutes a Phrase in Sound-Based Music? A Mixed-Methods Investigation of Perception and Acoustics.

PubMed

Olsen, Kirk N; Dean, Roger T; Leung, Yvonne

2016-01-01

Phrasing facilitates the organization of auditory information and is central to speech and music. Not surprisingly, aspects of changing intensity, rhythm, and pitch are key determinants of musical phrases and their boundaries in instrumental note-based music. Different kinds of speech (such as tone- vs. stress-languages) share these features in different proportions and form an instructive comparison. However, little is known about whether or how musical phrasing is perceived in sound-based music, where the basic musical unit from which a piece is created is commonly non-instrumental continuous sounds, rather than instrumental discontinuous notes. This issue forms the target of the present paper. Twenty participants (17 untrained in music) were presented with six stimuli derived from sound-based music, note-based music, and environmental sound. Their task was to indicate each occurrence of a perceived phrase and qualitatively describe key characteristics of the stimulus associated with each phrase response. It was hypothesized that sound-based music does elicit phrase perception, and that this is primarily associated with temporal changes in intensity and timbre, rather than rhythm and pitch. Results supported this hypothesis. Qualitative analysis of participant descriptions showed that for sound-based music, the majority of perceived phrases were associated with intensity or timbral change. For the note-based piano piece, rhythm was the main theme associated with perceived musical phrasing. We modeled the occurrence in time of perceived musical phrases with recurrent event 'hazard' analyses using time-series data representing acoustic predictors associated with intensity, spectral flatness, and rhythmic density. Acoustic intensity and timbre (represented here by spectral flatness) were strong predictors of perceived musical phrasing in sound-based music, and rhythm was only predictive for the piano piece. A further analysis including five additional spectral measures linked to timbre strengthened the models. Overall, results show that even when little of the pitch and rhythm information important for phrasing in note-based music is available, phrasing is still perceived, primarily in response to changes of intensity and timbre. Implications for electroacoustic music composition and music recommender systems are discussed.

What Constitutes a Phrase in Sound-Based Music? A Mixed-Methods Investigation of Perception and Acoustics

PubMed Central

Olsen, Kirk N.; Dean, Roger T.; Leung, Yvonne

2016-01-01

Phrasing facilitates the organization of auditory information and is central to speech and music. Not surprisingly, aspects of changing intensity, rhythm, and pitch are key determinants of musical phrases and their boundaries in instrumental note-based music. Different kinds of speech (such as tone- vs. stress-languages) share these features in different proportions and form an instructive comparison. However, little is known about whether or how musical phrasing is perceived in sound-based music, where the basic musical unit from which a piece is created is commonly non-instrumental continuous sounds, rather than instrumental discontinuous notes. This issue forms the target of the present paper. Twenty participants (17 untrained in music) were presented with six stimuli derived from sound-based music, note-based music, and environmental sound. Their task was to indicate each occurrence of a perceived phrase and qualitatively describe key characteristics of the stimulus associated with each phrase response. It was hypothesized that sound-based music does elicit phrase perception, and that this is primarily associated with temporal changes in intensity and timbre, rather than rhythm and pitch. Results supported this hypothesis. Qualitative analysis of participant descriptions showed that for sound-based music, the majority of perceived phrases were associated with intensity or timbral change. For the note-based piano piece, rhythm was the main theme associated with perceived musical phrasing. We modeled the occurrence in time of perceived musical phrases with recurrent event ‘hazard’ analyses using time-series data representing acoustic predictors associated with intensity, spectral flatness, and rhythmic density. Acoustic intensity and timbre (represented here by spectral flatness) were strong predictors of perceived musical phrasing in sound-based music, and rhythm was only predictive for the piano piece. A further analysis including five additional spectral measures linked to timbre strengthened the models. Overall, results show that even when little of the pitch and rhythm information important for phrasing in note-based music is available, phrasing is still perceived, primarily in response to changes of intensity and timbre. Implications for electroacoustic music composition and music recommender systems are discussed. PMID:27997625

Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture

PubMed Central

Hwang, Joo-Yeon; Lee, Seung Hun; Go, Min Jin; Kim, Beom-Jun; Kou, Ikuyo; Ikegawa, Shiro; Guo, Yan; Deng, Hong-Wen; Raychaudhuri, Soumya; Kim, Young Jin; Oh, Ji Hee; Kim, Youngdoe; Moon, Sanghoon; Kim, Dong-Joon; Koo, Heejo; Cha, My-Jung; Lee, Min Hye; Yun, Ji Young; Yoo, Hye-Sook; Kang, Young-Ah; Cho, Eun-Hee; Kim, Sang-Wook; Oh, Ki Won; Kang, Moo II; Son, Ho Young; Kim, Shin-Yoon; Kim, Ghi Su; Han, Bok-Ghee; Cho, Yoon Shin; Cho, Myeong-Chan; Lee, Jong-Young; Koh, Jung-Min

2014-01-01

Background Osteoporotic fracture (OF) as a clinical endpoint is a major complication of osteoporosis. To screen for OF susceptibility genes, we performed a genome-wide association study and carried out de novo replication analysis of an East Asian population. Methods Association was tested using a logistic regression analysis. A meta-analysis was performed on the combined results using effect size and standard errors estimated for each study. Results In a combined meta-analysis of a discovery cohort (288 cases and 1139 controls), three hospital based sets in replication stage I (462 cases and 1745 controls), and an independent ethnic group in replication stage II (369 cases and 560 for controls), we identified a new locus associated with OF (rs784288 in the MECOM gene) that showed genome-wide significance (p=3.59×10−8; OR 1.39). RNA interference revealed that a MECOM knockdown suppresses osteoclastogenesis. Conclusions Our findings provide new insights into the genetic architecture underlying OF in East Asians. PMID:23349225

Multifractal analysis of real and imaginary movements: EEG study

NASA Astrophysics Data System (ADS)

Pavlov, Alexey N.; Maksimenko, Vladimir A.; Runnova, Anastasiya E.; Khramova, Marina V.; Pisarchik, Alexander N.

2018-04-01

We study abilities of the wavelet-based multifractal analysis in recognition specific dynamics of electrical brain activity associated with real and imaginary movements. Based on the singularity spectra we analyze electroencephalograms (EEGs) acquired in untrained humans (operators) during imagination of hands movements, and show a possibility to distinguish between the related EEG patterns and the recordings performed during real movements or the background electrical brain activity. We discuss how such recognition depends on the selected brain region.

miRNet - dissecting miRNA-target interactions and functional associations through network-based visual analysis

PubMed Central

Fan, Yannan; Siklenka, Keith; Arora, Simran K.; Ribeiro, Paula; Kimmins, Sarah; Xia, Jianguo

2016-01-01

MicroRNAs (miRNAs) can regulate nearly all biological processes and their dysregulation is implicated in various complex diseases and pathological conditions. Recent years have seen a growing number of functional studies of miRNAs using high-throughput experimental technologies, which have produced a large amount of high-quality data regarding miRNA target genes and their interactions with small molecules, long non-coding RNAs, epigenetic modifiers, disease associations, etc. These rich sets of information have enabled the creation of comprehensive networks linking miRNAs with various biologically important entities to shed light on their collective functions and regulatory mechanisms. Here, we introduce miRNet, an easy-to-use web-based tool that offers statistical, visual and network-based approaches to help researchers understand miRNAs functions and regulatory mechanisms. The key features of miRNet include: (i) a comprehensive knowledge base integrating high-quality miRNA-target interaction data from 11 databases; (ii) support for differential expression analysis of data from microarray, RNA-seq and quantitative PCR; (iii) implementation of a flexible interface for data filtering, refinement and customization during network creation; (iv) a powerful fully featured network visualization system coupled with enrichment analysis. miRNet offers a comprehensive tool suite to enable statistical analysis and functional interpretation of various data generated from current miRNA studies. miRNet is freely available at http://www.mirnet.ca. PMID:27105848

Association between work role stressors and sleep quality.

PubMed

Iwasaki, S; Deguchi, Y; Inoue, K

2018-05-17

Work-related stressors are associated with low sleep quality. However, few studies have reported an association between role stressors and sleep quality. To elucidate the association between role stressors (including role conflict and ambiguity) and sleep quality. Cross-sectional study of daytime workers whose sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Work-related stressors, including role stressors, were assessed using the Generic Job Stress Questionnaire (GJSQ). The association between sleep quality and work-related stressors was investigated by logistic regression analysis. A total of 243 participants completed questionnaires were received (response rate 71%); 86 participants reported poor sleep quality, based on a global PSQI score ≥6. Multivariable logistic regression analysis revealed that higher role ambiguity was associated with global PSQI scores ≥6, and that role conflict was significantly associated with sleep problems, including sleep disturbance and daytime dysfunction. These results suggest that high role stress is associated with low sleep quality, and that this association should be considered an important determinant of the health of workers.

A core microbiome associated with the peritoneal tumors of pseudomyxoma peritonei

PubMed Central

2013-01-01

Background Pseudomyxoma peritonei (PMP) is a malignancy characterized by dissemination of mucus-secreting cells throughout the peritoneum. This disease is associated with significant morbidity and mortality and despite effective treatment options for early-stage disease, patients with PMP often relapse. Thus, there is a need for additional treatment options to reduce relapse rate and increase long-term survival. A previous study identified the presence of both typed and non-culturable bacteria associated with PMP tissue and determined that increased bacterial density was associated with more severe disease. These findings highlighted the possible role for bacteria in PMP disease. Methods To more clearly define the bacterial communities associated with PMP disease, we employed a sequenced-based analysis to profile the bacterial populations found in PMP tumor and mucin tissue in 11 patients. Sequencing data were confirmed by in situ hybridization at multiple taxonomic depths and by culturing. A pilot clinical study was initiated to determine whether the addition of antibiotic therapy affected PMP patient outcome. Main results We determined that the types of bacteria present are highly conserved in all PMP patients; the dominant phyla are the Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. A core set of taxon-specific sequences were found in all 11 patients; many of these sequences were classified into taxonomic groups that also contain known human pathogens. In situ hybridization directly confirmed the presence of bacteria in PMP at multiple taxonomic depths and supported our sequence-based analysis. Furthermore, culturing of PMP tissue samples allowed us to isolate 11 different bacterial strains from eight independent patients, and in vitro analysis of subset of these isolates suggests that at least some of these strains may interact with the PMP-associated mucin MUC2. Finally, we provide evidence suggesting that targeting these bacteria with antibiotic treatment may increase the survival of PMP patients. Conclusions Using 16S amplicon-based sequencing, direct in situ hybridization analysis and culturing methods, we have identified numerous bacterial taxa that are consistently present in all PMP patients tested. Combined with data from a pilot clinical study, these data support the hypothesis that adding antimicrobials to the standard PMP treatment could improve PMP patient survival. PMID:23844722

A full potential inverse method based on a density linearization scheme for wing design

NASA Technical Reports Server (NTRS)

Shankar, V.

1982-01-01

A mixed analysis inverse procedure based on the full potential equation in conservation form was developed to recontour a given base wing to produce density linearization scheme in applying the pressure boundary condition in terms of the velocity potential. The FL030 finite volume analysis code was modified to include the inverse option. The new surface shape information, associated with the modified pressure boundary condition, is calculated at a constant span station based on a mass flux integration. The inverse method is shown to recover the original shape when the analysis pressure is not altered. Inverse calculations for weakening of a strong shock system and for a laminar flow control (LFC) pressure distribution are presented. Two methods for a trailing edge closure model are proposed for further study.

Evidence for Association of the E23K Variant of KCNJ11 Gene with Type 2 Diabetes in Tunisian Population: Population-Based Study and Meta-Analysis

PubMed Central

Lasram, Khaled; Ben Halim, Nizar; Hsouna, Sana; Kefi, Rym; Arfa, Imen; Ghazouani, Welid; Jamoussi, Henda; Benrahma, Houda; Kharrat, Najla; Rebai, Ahmed; Ben Ammar, Slim; Bahri, Sonia; Barakat, Abdelhamid; Abid, Abdelmajid; Abdelhak, Sonia

2014-01-01

Aims. Genetic association studies have reported the E23K variant of KCNJ11 gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations. Methods. We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been evaluated by 2 meta-analyses including all population-based studies among Tunisians and Arabs (2 and 5 populations, resp.). Results. A significant association between the E23K variant and Type 2 diabetes was found (OR = 1.6, 95% CI = 1.14–2.27, and P = 0.007). Furthermore, our meta-analysis has confirmed the significant role of the E23K variant in susceptibility of Type 2 diabetes in Tunisian and Arab populations (OR = 1.29, 95% CI = 1.15–1.46, and P < 10−3 and OR = 1.33, 95% CI = 1.13–1.56, and P = 0.001, resp.). Conclusion. Both case-control and meta-analyses results revealed the significant association between the E23K variant of KCNJ11 and Type 2 diabetes among Tunisians and Arabs. PMID:25165692

Method for computing self-consistent solution in a gun code

DOEpatents

Nelson, Eric M

2014-09-23

Complex gun code computations can be made to converge more quickly based on a selection of one or more relaxation parameters. An eigenvalue analysis is applied to error residuals to identify two error eigenvalues that are associated with respective error residuals. Relaxation values can be selected based on these eigenvalues so that error residuals associated with each can be alternately reduced in successive iterations. In some examples, relaxation values that would be unstable if used alone can be used.

KMgene: a unified R package for gene-based association analysis for complex traits.

PubMed

Yan, Qi; Fang, Zhou; Chen, Wei; Stegle, Oliver

2018-02-09

In this report, we introduce an R package KMgene for performing gene-based association tests for familial, multivariate or longitudinal traits using kernel machine (KM) regression under a generalized linear mixed model (GLMM) framework. Extensive simulations were performed to evaluate the validity of the approaches implemented in KMgene. http://cran.r-project.org/web/packages/KMgene. qi.yan@chp.edu or wei.chen@chp.edu. Supplementary data are available at Bioinformatics online. © The Author(s) 2018. Published by Oxford University Press.

Preeclampsia and Retinopathy of Prematurity in Very-Low-Birth-Weight Infants: A Population-Based Study.

PubMed

Huang, Hsin-Chung; Yang, Hwai-I; Chou, Hung-Chieh; Chen, Chien-Yi; Hsieh, Wu-Shiun; Tsou, Kuo-Inn; Tsao, Po-Nien

2015-01-01

Preeclampsia and retinopathy of prematurity (ROP) are associated with impaired angiogenesis. Previous studies on the relationship between preeclampsia and ROP have produced conflicting results. The goal of this study was to evaluate the association between maternal preeclampsia and ROP using a large population-based cohort of very-low-birth-weight (VLBW) infants from 21 neonatal departments registered in the database of the Premature Baby Foundation of Taiwan. Multivariable logistic regression analysis was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) for preeclampsia with reference to ROP and severe ROP. A total of 5,718 VLBW infants (844 cases with maternal preeclampsia) were included for analysis. The overall incidences of mild and severe ROP were 36.0% and 12.2%, respectively. Univariable analysis showed lower GA and lower birth weight, vaginal delivery, non-SGA, RDS, PDA, sepsis, transfusion, and absence of maternal preeclampsia to be associated with mild and severe ROP development. However, OR (95% CI) adjusted for the variables that were significant according to univariable analysis showed the risks of developing any-stage ROP and severe ROP for maternal preeclampsia to be 1.00 (0.84-1.20) and 0.89 (0.63-1.25), respectively. The results remained unchanged in stratified analyses according to SGA status. Our data showed that maternal preeclampsia was not associated with the subsequent development of any stage or severe ROP in VLBW infants.

A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations.

PubMed

Zhang, Han; Wheeler, William; Hyland, Paula L; Yang, Yifan; Shi, Jianxin; Chatterjee, Nilanjan; Yu, Kai

2016-06-01

Meta-analysis of multiple genome-wide association studies (GWAS) has become an effective approach for detecting single nucleotide polymorphism (SNP) associations with complex traits. However, it is difficult to integrate the readily accessible SNP-level summary statistics from a meta-analysis into more powerful multi-marker testing procedures, which generally require individual-level genetic data. We developed a general procedure called Summary based Adaptive Rank Truncated Product (sARTP) for conducting gene and pathway meta-analysis that uses only SNP-level summary statistics in combination with genotype correlation estimated from a panel of individual-level genetic data. We demonstrated the validity and power advantage of sARTP through empirical and simulated data. We conducted a comprehensive pathway-based meta-analysis with sARTP on type 2 diabetes (T2D) by integrating SNP-level summary statistics from two large studies consisting of 19,809 T2D cases and 111,181 controls with European ancestry. Among 4,713 candidate pathways from which genes in neighborhoods of 170 GWAS established T2D loci were excluded, we detected 43 T2D globally significant pathways (with Bonferroni corrected p-values < 0.05), which included the insulin signaling pathway and T2D pathway defined by KEGG, as well as the pathways defined according to specific gene expression patterns on pancreatic adenocarcinoma, hepatocellular carcinoma, and bladder carcinoma. Using summary data from 8 eastern Asian T2D GWAS with 6,952 cases and 11,865 controls, we showed 7 out of the 43 pathways identified in European populations remained to be significant in eastern Asians at the false discovery rate of 0.1. We created an R package and a web-based tool for sARTP with the capability to analyze pathways with thousands of genes and tens of thousands of SNPs.

A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations

PubMed Central

Zhang, Han; Wheeler, William; Hyland, Paula L.; Yang, Yifan; Shi, Jianxin; Chatterjee, Nilanjan; Yu, Kai

2016-01-01

Meta-analysis of multiple genome-wide association studies (GWAS) has become an effective approach for detecting single nucleotide polymorphism (SNP) associations with complex traits. However, it is difficult to integrate the readily accessible SNP-level summary statistics from a meta-analysis into more powerful multi-marker testing procedures, which generally require individual-level genetic data. We developed a general procedure called Summary based Adaptive Rank Truncated Product (sARTP) for conducting gene and pathway meta-analysis that uses only SNP-level summary statistics in combination with genotype correlation estimated from a panel of individual-level genetic data. We demonstrated the validity and power advantage of sARTP through empirical and simulated data. We conducted a comprehensive pathway-based meta-analysis with sARTP on type 2 diabetes (T2D) by integrating SNP-level summary statistics from two large studies consisting of 19,809 T2D cases and 111,181 controls with European ancestry. Among 4,713 candidate pathways from which genes in neighborhoods of 170 GWAS established T2D loci were excluded, we detected 43 T2D globally significant pathways (with Bonferroni corrected p-values < 0.05), which included the insulin signaling pathway and T2D pathway defined by KEGG, as well as the pathways defined according to specific gene expression patterns on pancreatic adenocarcinoma, hepatocellular carcinoma, and bladder carcinoma. Using summary data from 8 eastern Asian T2D GWAS with 6,952 cases and 11,865 controls, we showed 7 out of the 43 pathways identified in European populations remained to be significant in eastern Asians at the false discovery rate of 0.1. We created an R package and a web-based tool for sARTP with the capability to analyze pathways with thousands of genes and tens of thousands of SNPs. PMID:27362418

Structure-sequence based analysis for identification of conserved regions in proteins

DOEpatents

Zemla, Adam T; Zhou, Carol E; Lam, Marisa W; Smith, Jason R; Pardes, Elizabeth

2013-05-28

Disclosed are computational methods, and associated hardware and software products for scoring conservation in a protein structure based on a computationally identified family or cluster of protein structures. A method of computationally identifying a family or cluster of protein structures in also disclosed herein.

Clinical, biomarker, and genetic predictors of specific types of atrial fibrillation in a community-based cohort: data of the PREVEND study.

PubMed

Hobbelt, Anne H; Siland, Joylene E; Geelhoed, Bastiaan; Van Der Harst, Pim; Hillege, Hans L; Van Gelder, Isabelle C; Rienstra, Michiel

2017-02-01

Atrial fibrillation (AF) may present variously in time, and AF may progress from self-terminating to non-self-terminating AF, and is associated with impaired prognosis. However, predictors of AF types are largely unexplored. We investigate the clinical, biomarker, and genetic predictors of development of specific types of AF in a community-based cohort. We included 8042 individuals (319 with incident AF) of the PREVEND study. Types of AF were compared, and multivariate multinomial regression analysis determined associations with specific types of AF. Mean age was 48.5 ± 12.4 years and 50% were men. The types of incident AF were ascertained based on electrocardiograms; 103(32%) were classified as AF without 2-year recurrence, 158(50%) as self-terminating AF, and 58(18%) as non-self-terminating AF. With multivariate multinomial logistic regression analysis, advancing age (P< 0.001 for all three types) was associated with all AF types, male sex was associated with AF without 2-year recurrence and self-terminating AF (P= 0.031 and P= 0.008, respectively). Increasing body mass index and MR-proANP were associated with both self-terminating (P= 0.009 and P< 0.001) and non-self-terminating AF (P= 0.003 and P< 0.001). The only predictor associated with solely self-terminating AF is prescribed anti-hypertensive treatment (P= 0.019). The following predictors were associated with non-self-terminating AF; lower heart rate (P= 0.018), lipid-lowering treatment prescribed (P= 0.009), and eGFR <60 mL/min/1.73 m2 (P= 0.006). Three known AF-genetic variants (rs6666258, rs6817105, and rs10821415) were associated with self-terminating AF. We found clinical, biomarker and genetic predictors of specific types of incident AF in a community-based cohort. The genetic background seems to play a more important role than modifiable risk factors in self-terminating AF.

Ethnic Differences in the Food Intake Patterns and Its Associated Factors of Adolescents in Kelantan, Malaysia.

PubMed

Abdullah, Nurul-Fadhilah; Teo, Pey Sze; Foo, Leng Huat

2016-09-12

The aim of the study was to identify the ethnic differences in dietary patterns and its association with socio-economic, dietary and lifestyle practices among adolescents in Kelantan, Malaysia. A population-based study of 454 adolescents aged 12 to 19 years was included. A validated food frequency questionnaire was used to assess dietary patterns and three dietary patterns were identified based on the principal component analysis method. Malay adolescents had significantly higher scores for the Western-based food pattern and local-based food pattern, whereas Chinese adolescents showed higher scores for the healthy-based food pattern. Multivariate analyses show that age and physical activity (PA) levels were positively associated with healthy-based food pattern in Malay (All, p < 0.001), whereas higher consumption of eating-out from home (EatOut) (p = 0.014) and fast food (p = 0.041) were negatively associated. High weekly breakfast skipping (p < 0.001) and EatOut (p = 0.003) were positively associated with a Western-based pattern, whereas age (p < 0.001) and household income (p = 0.005) were negatively associated. Higher frequency of daily snacking (p = 0.013) was positively associated with local-based food pattern. For Chinese adolescents, age (p < 0.001), PA levels (p < 0.001) and maternal education level (p = 0.035) showed positive associations with the healthy-based pattern, whereas high EatOut (p = 0.001) and fast food intakes (p = 0.001) were negatively associated. Higher weekly consumption of EatOut (p = 0.007), fast food (p = 0.023) and carbonated beverages (p = 0.023), and daily snacking practice (p = 0.004) were positively associated with higher Western-based food pattern, whereas age (p = 0.004) was inversely associated. This study showed that there were significant differences in dietary patterns and its association factors between Malay and Chinese adolescents. More importantly, these findings suggest that unhealthy dietary and lifestyle practices could increase the risk of adherence to unhealthy Western-based food pattern that is high in fat, sugar and salt contents, and, consequently, increase the risk of developing obesity and metabolic-related disorders during these critical years of growth.

Ethnic Differences in the Food Intake Patterns and Its Associated Factors of Adolescents in Kelantan, Malaysia

PubMed Central

Abdullah, Nurul-Fadhilah; Teo, Pey Sze; Foo, Leng Huat

2016-01-01

Objective: The aim of the study was to identify the ethnic differences in dietary patterns and its association with socio-economic, dietary and lifestyle practices among adolescents in Kelantan, Malaysia. Methods: A population-based study of 454 adolescents aged 12 to 19 years was included. A validated food frequency questionnaire was used to assess dietary patterns and three dietary patterns were identified based on the principal component analysis method. Results: Malay adolescents had significantly higher scores for the Western-based food pattern and local-based food pattern, whereas Chinese adolescents showed higher scores for the healthy-based food pattern. Multivariate analyses show that age and physical activity (PA) levels were positively associated with healthy-based food pattern in Malay (All, p < 0.001), whereas higher consumption of eating-out from home (EatOut) (p = 0.014) and fast food (p = 0.041) were negatively associated. High weekly breakfast skipping (p < 0.001) and EatOut (p = 0.003) were positively associated with a Western-based pattern, whereas age (p < 0.001) and household income (p = 0.005) were negatively associated. Higher frequency of daily snacking (p = 0.013) was positively associated with local-based food pattern. For Chinese adolescents, age (p < 0.001), PA levels (p < 0.001) and maternal education level (p = 0.035) showed positive associations with the healthy-based pattern, whereas high EatOut (p = 0.001) and fast food intakes (p = 0.001) were negatively associated. Higher weekly consumption of EatOut (p = 0.007), fast food (p = 0.023) and carbonated beverages (p = 0.023), and daily snacking practice (p = 0.004) were positively associated with higher Western-based food pattern, whereas age (p = 0.004) was inversely associated. Conclusion: This study showed that there were significant differences in dietary patterns and its association factors between Malay and Chinese adolescents. More importantly, these findings suggest that unhealthy dietary and lifestyle practices could increase the risk of adherence to unhealthy Western-based food pattern that is high in fat, sugar and salt contents, and, consequently, increase the risk of developing obesity and metabolic-related disorders during these critical years of growth. PMID:27626444

An expanded genome-wide association study of type 2 diabetes in Europeans

PubMed Central

Scott, Robert A; Scott, Laura J; Mägi, Reedik; Marullo, Letizia; Gaulton, Kyle J; Kaakinen, Marika; Pervjakova, Natalia; Pers, Tune H; Johnson, Andrew D; Eicher, John D; Jackson, Anne U; Ferreira, Teresa; Lee, Yeji; Ma, Clement; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Qi, Lu; Van Zuydam, Natalie R; Mahajan, Anubha; Chen, Han; Almgren, Peter; Voight, Ben F; Grallert, Harald; Müller-Nurasyid, Martina; Ried, Janina S; Rayner, William N; Robertson, Neil; Karssen, Lennart C; van Leeuwen, Elisabeth M; Willems, Sara M; Fuchsberger, Christian; Kwan, Phoenix; Teslovich, Tanya M; Chanda, Pritam; Li, Man; Lu, Yingchang; Dina, Christian; Thuillier, Dorothee; Yengo, Loic; Jiang, Longda; Sparso, Thomas; Kestler, Hans A; Chheda, Himanshu; Eisele, Lewin; Gustafsson, Stefan; Frånberg, Mattias; Strawbridge, Rona J; Benediktsson, Rafn; Hreidarsson, Astradur B; Kong, Augustine; Sigurðsson, Gunnar; Kerrison, Nicola D; Luan, Jian'an; Liang, Liming; Meitinger, Thomas; Roden, Michael; Thorand, Barbara; Esko, Tõnu; Mihailov, Evelin; Fox, Caroline; Liu, Ching-Ti; Rybin, Denis; Isomaa, Bo; Lyssenko, Valeriya; Tuomi, Tiinamaija; Couper, David J; Pankow, James S; Grarup, Niels; Have, Christian T; Jørgensen, Marit E; Jørgensen, Torben; Linneberg, Allan; Cornelis, Marilyn C; van Dam, Rob M; Hunter, David J; Kraft, Peter; Sun, Qi; Edkins, Sarah; Owen, Katharine R; Perry, John RB; Wood, Andrew R; Zeggini, Eleftheria; Tajes-Fernandes, Juan; Abecasis, Goncalo R; Bonnycastle, Lori L; Chines, Peter S; Stringham, Heather M; Koistinen, Heikki A; Kinnunen, Leena; Sennblad, Bengt; Mühleisen, Thomas W; Nöthen, Markus M; Pechlivanis, Sonali; Baldassarre, Damiano; Gertow, Karl; Humphries, Steve E; Tremoli, Elena; Klopp, Norman; Meyer, Julia; Steinbach, Gerald; Wennauer, Roman; Eriksson, Johan G; Männistö, Satu; Peltonen, Leena; Tikkanen, Emmi; Charpentier, Guillaume; Eury, Elodie; Lobbens, Stéphane; Gigante, Bruna; Leander, Karin; McLeod, Olga; Bottinger, Erwin P; Gottesman, Omri; Ruderfer, Douglas; Blüher, Matthias; Kovacs, Peter; Tonjes, Anke; Maruthur, Nisa M; Scapoli, Chiara; Erbel, Raimund; Jöckel, Karl-Heinz; Moebus, Susanne; de Faire, Ulf; Hamsten, Anders; Stumvoll, Michael; Deloukas, Panagiotis; Donnelly, Peter J; Frayling, Timothy M; Hattersley, Andrew T; Ripatti, Samuli; Salomaa, Veikko; Pedersen, Nancy L; Boehm, Bernhard O; Bergman, Richard N; Collins, Francis S; Mohlke, Karen L; Tuomilehto, Jaakko; Hansen, Torben; Pedersen, Oluf; Barroso, Inês; Lannfelt, Lars; Ingelsson, Erik; Lind, Lars; Lindgren, Cecilia M; Cauchi, Stephane; Froguel, Philippe; Loos, Ruth JF; Balkau, Beverley; Boeing, Heiner; Franks, Paul W; Barricarte Gurrea, Aurelio; Palli, Domenico; van der Schouw, Yvonne T; Altshuler, David; Groop, Leif C; Langenberg, Claudia; Wareham, Nicholas J; Sijbrands, Eric; van Duijn, Cornelia M; Florez, Jose C; Meigs, James B; Boerwinkle, Eric; Gieger, Christian; Strauch, Konstantin; Metspalu, Andres; Morris, Andrew D; Palmer, Colin NA; Hu, Frank B; Thorsteinsdottir, Unnur; Stefansson, Kari; Dupuis, Josée; Morris, Andrew P; Boehnke, Michael; McCarthy, Mark I; Prokopenko, Inga

2017-01-01

To characterise type 2 diabetes (T2D) associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D cases and 132,532 controls of European ancestry after imputation using the 1000 Genomes multi-ethnic reference panel. Promising association signals were followed-up in additional data sets (of 14,545 or 7,397 T2D cases and 38,994 or 71,604 controls). We identified 13 novel T2D-associated loci (p<5×10-8), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common SNVs. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion, and in adipocytes, monocytes and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology. PMID:28566273

Fat mass and obesity-associated gene rs11642015 polymorphism is significantly associated with prediabetes and type 2 diabetes subsequent to adjustment for body mass index.

PubMed

Han, Liyuan; Tang, Linlin; Wang, Changyi; Chen, Zhongwei; Zhang, Tao; Chen, Sihan; Liu, Shengyuan; Peng, Xiaolin; Mai, Yifeng; Duan, Shiwei

2014-09-01

The association of the fat mass and obesity-associated gene ( FTO ) rs11642015 polymorphism with prediabetes, type 2 diabetes and obesity in certain populations has not been previously reported. A population-based study was conducted that included 490 type 2 diabetic, 471 prediabetic and 575 normal subjects. The main outcomes of the study were prediabetes, type 2 diabetes and obesity. Binary logistic regression was performed to estimate the association of FTO rs11642015 with the risk of prediabetes, type 2 diabetes and obesity following adjustment for the corresponding confounders. A meta-analysis was also conducted to evaluate the association between FTO rs11642015 and obesity. FTO rs11642015 was significantly associated with prediabetes in the whole sample under the additive model [odds ratio (OR), 1.50; 95% confidence interval (CI), 1.17-1.93; P=0.002], particularly in females. The polymorphism remained consistently significant following adjustment for age and body mass index (BMI), showing an increased prediabetes risk with an additive effect (OR, 1.55; 95% CI, 1.19-2.01; P=0.001). In addition, a significant association was found for rs11642015 with prediabetes and type 2 diabetes under the dominant model. However, under the stringent Bonferroni's correction there was no evidence of positive associations for FTO rs11642015 with obesity in the whole sample, females or males. Findings of the meta-analysis showed that FTO rs11642015 was not predisposed to obesity. In conclusion, the T allele of FTO rs11642015 is positively associated with an increased risk of prediabetes, even after adjustment for age and BMI, particularly in females. Subjects carrying the CT + TT genotype are predisposed to prediabetes and type 2 diabetes. Therefore, results of the population-based study and follow-up meta-analysis suggested that FTO rs11642015 is not significantly associated with susceptibility to obesity.

A Pooled Analysis on Crizotinib in Treating Chinese Patients with EML4-ALK Positive Non-small-cell Lung Cancer.

PubMed

Li, Yang; Huang, Xin-En

2015-01-01

This analysis was conducted to evaluate the efficacy and safety of crizotinib based regimens in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer. Clinical studies evaluating the efficacy and safety of crizotinib based regimens on response and safety for Chinese patients with EML4-ALK positive non-small-cell lung cancer were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. In crizotinib based regimens, 3 clinical studies which including 128 Chinese patients with EML4-ALK positive non-small-cell lung cancer and treated with crizotinib based regimen were considered eligible for inclusion. Pooled analysis suggested that, in all patients, the pooled RR was 59.3% (76/128) in crizotinib based regimens. ALT/AST mild visual disturbances, nausea, and vomiting were the main side effects. No treatment related death occurred in these crizotinib based treatments. This pooled analysis suggests that crizotinib based regimens are associated with good response rate and accepted toxicities in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer.

Substance use disorder and risk of suicidal ideation, suicide attempt and suicide death: a meta-analysis.

PubMed

Poorolajal, Jalal; Haghtalab, Tahereh; Farhadi, Mehran; Darvishi, Nahid

2016-09-01

This meta-analysis addressed the association between substance use disorder (SUD) and suicide outcomes based on current evidence. We searched PubMed, Web of Science and Scopus until May 2015. We also searched the reference lists of included studies and Psycinfo website. We included observational (cohort, case-control, cross-sectional) studies addressing the association between SUD and suicide. Our outcomes of interest were suicide ideation, suicide attempt and suicide death. For each outcome, we calculated the odds ratio (OR) or risk ratio (RR) with 95% confidence intervals (CI) based on the random-effects model. We identified a total of 12 413 references and included 43 studies with 870 967 participants. There was a significant association between SUD and suicidal ideation: OR 2.04 (95% CI: 1.59, 2.50; I 2 = 88.8%, 16 studies); suicide attempt OR 2.49 (95% CI: 2.00, 2.98; I 2 = 94.3%, 24 studies) and suicide death OR 1.49 (95% CI: 0.97, 2.00; I 2 = 82.7%, 7 studies). Based on current evidence, there is a strong association between SUD and suicide outcomes. However, evidence based on long-term prospective cohort studies is limited and needs further investigation. Moreover, further evidence is required to assess and compare the association between suicide outcomes and different types of illicit drugs, dose-response relationship and the way they are used. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

FARVATX: FAmily-based Rare Variant Association Test for X-linked genes

PubMed Central

Choi, Sungkyoung; Lee, Sungyoung; Qiao, Dandi; Hardin, Megan; Cho, Michael H.; Silverman, Edwin K; Park, Taesung; Won, Sungho

2016-01-01

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease (COPD). Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods. PMID:27325607

FARVATX: Family-Based Rare Variant Association Test for X-Linked Genes.

PubMed

Choi, Sungkyoung; Lee, Sungyoung; Qiao, Dandi; Hardin, Megan; Cho, Michael H; Silverman, Edwin K; Park, Taesung; Won, Sungho

2016-09-01

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease. Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods. © 2016 WILEY PERIODICALS, INC.

A Likelihood-Based Framework for Association Analysis of Allele-Specific Copy Numbers.

PubMed

Hu, Y J; Lin, D Y; Sun, W; Zeng, D

2014-10-01

Copy number variants (CNVs) and single nucleotide polymorphisms (SNPs) co-exist throughout the human genome and jointly contribute to phenotypic variations. Thus, it is desirable to consider both types of variants, as characterized by allele-specific copy numbers (ASCNs), in association studies of complex human diseases. Current SNP genotyping technologies capture the CNV and SNP information simultaneously via fluorescent intensity measurements. The common practice of calling ASCNs from the intensity measurements and then using the ASCN calls in downstream association analysis has important limitations. First, the association tests are prone to false-positive findings when differential measurement errors between cases and controls arise from differences in DNA quality or handling. Second, the uncertainties in the ASCN calls are ignored. We present a general framework for the integrated analysis of CNVs and SNPs, including the analysis of total copy numbers as a special case. Our approach combines the ASCN calling and the association analysis into a single step while allowing for differential measurement errors. We construct likelihood functions that properly account for case-control sampling and measurement errors. We establish the asymptotic properties of the maximum likelihood estimators and develop EM algorithms to implement the corresponding inference procedures. The advantages of the proposed methods over the existing ones are demonstrated through realistic simulation studies and an application to a genome-wide association study of schizophrenia. Extensions to next-generation sequencing data are discussed.

Exploring the Associations among Nutrition, Science, and Mathematics Knowledge for an Integrative, Food-Based Curriculum

ERIC Educational Resources Information Center

Stage, Virginia C.; Kolasa, Kathryn M.; Díaz, Sebastián R.; Duffrin, Melani W.

2018-01-01

Background: Explore associations between nutrition, science, and mathematics knowledge to provide evidence that integrating food/nutrition education in the fourth-grade curriculum may support gains in academic knowledge. Methods: Secondary analysis of a quasi-experimental study. Sample included 438 students in 34 fourth-grade classrooms across…

Demographic and Clinical Characteristics Associated with Engagement in Behavioral Health Treatment among Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Croen, Lisa A.; Shankute, Naomi; Davignon, Meghan; Massolo, Maria L.; Yoshida, Cathleen

2017-01-01

This study investigates demographic and clinical factors associated with initiation, continuation, and adherence to behavioral health treatment (BHT) among children with autism spectrum disorder. Among 293 insured children referred for applied behavior analysis (ABA) based BHT, 23% never initiated treatment. Among those initiating treatment, 31%…

Associations of Psychosocial Factors with the Stress of Infertility Treatment

ERIC Educational Resources Information Center

Schneider, Myra G.; Forthofer, Melinda S.

2005-01-01

This study investigated psychosocial factors thought to be associated with perceived stress over the course of infertility treatment. The research was based on secondary analysis of data from the Study of Marriage, Family, and Life Quality with a sample of 128 people who completed an infertility-related stress instrument at all three measurement…

Association between Terror Attacks and Suicide Attempts

ERIC Educational Resources Information Center

Weizman, Tal; Yagil, Yaron; Schreiber, Shaul

2009-01-01

Based on Durkheim's "Control theory," we explored the association between frequency of terror attacks in Israel and the frequency of suicide attempts admitted to the Emergency Room of a major general hospital in Tel-Aviv (1999-2004). Analysis of the six-year study period as a whole revealed no significant correlation between the…

Association between Contract Teachers and Student Learning in Five Francophone African Countries

ERIC Educational Resources Information Center

Chudgar, Amita

2015-01-01

This article investigates the association between studying with a contract teacher and a student's academic outcomes, using data from five Francophone African countries for two grade levels and two subjects. Based on this analysis, the evidence for or against this form of teacher hiring is inconclusive. The results indicate that these…

Mobile phone use and risk of tumors: a meta-analysis.

PubMed

Myung, Seung-Kwon; Ju, Woong; McDonnell, Diana D; Lee, Yeon Ji; Kazinets, Gene; Cheng, Chih-Tao; Moskowitz, Joel M

2009-11-20

Case-control studies have reported inconsistent findings regarding the association between mobile phone use and tumor risk. We investigated these associations using a meta-analysis. We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library in August 2008. Two evaluators independently reviewed and selected articles based on predetermined selection criteria. Of 465 articles meeting our initial criteria, 23 case-control studies, which involved 37,916 participants (12,344 patient cases and 25,572 controls), were included in the final analyses. Compared with never or rarely having used a mobile phone, the odds ratio for overall use was 0.98 for malignant and benign tumors (95% CI, 0.89 to 1.07) in a random-effects meta-analysis of all 23 studies. However, a significant positive association (harmful effect) was observed in a random-effects meta-analysis of eight studies using blinding, whereas a significant negative association (protective effect) was observed in a fixed-effects meta-analysis of 15 studies not using blinding. Mobile phone use of 10 years or longer was associated with a risk of tumors in 13 studies reporting this association (odds ratio = 1.18; 95% CI, 1.04 to 1.34). Further, these findings were also observed in the subgroup analyses by methodologic quality of study. Blinding and methodologic quality of study were strongly associated with the research group. The current study found that there is possible evidence linking mobile phone use to an increased risk of tumors from a meta-analysis of low-biased case-control studies. Prospective cohort studies providing a higher level of evidence are needed.

Loss-of-Function FANCL Mutations Associate with Severe Fanconi Anemia Overlapping the VACTERL Association.

PubMed

Vetro, Annalisa; Iascone, Maria; Limongelli, Ivan; Ameziane, Najim; Gana, Simone; Della Mina, Erika; Giussani, Ursula; Ciccone, Roberto; Forlino, Antonella; Pezzoli, Laura; Rooimans, Martin A; van Essen, Antoni J; Messa, Jole; Rizzuti, Tommaso; Bianchi, Paolo; Dorsman, Josephine; de Winter, Johan P; Lalatta, Faustina; Zuffardi, Orsetta

2015-05-01

The diagnosis of VACTERL syndrome can be elusive, especially in the prenatal life, due to the presence of malformations that overlap those present in other genetic conditions, including the Fanconi anemia (FA). We report on three VACTERL cases within two families, where the two who arrived to be born died shortly after birth due to severe organs' malformations. The suspicion of VACTERL association was based on prenatal ultrasound assessment and postnatal features. Subsequent chromosome breakage analysis suggested the diagnosis of FA. Finally, by next-generation sequencing based on the analysis of the exome in one family and of a panel of Fanconi genes in the second one, we identified novel FANCL truncating mutations in both families. We used ectopic expression of wild-type FANCL to functionally correct the cellular FA phenotype for both mutations. Our study emphasizes that the diagnosis of FA should be considered when VACTERL association is suspected. Furthermore, we show that loss-of-function mutations in FANCL result in a severe clinical phenotype characterized by early postnatal death. © 2015 WILEY PERIODICALS, INC.

Paradigm Change: Alternate Approaches to Constitutive and Necking Models for Sheet Metal Forming

NASA Astrophysics Data System (ADS)

Stoughton, Thomas B.; Yoon, Jeong Whan

2011-08-01

This paper reviews recent work proposing paradigm changes for the currently popular approach to constitutive and failure modeling, focusing on the use of non-associated flow rules to enable greater flexibility to capture the anisotropic yield and flow behavior of metals using less complex functions than those needed under associated flow to achieve that same level of fidelity to experiment, and on the use of stress-based metrics to more reliably predict necking limits under complex conditions of non-linear forming. The paper discusses motivating factors and benefits in favor of both associated and non-associated flow models for metal forming, including experimental, theoretical, and practical aspects. This review is followed by a discussion of the topic of the forming limits, the limitations of strain analysis, the evidence in favor of stress analysis, the effects of curvature, bending/unbending cycles, triaxial stress conditions, and the motivation for the development of a new type of forming limit diagram based on the effective plastic strain or equivalent plastic work in combination with a directional parameter that accounts for the current stress condition.

Interpreting Meta-Analyses of Genome-Wide Association Studies

PubMed Central

Han, Buhm; Eskin, Eleazar

2012-01-01

Meta-analysis is an increasingly popular tool for combining multiple genome-wide association studies in a single analysis to identify associations with small effect sizes. The effect sizes between studies in a meta-analysis may differ and these differences, or heterogeneity, can be caused by many factors. If heterogeneity is observed in the results of a meta-analysis, interpreting the cause of heterogeneity is important because the correct interpretation can lead to a better understanding of the disease and a more effective design of a replication study. However, interpreting heterogeneous results is difficult. The standard approach of examining the association p-values of the studies does not effectively predict if the effect exists in each study. In this paper, we propose a framework facilitating the interpretation of the results of a meta-analysis. Our framework is based on a new statistic representing the posterior probability that the effect exists in each study, which is estimated utilizing cross-study information. Simulations and application to the real data show that our framework can effectively segregate the studies predicted to have an effect, the studies predicted to not have an effect, and the ambiguous studies that are underpowered. In addition to helping interpretation, the new framework also allows us to develop a new association testing procedure taking into account the existence of effect. PMID:22396665

Association of Alzheimer's disease GWAS loci with MRI markers of brain aging.

PubMed

Chauhan, Ganesh; Adams, Hieab H H; Bis, Joshua C; Weinstein, Galit; Yu, Lei; Töglhofer, Anna Maria; Smith, Albert Vernon; van der Lee, Sven J; Gottesman, Rebecca F; Thomson, Russell; Wang, Jing; Yang, Qiong; Niessen, Wiro J; Lopez, Oscar L; Becker, James T; Phan, Thanh G; Beare, Richard J; Arfanakis, Konstantinos; Fleischman, Debra; Vernooij, Meike W; Mazoyer, Bernard; Schmidt, Helena; Srikanth, Velandai; Knopman, David S; Jack, Clifford R; Amouyel, Philippe; Hofman, Albert; DeCarli, Charles; Tzourio, Christophe; van Duijn, Cornelia M; Bennett, David A; Schmidt, Reinhold; Longstreth, William T; Mosley, Thomas H; Fornage, Myriam; Launer, Lenore J; Seshadri, Sudha; Ikram, M Arfan; Debette, Stephanie

2015-04-01

Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta ± SE = -0.047 ± 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons. Copyright © 2015 Elsevier Inc. All rights reserved.

Dental Composite Restorations and Neuropsychological Development in Children: Treatment Level Analysis from a Randomized Clinical Trial

PubMed Central

Maserejian, Nancy N.; Trachtenberg, Felicia L.; Hauser, Russ; McKinlay, Sonja; Shrader, Peter; Bellinger, David C.

2012-01-01

Background Resin-based dental restorations may intra-orally release their components and bisphenol A. Gestational bisphenol A exposure has been associated with poorer executive functioning in children. Objectives To examine whether exposure to resin-based composite restorations is associated with neuropsychological development in children. Methods Secondary analysis of treatment level data from the New England Children’s Amalgam Trial, a 2-group randomized safety trial conducted from 1997–2006. Children (N=534) aged 6–10 y with >2 posterior tooth caries were randomized to treatment with amalgam or resin-based composites (bisphenol-A-diglycidyl-dimethacrylate-composite for permanent teeth; urethane dimethacrylate-based polyacid-modified compomer for primary teeth). Neuropsychological function at 4- and 5-year follow-up (N=444) was measured by a battery of tests of executive function, intelligence, memory, visual-spatial skills, verbal fluency, and problem-solving. Multivariable generalized linear regression models were used to examine the association between composite exposure levels and changes in neuropsychological test scores from baseline to follow-up. For comparison, data on children randomized to amalgam treatment were similarly analyzed. Results With greater exposure to either dental composite material, results were generally consistent in the direction of slightly poorer changes in tests of intelligence, achievement or memory, but there were no statistically significant associations. For the four primary measures of executive function, scores were slightly worse with greater total composite exposure, but statistically significant only for the test of Letter Fluency (10-surface-years β= −0.8, SE=0.4, P=0.035), and the subtest of color naming (β= −1.5, SE=0.5, P=0.004) in the Stroop Color-Word Interference Test. Multivariate analysis of variance confirmed that the negative associations between composite level and executive function were not statistically significant (MANOVA P=0.18). Results for greater amalgam exposure were mostly nonsignificant in the opposite direction of slightly improved scores over follow-up. Conclusions Dental composite restorations had statistically insignificant associations of small magnitude with impairments in neuropsychological test change scores over 4- or 5-years of follow-up in this trial. PMID:22906860

Are obesity and body fat distribution associated with low back pain in women? A population-based study of 1128 Spanish twins.

PubMed

Dario, Amabile B; Ferreira, Manuela L; Refshauge, Kathryn; Sánchez-Romera, Juan F; Luque-Suarez, Alejandro; Hopper, John L; Ordoñana, Juan R; Ferreira, Paulo H

2016-04-01

To investigate the relationship between different measures of obesity and chronic low back pain (LBP) using a within-pair twin case-control design that adjusts for genetics and early shared environment. A cross-sectional association between lifetime prevalence of chronic LBP and different measures of obesity (body mass index-BMI; percent body fat; waist circumference; waist-hip ratio) was investigated in 1128 female twins in three stages: (i) total sample analysis; (ii) within-pair case-control analysis for monozygotic (MZ) and dizygotic (DZ) twins together; (iii) within-pair case-control analysis separated by DZ and MZ. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. BMI (OR 1.12; 95% CI 1.02-1.26) and percent body fat (OR 1.15; 95% CI 1.01-1.32) were weakly associated with lifetime prevalence of chronic LBP in the total sample analysis but were absent when shared environment and genetic factors were adjusted for using the within-pair case-control analysis. Greater waist-hip ratios were associated with smaller prevalence estimates of chronic LBP in the within-pair case-control analysis with both MZ and DZ twins (OR 0.67; 95% CI 0.47-0.94). However, this association did not remain after the full adjustment for genetic factors in the MZ within-pair case-control analysis. BMI, percent of fat mass and greater depositions of fat and mass around the hips are associated with increases in chronic LBP prevalence in women but these associations are small and appear to be confounded by the effects of genetics and early shared environment. Therefore, our results do not support a causal direct relationship between obesity and chronic LBP.

Wavelet-based image analysis system for soil texture analysis

NASA Astrophysics Data System (ADS)

Sun, Yun; Long, Zhiling; Jang, Ping-Rey; Plodinec, M. John

2003-05-01

Soil texture is defined as the relative proportion of clay, silt and sand found in a given soil sample. It is an important physical property of soil that affects such phenomena as plant growth and agricultural fertility. Traditional methods used to determine soil texture are either time consuming (hydrometer), or subjective and experience-demanding (field tactile evaluation). Considering that textural patterns observed at soil surfaces are uniquely associated with soil textures, we propose an innovative approach to soil texture analysis, in which wavelet frames-based features representing texture contents of soil images are extracted and categorized by applying a maximum likelihood criterion. The soil texture analysis system has been tested successfully with an accuracy of 91% in classifying soil samples into one of three general categories of soil textures. In comparison with the common methods, this wavelet-based image analysis approach is convenient, efficient, fast, and objective.

LRP-1 polymorphism is associated with global and regional amyloid load in Alzheimer's disease in humans in-vivo

PubMed Central

Grimmer, Timo; Goldhardt, Oliver; Guo, Liang-Hao; Yousefi, Behrooz H.; Förster, Stefan; Drzezga, Alexander; Sorg, Christian; Alexopoulos, Panagiotis; Förstl, Hans; Kurz, Alexander; Perneczky, Robert

2014-01-01

Objective Impaired amyloid clearance has been proposed to contribute to β-amyloid deposition in sporadic late-onset Alzheimer's disease (AD). Low density lipoprotein receptor-related protein 1 (LRP-1) is involved in the active outward transport of β-amyloid across the blood–brain barrier (BBB). The C667T polymorphism (rs1799986) of the LRP-1 gene has been inconsistently associated with AD in genetic studies. We aimed to elucidate the association of this polymorphism with in-vivo brain amyloid load of AD patients using amyloid PET with [11C]PiB. Materials and methods 72 patients with very mild to moderate AD were examined with amyloid PET and C667T polymorphism was obtained using TaqMan PCR assays. The association of C667T polymorphism with global and regional amyloid load was calculated using linear regression and voxel based analysis, respectively. The effect of the previously identified modulator of amyloid uptake, the apolipoprotein E genotype, on this association was also determined. Results The regression analysis between amyloid load and C667T polymorphism was statistically significant (p = 0.046, β = 0.236). In an additional analysis ApoE genotype and gender were identified to explain further variability of amyloid load. Voxel based analysis revealed a significant (p < 0.05) association between C667T polymorphism and amyloid uptake in the temporo-parietal cortex bilaterally. ApoE did not interact significantly with the LRP-1 polymorphism. Discussion In conclusion, C667T polymorphism of LRP-1 is moderately but significantly associated with global and regional amyloid deposition in AD. The relationship appears to be independent of the ApoE genotype. This finding is compatible with the hypothesis that impaired amyloid clearance contributes to amyloid deposition in late-onset sporadic AD. PMID:24596678

Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome.

PubMed

Zemojtel, Tomasz; Köhler, Sebastian; Mackenroth, Luisa; Jäger, Marten; Hecht, Jochen; Krawitz, Peter; Graul-Neumann, Luitgard; Doelken, Sandra; Ehmke, Nadja; Spielmann, Malte; Oien, Nancy Christine; Schweiger, Michal R; Krüger, Ulrike; Frommer, Götz; Fischer, Björn; Kornak, Uwe; Flöttmann, Ricarda; Ardeshirdavani, Amin; Moreau, Yves; Lewis, Suzanna E; Haendel, Melissa; Smedley, Damian; Horn, Denise; Mundlos, Stefan; Robinson, Peter N

2014-09-03

Less than half of patients with suspected genetic disease receive a molecular diagnosis. We have therefore integrated next-generation sequencing (NGS), bioinformatics, and clinical data into an effective diagnostic workflow. We used variants in the 2741 established Mendelian disease genes [the disease-associated genome (DAG)] to develop a targeted enrichment DAG panel (7.1 Mb), which achieves a coverage of 20-fold or better for 98% of bases. Furthermore, we established a computational method [Phenotypic Interpretation of eXomes (PhenIX)] that evaluated and ranked variants based on pathogenicity and semantic similarity of patients' phenotype described by Human Phenotype Ontology (HPO) terms to those of 3991 Mendelian diseases. In computer simulations, ranking genes based on the variant score put the true gene in first place less than 5% of the time; PhenIX placed the correct gene in first place more than 86% of the time. In a retrospective test of PhenIX on 52 patients with previously identified mutations and known diagnoses, the correct gene achieved a mean rank of 2.1. In a prospective study on 40 individuals without a diagnosis, PhenIX analysis enabled a diagnosis in 11 cases (28%, at a mean rank of 2.4). Thus, the NGS of the DAG followed by phenotype-driven bioinformatic analysis allows quick and effective differential diagnostics in medical genetics. Copyright © 2014, American Association for the Advancement of Science.

Risk factors for financial hardship in patients receiving adjuvant chemotherapy for colon cancer: a population-based exploratory analysis.

PubMed

Shankaran, Veena; Jolly, Sanjay; Blough, David; Ramsey, Scott D

2012-05-10

Characteristics that predispose patients to financial hardship during cancer treatment are poorly understood. We therefore conducted a population-based exploratory analysis of potential factors associated with financial hardship and treatment nonadherence during and following adjuvant chemotherapy for colon cancer. Patients diagnosed with stage III colon cancer between 2008 and 2010 were identified from a population-based cancer registry representing 13 counties in Washington state. Patients were asked to complete a comprehensive survey on treatment-related costs. Patients were considered to have experienced financial hardship if they accrued debt, sold or refinanced their home, borrowed money from friends or family, or experienced a 20% or greater decline in their annual income as a result of treatment-related expenses. Logistic regression analysis was used to investigate factors associated with financial hardship and treatment nonadherence. A total of 284 responses were obtained from 555 eligible patients (response rate, 51.2%). Nearly all patients in the final sample were insured during treatment. In this sample, 38% of patients reported one or more financial hardships as a result of treatment. The factors most closely associated with treatment-related financial hardship were younger age and lower annual household income. Younger age, lower income, and unemployment or disability (which occurred in most instances following diagnosis) were most closely associated with treatment nonadherence. A significant proportion of patients undergoing adjuvant chemotherapy for stage III colon cancer may experience financial hardship, despite having health insurance coverage. Interventions to help at-risk patients early on during therapy may prevent long-term financial adverse effects.

Cost analysis of strategies to reduce blood culture contamination in the emergency department: sterile collection kits and phlebotomy teams.

PubMed

Self, Wesley H; Talbot, Thomas R; Paul, Barbara R; Collins, Sean P; Ward, Michael J

2014-08-01

Blood culture collection practices that reduce contamination, such as sterile blood culture collection kits and phlebotomy teams, increase up-front costs for collecting cultures but may lead to net savings by eliminating downstream costs associated with contamination. The study objective was to compare overall hospital costs associated with 3 collection strategies: usual care, sterile kits, and phlebotomy teams. Cost analysis. This analysis was conducted from the perspective of a hospital leadership team selecting a blood culture collection strategy for an adult emergency department (ED) with 8,000 cultures drawn annually. Total hospital costs associated with 3 strategies were compared: (1) usual care, with nurses collecting cultures without a standardized protocol; (2) sterile kits, with nurses using a dedicated sterile collection kit; and (3) phlebotomy teams, with cultures collected by laboratory-based phlebotomists. In the base case, contamination rates associated with usual care, sterile kits, and phlebotomy teams were assumed to be 4.34%, 1.68%, and 1.10%, respectively. Total hospital costs included costs of collecting cultures and hospitalization costs according to culture results (negative, true positive, and contaminated). Compared with usual care, annual net savings using the sterile kit and phlebotomy team strategies were $483,219 and $288,980, respectively. Both strategies remained less costly than usual care across a broad range of sensitivity analyses. EDs with high blood culture contamination rates should strongly consider evidence-based strategies to reduce contamination. In addition to improving quality, implementing a sterile collection kit or phlebotomy team strategy is likely to result in net cost savings.

A system view and analysis of essential hypertension.

PubMed

Botzer, Alon; Grossman, Ehud; Moult, John; Unger, Ron

2018-05-01

The goal of this study was to investigate genes associated with essential hypertension from a system perspective, making use of bioinformatic tools to gain insights that are not evident when focusing at a detail-based resolution. Using various databases (pathways, Genome Wide Association Studies, knockouts etc.), we compiled a set of about 200 genes that play a major role in hypertension and identified the interactions between them. This enabled us to create a protein-protein interaction network graph, from which we identified key elements, based on graph centrality analysis. Enriched gene regulatory elements (transcription factors and microRNAs) were extracted by motif finding techniques and knowledge-based tools. We found that the network is composed of modules associated with functions such as water retention, endothelial vasoconstriction, sympathetic activity and others. We identified the transcription factor SP1 and the two microRNAs miR27 (a and b) and miR548c-3p that seem to play a major role in regulating the network as they exert their control over several modules and are not restricted to specific functions. We also noticed that genes involved in metabolic diseases (e.g. insulin) are central to the network. We view the blood-pressure regulation mechanism as a system-of-systems, composed of several contributing subsystems and pathways rather than a single module. The system is regulated by distributed elements. Understanding this mode of action can lead to a more precise treatment and drug target discovery. Our analysis suggests that insulin plays a primary role in hypertension, highlighting the tight link between essential hypertension and diseases associated with the metabolic syndrome.

Syringohydromyelia in Patients with Chiari I Malformation: A Retrospective Analysis.

PubMed

Gad, K A; Yousem, D M

2017-09-01

The association of syringohydromyelia with Chiari I malformation has a wide range, between 23% and 80% of cases in the current literature. In our experience, this range might be overestimated compared with our observations in clinical practice. Because there is an impact of Chiari I malformation-associated syringohydromyelia on morbidity and surgical intervention, its diagnosis is critical in this patient population. Identifying related variables on the basis of imaging would also help identify those patients at risk of syrinx formation during their course of disease. We performed a retrospective analysis of the MR imaging studies of 108 consecutive cases of Chiari I malformation. A multitude of factors associated with syrinx formation were investigated, including demographic, morphometric, osseous, and dynamic CSF flow evaluation. Thirty-nine of 108 (36.1%) patients with Chiari I malformation had syringohydromyelia. On the basis of receiver operating characteristic curve analysis, a skull base angle (nasion-sella-basion) of 135° was found to be a statistically significant classifier of patients with Chiari I malformation with or without syringohydromyelia. Craniocervical junction osseous anomalies (OR = 4.3, P = .001) and a skull base angle of >135° (OR = 4.8, P = .0006) were most predictive of syrinx formation. Pediatric patients (younger than 18 years of age) who developed syringohydromyelia were more likely to have associated skull base osseous anomalies than older individuals ( P = .01). Our findings support evidence of the role of foramen magnum blockage from osseous factors in the development of syringohydromyelia in patients with Chiari I malformation. © 2017 by American Journal of Neuroradiology.

Exposure to non-ionizing electromagnetic radiation from mobile telephony and the association with psychiatric symptoms.

PubMed

Silva, Denize Francisca da; Barros, Warley Rocha; Almeida, Maria da Conceição Chagas de; Rêgo, Marco Antônio Vasconcelos

2015-10-01

The aim of this study was to investigate the association between exposure to non-ionizing electromagnetic radiation from mobile phone base stations and psychiatric symptoms. In a cross-sectional study in Salvador, Bahia State, Brazil, 440 individuals were interviewed. Psychiatric complaints and diagnoses were the dependent variables and distance from the individual's residence to the base station was considered the main independent variable. Hierarchical logistic regression analysis was conducted to assess confounding. An association was observed between psychiatric symptoms and residential proximity to the base station and different forms of mobile phone use (making calls with weak signal coverage, keeping the mobile phone close to the body, having two or more chips, and never turning off the phone while sleeping), and with the use of other electronic devices. The study concluded that exposure to electromagnetic radiation from mobile phone base stations and other electronic devices was associated with psychiatric symptoms, independently of gender, schooling, and smoking status. The adoption of precautionary measures to reduce such exposure is recommended.

Is IQ in Childhood Associated with Suicidal Thoughts and Attempts? Findings from the Mater University Study of Pregnancy and Its Outcomes

ERIC Educational Resources Information Center

Alati, Rosa; Gunnell, David; Najman, Jake; Williams, Gail; Lawlor, Debbie

2009-01-01

This study explores associations of IQ at age 14 with adult symptoms of suicidal thoughts and attempts at age 21. Analysis was based on the Mater University Study of Pregnancy and its outcomes, an Australian prospective birth cohort study started in Brisbane Australia in 1981. We assessed associations with suicide thoughts, plans, and attempts. We…

A Transcript Analysis of Graduates of Three Community College of Philadelphia Curricula between the Years 1985 and 1992. Institutional Research Report #83.

ERIC Educational Resources Information Center

Terzian, Aram L.; Obetz, Wayne S.

A study was conducted at the Community College of Philadelphia (CCP) to examine the course-taking patterns of 94 graduates of the associate in arts (AA) curriculum, 1,957 graduates of the association in general studies (AGS) curriculum, and 99 graduates of the associate in science (AS) curriculum. Using a computer-based approach to transcript…

Egg consumption and risk of bladder cancer: a meta-analysis.

PubMed

Li, Fei; Zhou, You; Hu, Rui-ting; Hou, Li-na; Du, Yue-Jun; Zhang, Xin-ji; Olkkonen, Vesa M; Tan, Wan-long

2013-01-01

The findings of epidemiologic studies on the association between egg consumption and bladder cancer risk remain conflicting. We conducted a meta-analysis to clarify the potential association between egg consumption and bladder cancer risk. Four cohort studies and 9 case-control studies in the PubMed database through February 2012 were identified on egg consumption and risk of bladder cancer involving 2715 cases and 184,727 participants. Random-effects models were used to calculate the summary relative risk estimates (SRRE) based on the highest compared with the lowest category of egg consumption. In addition, we performed stratified analyses and sensitivity and dose-response analyses to examine the association. Overall, no significant association was observed between egg consumption and bladder cancer (SRRE = 1.11 95% CI: 0.90-1.35). However, increased risk of bladder cancer was detected in North/South America (SRRE = 1.40 95% CI: 1.05-1.86) and, moreover, fried egg intake positively associated with bladder cancer as well (SRRE = 2.04, 95% CI: 1.41-2.95). In conclusion, our findings suggest no significant association between egg consumption and bladder cancer risk, except for a possible positive relationship with the intake of fried eggs based on the limited number of studies. Additional studies, especially large prospective cohort studies, are warranted to confirm these findings.

[Family-based association study of a variable number of tandem repeat polymorphism of DAT1 gene with Tourette syndrome in a Chinese Han population].

PubMed

Zheng, Lanlan; Han, Zhen-liang; Zhang, Xin-hua; Wang, Xue-qin; Jiang, Wei-hua; Yi, Ming-ji; Liu, Shi-guo

2013-10-01

To assess the association of a 40 bp variable number of tandem repeat (VNTR) polymorphism within 3 untranslated region of dopamine transporter gene (DAT1) with Tourette syndrome (TS) in a Chinese Han population. A total of 160 TS patients and their parents were recruited. The VNTR polymorphism was detected with polymerase chain reaction-VNTR analysis, and its association with TS and its subtypes were assessed through a family-based association study comprising transmission disequilibrium test (TDT) and haplotype relative risk (HRR) analysis. The repeat numbers at the DAT1 40 bp locus were 11, 10, 9, 7.5 and 7 among the patients and their parents, with the most common type being a 10-repeat allele. No significant association was detected between the polymorphism and TS (TDT: X ² = 0.472, df = 1, P = 0.583; HRR: X ² = 0.313, P = 0.576, OR = 0.855, 95%CI: 0.493-1.481). Our data suggested that the VNTR polymorphism of DAT1 gene is not associated with susceptibility to TS in Chinese Han population. However, our results are to be validated in larger sets of patients collected from other populations.

Divergence in Morris Water Maze-Based Cognitive Performance under Chronic Stress Is Associated with the Hippocampal Whole Transcriptomic Modification in Mice

PubMed Central

Jung, Seung H.; Brownlow, Milene L.; Pellegrini, Matteo; Jankord, Ryan

2017-01-01

Individual susceptibility determines the magnitude of stress effects on cognitive function. The hippocampus, a brain region of memory consolidation, is vulnerable to stressful environments, and the impact of stress on hippocampus may determine individual variability in cognitive performance. Therefore, the purpose of this study was to define the relationship between the divergence in spatial memory performance under chronically unpredictable stress and an associated transcriptomic alternation in hippocampus, the brain region of spatial memory consolidation. Multiple strains of BXD (B6 × D2) recombinant inbred mice went through a 4-week chronic variable stress (CVS) paradigm, and the Morris water maze (MWM) test was conducted during the last week of CVS to assess hippocampal-dependent spatial memory performance and grouped animals into low and high performing groups based on the cognitive performance. Using hippocampal whole transcriptome RNA-sequencing data, differential expression, PANTHER analysis, WGCNA, Ingenuity's upstream regulator analysis in the Ingenuity Pathway Analysis® and phenotype association analysis were conducted. Our data identified multiple genes and pathways that were significantly associated with chronic stress-associated cognitive modification and the divergence in hippocampal dependent memory performance under chronic stress. Biological pathways associated with memory performance following chronic stress included metabolism, neurotransmitter and receptor regulation, immune response and cellular process. The Ingenuity's upstream regulator analysis identified 247 upstream transcriptional regulators from 16 different molecule types. Transcripts predictive of cognitive performance under high stress included genes that are associated with a high occurrence of Alzheimer's and cognitive impairments (e.g., Ncl, Eno1, Scn9a, Slc19a3, Ncstn, Fos, Eif4h, Copa, etc.). Our results show that the variable effects of chronic stress on the hippocampal transcriptome are related to the ability to complete the MWM task and that the modulations of specific pathways are indicative of hippocampal dependent memory performance. Thus, the divergence in spatial memory performance following chronic stress is related to the unique pattern of gene expression within the hippocampus. PMID:28912681

78 FR 63448 - Notice of Decision To Allow Interstate Movement of Sapote Fruit From Puerto Rico Into the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... States of fresh sapote fruit from Puerto Rico. Based on the findings of a pest risk analysis, which we... announcing the availability of the pest risk analysis that evaluates the risks associated with the interstate... measures if: (1) No comments were received on the pest risk analysis; (2) the comments on the pest risk...

Land quality, sustainable development and environmental degradation in agricultural districts: A computational approach based on entropy indexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zambon, Ilaria, E-mail: ilaria.zambon@unitus.it; Colantoni, Andrea; Carlucci, Margherita

Land Degradation (LD) in socio-environmental systems negatively impacts sustainable development paths. This study proposes a framework to LD evaluation based on indicators of diversification in the spatial distribution of sensitive land. We hypothesize that conditions for spatial heterogeneity in a composite index of land sensitivity are more frequently associated to areas prone to LD than spatial homogeneity. Spatial heterogeneity is supposed to be associated with degraded areas that act as hotspots for future degradation processes. A diachronic analysis (1960–2010) was performed at the Italian agricultural district scale to identify environmental factors associated with spatial heterogeneity in the degree of landmore » sensitivity to degradation based on the Environmentally Sensitive Area Index (ESAI). In 1960, diversification in the level of land sensitivity measured using two common indexes of entropy (Shannon's diversity and Pielou's evenness) increased significantly with the ESAI, indicating a high level of land sensitivity to degradation. In 2010, surface area classified as “critical” to LD was the highest in districts with diversification in the spatial distribution of ESAI values, confirming the hypothesis formulated above. Entropy indexes, based on observed alignment with the concept of LD, constitute a valuable base to inform mitigation strategies against desertification. - Highlights: • Spatial heterogeneity is supposed to be associated with degraded areas. • Entropy indexes can inform mitigation strategies against desertification. • Assessing spatial diversification in the degree of land sensitivity to degradation. • Mediterranean rural areas have an evident diversity in agricultural systems. • A diachronic analysis carried out at the Italian agricultural district scale.« less

Association Between Obstetric Mode of Delivery and Autism Spectrum Disorder: A Population-Based Sibling Design Study.

PubMed

Curran, Eileen A; Dalman, Christina; Kearney, Patricia M; Kenny, Louise C; Cryan, John F; Dinan, Timothy G; Khashan, Ali S

2015-09-01

Because the rates of cesarean section (CS) are increasing worldwide, it is becoming increasingly important to understand the long-term effects that mode of delivery may have on child development. To investigate the association between obstetric mode of delivery and autism spectrum disorder (ASD). Perinatal factors and ASD diagnoses based on the International Classification of Diseases, Ninth Revision (ICD-9),and the International Statistical Classification of Diseases, 10th Revision (ICD-10),were identified from the Swedish Medical Birth Register and the Swedish National Patient Register. We conducted stratified Cox proportional hazards regression analysis to examine the effect of mode of delivery on ASD. We then used conditional logistic regression to perform a sibling design study, which consisted of sibling pairs discordant on ASD status. Analyses were adjusted for year of birth (ie, partially adjusted) and then fully adjusted for various perinatal and sociodemographic factors. The population-based cohort study consisted of all singleton live births in Sweden from January 1, 1982, through December 31, 2010. Children were followed up until first diagnosis of ASD, death, migration, or December 31, 2011 (end of study period), whichever came first. The full cohort consisted of 2,697,315 children and 28,290 cases of ASD. Sibling control analysis consisted of 13,411 sibling pairs. Obstetric mode of delivery defined as unassisted vaginal delivery (VD), assisted VD, elective CS, and emergency CS (defined by before or after onset of labor). The ASD status as defined using codes from the ICD-9 (code 299) and ICD-10 (code F84). In adjusted Cox proportional hazards regression analysis, elective CS (hazard ratio, 1.21; 95% CI, 1.15-1.27) and emergency CS (hazard ratio, 1.15; 95% CI, 1.10-1.20) were associated with ASD when compared with unassisted VD. In the sibling control analysis, elective CS was not associated with ASD in partially (odds ratio [OR], 0.97; 95% CI, 0.85-1.11) or fully adjusted (OR, 0.89; 95% CI, 0.76-1.04) models. Emergency CS was significantly associated with ASD in partially adjusted analysis (OR, 1.20; 95% CI, 1.06-1.36), but this effect disappeared in the fully adjusted model (OR, 0.97; 95% CI, 0.85-1.11). This study confirms previous findings that children born by CS are approximately 20% more likely to be diagnosed as having ASD. However, the association did not persist when using sibling controls, implying that this association is due to familial confounding by genetic and/or environmental factors.

Population-based studies of antithyroid drugs and sudden cardiac death

PubMed Central

van Noord, Charlotte; Sturkenboom, Miriam C J M; Straus, Sabine M J M; Hofman, Albert; Witteman, Jacqueline C M; Stricker, Bruno H Ch

2009-01-01

AIM Thyroid free T4 is associated with QTc-interval prolongation, which is a risk factor for sudden cardiac death (SCD). Hyperthyroidism has been associated with SCD in case reports, but there are no population-based studies confirming this. The aim was to investigate whether use of antithyroid drugs (as a direct cause or as an indicator of poorly controlled hyperthyroidism) is associated with an increased risk of SCD. METHODS We studied the occurrence of SCD in a two-step procedure in two different Dutch populations. First, the prospective population-based Rotterdam Study including 7898 participants (≥55 years old). Second, we used the Integrated Primary Care Information (IPCI) database, which is a longitudinal general practice research database to see whether we could replicate results from the first study. Drug use at the index date was assessed with prescription information from automated pharmacies (Rotterdam Study) or drug prescriptions from general practices (IPCI). We used a Cox proportional hazards model in a cohort analysis, adjusted for age, gender and use of QTc prolonging drugs (Rotterdam Study) and conditional logistic regression analysis in a case–control analysis, matched for age, gender, practice and calendar time and adjusted for arrhythmia and cerebrovascular ischaemia (IPCI). RESULTS In the Rotterdam Study, 375 participants developed SCD during follow-up. Current use of antithyroid drugs was associated with SCD [adjusted hazard ratio 3.9; 95% confidence interval (CI) 1.7, 8.7]. IPCI included 1424 cases with SCD and 14 443 controls. Also in IPCI, current use of antithyroid drugs was associated with SCD (adjusted odds ratio 2.9; 95% CI 1.1, 7.4). CONCLUSIONS Use of antithyroid drugs was associated with a threefold increased risk of SCD. Although this might be directly caused by antithyroid drug use, it might be more readily explained by underlying poorly controlled hyperthyroidism, since treated patients who developed SCD still had low thyroid-stimulating hormone levels shortly before death. PMID:19740403

Karyotype Analysis Activity: A Constructivist Learning Design

ERIC Educational Resources Information Center

Ahmed, Noveera T.

2015-01-01

This classroom activity is based on a constructivist learning design and engages students in physically constructing a karyotype of three mock patients. Students then diagnose the chromosomal aneuploidy based on the karyotype, list the symptoms associated with the disorder, and discuss the implications of the diagnosis. This activity is targeted…

Professional Learning: A Fuzzy Logic-Based Modelling Approach

ERIC Educational Resources Information Center

Gravani, M. N.; Hadjileontiadou, S. J.; Nikolaidou, G. N.; Hadjileontiadis, L. J.

2007-01-01

Studies have suggested that professional learning is influenced by two key parameters, i.e., climate and planning, and their associated variables (mutual respect, collaboration, mutual trust, supportiveness, openness). In this paper, we applied analysis of the relationships between the proposed quantitative, fuzzy logic-based model and a series of…

Knowledge Acquisition Using Linguistic-Based Knowledge Analysis

Treesearch

Daniel L. Schmoldt

1998-01-01

Most knowledge-based system developmentefforts include acquiring knowledge from one or more sources. difficulties associated with this knowledge acquisition task are readily acknowledged by most researchers. While a variety of knowledge acquisition methods have been reported, little has been done to organize those different methods and to suggest how to apply them...

Preschoolers' Mathematics Skills and Behavior: Analysis of a National Sample

ERIC Educational Resources Information Center

Dobbs-Oates, Jennifer; Robinson, Chanele

2012-01-01

This study investigated the association between children's mathematical skills and their behavior in the prekindergarten year in a national sample of children attending center-based child care. The sample consisted of approximately 5,400 preschoolers in center-based care from the Early Childhood Longitudinal Study--Birth Cohort. Children's math…

Do Functional Behavioral Assessments Improve Intervention Effectiveness for Students with ADHD? A Single-Subject Meta-Analysis

ERIC Educational Resources Information Center

Miller, Faith G.

2011-01-01

The primary purpose of this quantitative synthesis of single-subject research was to investigate the relative effectiveness of function-based and non-function-based behavioral interventions for students diagnosed with attention-deficit/hyperactivity disorder. In addition, associations between various participant, assessment, and intervention…

A Modified Importance-Performance Framework for Evaluating Recreation-Based Experiential Learning Programs

ERIC Educational Resources Information Center

Pitas, Nicholas; Murray, Alison; Olsen, Max; Graefe, Alan

2017-01-01

This article describes a modified importance-performance framework for use in evaluation of recreation-based experiential learning programs. Importance-performance analysis (IPA) provides an effective and readily applicable means of evaluating many programs, but the near universal satisfaction associated with recreation inhibits the use of IPA in…

Genome-wide and gene-based association implicates FRMD6 in Alzheimer disease.

PubMed

Hong, Mun-Gwan; Reynolds, Chandra A; Feldman, Adina L; Kallin, Mikael; Lambert, Jean-Charles; Amouyel, Philippe; Ingelsson, Erik; Pedersen, Nancy L; Prince, Jonathan A

2012-03-01

Genome-wide association studies (GWAS) that allow for allelic heterogeneity may facilitate the discovery of novel genes not detectable by models that require replication of a single variant site. One strategy to accomplish this is to focus on genes rather than markers as units of association, and so potentially capture a spectrum of causal alleles that differ across populations. Here, we conducted a GWAS of Alzheimer disease (AD) in 2,586 Swedes and performed gene-based meta-analysis with three additional studies from France, Canada, and the United States, in total encompassing 4,259 cases and 8,284 controls. Implementing a newly designed gene-based algorithm, we identified two loci apart from the region around APOE that achieved study-wide significance in combined samples, the strongest finding being for FRMD6 on chromosome 14q (P = 2.6 × 10(-14)) and a weaker signal for NARS2 that is immediately adjacent to GAB2 on chromosome 11q (P = 7.8 × 10(-9)). Ontology-based pathway analyses revealed significant enrichment of genes involved in glycosylation. Results suggest that gene-based approaches that accommodate allelic heterogeneity in GWAS can provide a complementary avenue for gene discovery and may help to explain a portion of the missing heritability not detectable with single nucleotide polymorphisms (SNPs) derived from marker-specific meta-analysis. © 2011 Wiley Periodicals, Inc.

CARSVM: a class association rule-based classification framework and its application to gene expression data.

PubMed

Kianmehr, Keivan; Alhajj, Reda

2008-09-01

In this study, we aim at building a classification framework, namely the CARSVM model, which integrates association rule mining and support vector machine (SVM). The goal is to benefit from advantages of both, the discriminative knowledge represented by class association rules and the classification power of the SVM algorithm, to construct an efficient and accurate classifier model that improves the interpretability problem of SVM as a traditional machine learning technique and overcomes the efficiency issues of associative classification algorithms. In our proposed framework: instead of using the original training set, a set of rule-based feature vectors, which are generated based on the discriminative ability of class association rules over the training samples, are presented to the learning component of the SVM algorithm. We show that rule-based feature vectors present a high-qualified source of discrimination knowledge that can impact substantially the prediction power of SVM and associative classification techniques. They provide users with more conveniences in terms of understandability and interpretability as well. We have used four datasets from UCI ML repository to evaluate the performance of the developed system in comparison with five well-known existing classification methods. Because of the importance and popularity of gene expression analysis as real world application of the classification model, we present an extension of CARSVM combined with feature selection to be applied to gene expression data. Then, we describe how this combination will provide biologists with an efficient and understandable classifier model. The reported test results and their biological interpretation demonstrate the applicability, efficiency and effectiveness of the proposed model. From the results, it can be concluded that a considerable increase in classification accuracy can be obtained when the rule-based feature vectors are integrated in the learning process of the SVM algorithm. In the context of applicability, according to the results obtained from gene expression analysis, we can conclude that the CARSVM system can be utilized in a variety of real world applications with some adjustments.

The role of interpersonal communication in the process of knowledge mobilization within a community-based organization: a network analysis.

PubMed

Gainforth, Heather L; Latimer-Cheung, Amy E; Athanasopoulos, Peter; Moore, Spencer; Ginis, Kathleen A Martin

2014-05-22

Diffusion of innovations theory has been widely used to explain knowledge mobilization of research findings. This theory posits that individuals who are more interpersonally connected within an organization may be more likely to adopt an innovation (e.g., research evidence) than individuals who are less interconnected. Research examining this tenet of diffusion of innovations theory in the knowledge mobilization literature is limited. The purpose of the present study was to use network analysis to examine the role of interpersonal communication in the adoption and mobilization of the physical activity guidelines for people with spinal cord injury (SCI) among staff in a community-based organization (CBO). The study used a cross-sectional, whole-network design. In total, 56 staff completed the network survey. Adoption of the guidelines was assessed using Rogers' innovation-decision process and interpersonal communication was assessed using an online network instrument. The patterns of densities observed within the network were indicative of a core-periphery structure revealing that interpersonal communication was greater within the core than between the core and periphery and within the periphery. Membership in the core, as opposed to membership in the periphery, was associated with greater knowledge of the evidence-based physical activity resources available and engagement in physical activity promotion behaviours (ps < 0.05). Greater in-degree centrality was associated with adoption of evidence-based behaviours (p < 0.05). Findings suggest that interpersonal communication is associated with knowledge mobilization and highlight how the network structure could be improved for further dissemination efforts. diffusion of innovations; network analysis; community-based organization; knowledge mobilization; knowledge translation, interpersonal communication.

Is nutritional labeling associated with individual health? The effects of labeling-based awareness on dyslipidemia risk in a South Korean population.

PubMed

Kim, Jong Yeob; Kweon, Ki Hong; Kim, Min Jae; Park, Eun-Cheol; Jang, Suk-Yong; Kim, Woorim; Han, Kyu-Tae

2016-09-15

In 1995, the South Korean government made nutrition labeling compulsory, which has positively impacted patients with certain chronic diseases, such as dyslipidemia. We investigated the association between nutrition labeling-based awareness and the risk of dyslipidemia among individuals not yet diagnosed. Our study used data from the fifth Korea National Health and Nutrition Examination Surveys administered during 2010-2014 (n = 17,687). We performed multiple or logistic regression analysis to examine the association between nutritional analysis and various outcome variables. Approximately 70 % of the respondents (n = 11,513) were familiar with nutrition labeling, of which 20 % (n = 3172) decided what food to buy based on that information. This awareness yielded mostly positive results on outcome indicators, such as triglyceride and high-density lipoprotein cholesterol levels. In general, individuals who used nutritional labels to make decisions regarding food purchases had a lower risk of dyslipidemia than individuals who did not (OR: 0.806, 95 % CI: 0.709-0.917). Utilizing nutrition labels for making food choices correlated with a lower risk of dyslipidemia in certain subgroups. Based on our findings, we recommend that health policymakers and medical professionals consider promoting nutrition labeling as an alternative method for managing certain chronic diseases in South Korean patients.

A Risk Stratification Model for Lung Cancer Based on Gene Coexpression Network and Deep Learning

PubMed Central

2018-01-01

Risk stratification model for lung cancer with gene expression profile is of great interest. Instead of previous models based on individual prognostic genes, we aimed to develop a novel system-level risk stratification model for lung adenocarcinoma based on gene coexpression network. Using multiple microarray, gene coexpression network analysis was performed to identify survival-related networks. A deep learning based risk stratification model was constructed with representative genes of these networks. The model was validated in two test sets. Survival analysis was performed using the output of the model to evaluate whether it could predict patients' survival independent of clinicopathological variables. Five networks were significantly associated with patients' survival. Considering prognostic significance and representativeness, genes of the two survival-related networks were selected for input of the model. The output of the model was significantly associated with patients' survival in two test sets and training set (p < 0.00001, p < 0.0001 and p = 0.02 for training and test sets 1 and 2, resp.). In multivariate analyses, the model was associated with patients' prognosis independent of other clinicopathological features. Our study presents a new perspective on incorporating gene coexpression networks into the gene expression signature and clinical application of deep learning in genomic data science for prognosis prediction. PMID:29581968

Association of type 1 diabetes and concentrations of drinking water components in Newfoundland and Labrador, Canada.

PubMed

Chafe, Roger; Aslanov, Rana; Sarkar, Atanu; Gregory, Peter; Comeau, Alex; Newhook, Leigh Anne

2018-01-01

To determine the association between drinking water quality and rates of type 1 diabetes in the Newfoundland and Labrador (NL) population, which has one of the highest incidences of type 1 diabetes reported globally. The study used a community-based, case-control design. We first calculated incidence rates of type 1 diabetes at the provincial, regional and community levels. The connection between incidence rates and components in public water supplies were then analyzed in three ways: to evaluate differences in water quality between communities with and without incident cases of type 1 diabetes, and to analyze the relationship between water quality and incidence rates of type 1 diabetes at both the community and regional levels. The provincial incidence of type 1 diabetes was 51.7/100 000 (0-14 year age group) for the period studied. In the community-based analysis, there were significant associations found between higher concentrations of arsenic (β=0.268, P=0.013) and fluoride (β=0.202, P=0.005) in drinking water and higher incidence of type 1 diabetes. In the regional analysis, barium (β=-0.478, P=0.009) and nickel (β=-0.354, P=0.050) concentrations were negatively associated with incidence of type 1 diabetes. We confirmed the high incidence of type 1 diabetes in NL. We also found that concentrations of some components in drinking water were associated with higher incidence of type 1 diabetes, but no component was found to have a significant association across the three different levels of analysis performed.

Analysis of a Shock-Associated Noise Prediction Model Using Measured Jet Far-Field Noise Data

NASA Technical Reports Server (NTRS)

Dahl, Milo D.; Sharpe, Jacob A.

2014-01-01

A code for predicting supersonic jet broadband shock-associated noise was assessed using a database containing noise measurements of a jet issuing from a convergent nozzle. The jet was operated at 24 conditions covering six fully expanded Mach numbers with four total temperature ratios. To enable comparisons of the predicted shock-associated noise component spectra with data, the measured total jet noise spectra were separated into mixing noise and shock-associated noise component spectra. Comparisons between predicted and measured shock-associated noise component spectra were used to identify deficiencies in the prediction model. Proposed revisions to the model, based on a study of the overall sound pressure levels for the shock-associated noise component of the measured data, a sensitivity analysis of the model parameters with emphasis on the definition of the convection velocity parameter, and a least-squares fit of the predicted to the measured shock-associated noise component spectra, resulted in a new definition for the source strength spectrum in the model. An error analysis showed that the average error in the predicted spectra was reduced by as much as 3.5 dB for the revised model relative to the average error for the original model.

GWATCH: a web platform for automated gene association discovery analysis.

PubMed

Svitin, Anton; Malov, Sergey; Cherkasov, Nikolay; Geerts, Paul; Rotkevich, Mikhail; Dobrynin, Pavel; Shevchenko, Andrey; Guan, Li; Troyer, Jennifer; Hendrickson, Sher; Dilks, Holli Hutcheson; Oleksyk, Taras K; Donfield, Sharyne; Gomperts, Edward; Jabs, Douglas A; Sezgin, Efe; Van Natta, Mark; Harrigan, P Richard; Brumme, Zabrina L; O'Brien, Stephen J

2014-01-01

As genome-wide sequence analyses for complex human disease determinants are expanding, it is increasingly necessary to develop strategies to promote discovery and validation of potential disease-gene associations. Here we present a dynamic web-based platform - GWATCH - that automates and facilitates four steps in genetic epidemiological discovery: 1) Rapid gene association search and discovery analysis of large genome-wide datasets; 2) Expanded visual display of gene associations for genome-wide variants (SNPs, indels, CNVs), including Manhattan plots, 2D and 3D snapshots of any gene region, and a dynamic genome browser illustrating gene association chromosomal regions; 3) Real-time validation/replication of candidate or putative genes suggested from other sources, limiting Bonferroni genome-wide association study (GWAS) penalties; 4) Open data release and sharing by eliminating privacy constraints (The National Human Genome Research Institute (NHGRI) Institutional Review Board (IRB), informed consent, The Health Insurance Portability and Accountability Act (HIPAA) of 1996 etc.) on unabridged results, which allows for open access comparative and meta-analysis. GWATCH is suitable for both GWAS and whole genome sequence association datasets. We illustrate the utility of GWATCH with three large genome-wide association studies for HIV-AIDS resistance genes screened in large multicenter cohorts; however, association datasets from any study can be uploaded and analyzed by GWATCH.

Use of benzodiazepine and risk of cancer: A meta-analysis of observational studies.

PubMed

Kim, Hong-Bae; Myung, Seung-Kwon; Park, Yon Chul; Park, Byoungjin

2017-02-01

Several observational epidemiological studies have reported inconsistent results on the association between the use of benzodiazepine and the risk of cancer. We investigated the association by using a meta-analysis. We searched PubMed, EMBASE, and the bibliographies of relevant articles to locate additional publications in January 2016. Three evaluators independently reviewed and selected eligible studies based on predetermined selection criteria. Of 796 articles meeting our initial criteria, a total of 22 observational epidemiological studies with 18 case-control studies and 4 cohort studies were included in the final analysis. Benzodiazepine use was significantly associated with an increased risk of cancer (odds ratio [OR] or relative risk [RR] 1.19; 95% confidence interval 1.16-1.21) in a random-effects meta-analysis of all studies. Subgroup meta-analyses by various factors such as study design, type of case-control study, study region, and methodological quality of study showed consistent findings. Also, a significant dose-response relationship was observed between the use of benzodiazepine and the risk of cancer (p for trend <0.01). The current meta-analysis of observational epidemiological studies suggests that benzodiazepine use is associated with an increased risk of cancer. © 2016 UICC.

Prediction of future falls in a community dwelling older adult population using instrumented balance and gait analysis.

PubMed

Bauer, C M; Gröger, I; Rupprecht, R; Marcar, V L; Gaßmann, K G

2016-04-01

The role of instrumented balance and gait assessment when screening for prospective fallers is currently a topic of controversial discussion. This study analyzed the association between variables derived from static posturography, instrumented gait analysis and clinical assessments with the occurrence of prospective falls in a sample of community dwelling older people. In this study 84 older people were analyzed. Based on a prospective occurrence of falls, participants were categorized into fallers and non-fallers. Variables derived from clinical assessments, static posturography and instrumented gait analysis were evaluated with respect to the association with the occurrence of prospective falls using a forward stepwise, binary, logistic regression procedure. Fallers displayed a significantly shorter single support time during walking while counting backwards, increased mediolateral to anteroposterior sway amplitude ratio, increased fast mediolateral oscillations and a larger coefficient (Coeff) of sway direction during various static posturography tests. Previous falls were insignificantly associated with the occurrence of prospective falls. Variables derived from posturography and instrumented gait analysis showed significant associations with the occurrence of prospective falls in a sample of community dwelling older adults.

Leadership, Organizational Climate, and Perceived Burden of Evidence-Based Practice in Mental Health Services.

PubMed

Brimhall, Kim C; Fenwick, Karissa; Farahnak, Lauren R; Hurlburt, Michael S; Roesch, Scott C; Aarons, Gregory A

2016-09-01

The use of evidence-based practices (EBPs) is associated with favorable client outcomes, yet perceived burden of using EBPs may affect the adoption and implementation of such practices. Multilevel path analysis was used to examine the associations of transformational leadership with organizational climate, and their associations with perceived burden of using EBPs. Results indicated significant relationships between transformational leadership and empowering and demoralizing climates, and between demoralizing climate and perceived burden of EBPs. We found significant indirect associations of leadership and perceived burden through organizational climate. Findings suggest that further research is needed to examine the extent to which improving leadership and organizational climate may reduce perceived burden and use of EBPs with the ultimate goal of enhancing quality of care.

Analysis of polarized-light effects in glass-promoting solutions with applications to cryopreservation and organ banking.

PubMed

Solanki, Prem K; Rabin, Yoed

2018-01-01

This study presents experimental results and an analysis approach for polarized light effects associated with thermomechanical stress during cooling of glass promoting solutions, with applications to cryopreservation and tissue banking in a process known as vitrification. Polarized light means have been previously integrated into the cryomacroscope-a visualization device to detect physical effects associated with cryopreservation success, such as crystallization, fracture formation, and contamination. The experimental study concerns vitrification in a cuvette, which is a rectangular container. Polarized light modeling in the cuvette is based on subdividing the tridimensional (3D) domain into a series of planar (2D) problems, for which a mathematical solution is available in the literature. The current analysis is based on tracking the accumulated changes in light polarization and magnitude, as it passes through the sequence of planar problems. Results of this study show qualitative agreement in light intensity history and distribution between experimental data and simulated results. The simulated results help explaining differences between 2D and 3D effects in photoelasticity, most notably, the counterintuitive observation that high stress areas may correlate with low light intensity regions based on the particular experimental conditions. Finally, it is suggested that polarized-light analysis must always be accompanied by thermomechanical stress modeling in order to explain 3D effects.

Analysis of polarized-light effects in glass-promoting solutions with applications to cryopreservation and organ banking

PubMed Central

2018-01-01

This study presents experimental results and an analysis approach for polarized light effects associated with thermomechanical stress during cooling of glass promoting solutions, with applications to cryopreservation and tissue banking in a process known as vitrification. Polarized light means have been previously integrated into the cryomacroscope—a visualization device to detect physical effects associated with cryopreservation success, such as crystallization, fracture formation, and contamination. The experimental study concerns vitrification in a cuvette, which is a rectangular container. Polarized light modeling in the cuvette is based on subdividing the tridimensional (3D) domain into a series of planar (2D) problems, for which a mathematical solution is available in the literature. The current analysis is based on tracking the accumulated changes in light polarization and magnitude, as it passes through the sequence of planar problems. Results of this study show qualitative agreement in light intensity history and distribution between experimental data and simulated results. The simulated results help explaining differences between 2D and 3D effects in photoelasticity, most notably, the counterintuitive observation that high stress areas may correlate with low light intensity regions based on the particular experimental conditions. Finally, it is suggested that polarized-light analysis must always be accompanied by thermomechanical stress modeling in order to explain 3D effects. PMID:29912973

Comparative Analysis of Metabolic Syndrome Components in over 15,000 African Americans Identifies Pleiotropic Variants: Results from the PAGE Study

PubMed Central

Carty, Cara L.; Bhattacharjee, Samsiddhi; Haessler, Jeff; Cheng, Iona; Hindorff, Lucia A.; Aroda, Vanita; Carlson, Christopher S.; Hsu, Chun-Nan; Wilkens, Lynne; Liu, Simin; Selvin, Elizabeth; Jackson, Rebecca; North, Kari E.; Peters, Ulrike; Pankow, James S.; Chatterjee, Nilanjan; Kooperberg, Charles

2014-01-01

Background Metabolic syndrome (MetS) refers to the clustering of cardio-metabolic risk factors including dyslipidemia, central adiposity, hypertension and hyperglycemia in individuals. Identification of pleiotropic genetic factors associated with MetS traits may shed light on key pathways or mediators underlying MetS. Methods and Results Using the Metabochip array in 15,148 African Americans (AA) from the PAGE Study, we identify susceptibility loci and investigate pleiotropy among genetic variants using a subset-based meta-analysis method, ASsociation-analysis-based-on-subSETs (ASSET). Unlike conventional models which lack power when associations for MetS components are null or have opposite effects, ASSET uses one-sided tests to detect positive and negative associations for components separately and combines tests accounting for correlations among components. With ASSET, we identify 27 SNPs in 1 glucose and 4 lipids loci (TCF7L2, LPL, APOA5, CETP, LPL, APOC1/APOE/TOMM40) significantly associated with MetS components overall, all P< 2.5e-7, the Bonferroni adjusted P-value. Three loci replicate in a Hispanic population, n=5172. A novel AA-specific variant, rs12721054/APOC1, and rs10096633/LPL are associated with ≥3 MetS components. We find additional evidence of pleiotropy for APOE, TOMM40, TCF7L2 and CETP variants, many with opposing effects; e.g. the same rs7901695/TCF7L2 allele is associated with increased odds of high glucose and decreased odds of central adiposity. Conclusions We highlight a method to increase power in large-scale genomic association analyses, and report a novel variant associated with all MetS components in AA. We also identify pleiotropic associations that may be clinically useful in patient risk profiling and for informing translational research of potential gene targets and medications. PMID:25023634

Differential Adverse Event Profiles Associated with BCG as a Preventive Tuberculosis Vaccine or Therapeutic Bladder Cancer Vaccine Identified by Comparative Ontology-Based VAERS and Literature Meta-Analysis

PubMed Central

Xie, Jiangan; Codd, Christopher; Mo, Kevin; He, Yongqun

2016-01-01

M. bovis strain Bacillus Calmette–Guérin (BCG) has been the only licensed live attenuated vaccine against tuberculosis (TB) for nearly one century and has also been approved as a therapeutic vaccine for bladder cancer treatment since 1990. During its long time usage, different adverse events (AEs) have been reported. However, the AEs associated with the BCG preventive TB vaccine and therapeutic cancer vaccine have not been systematically compared. In this study, we systematically collected various BCG AE data mined from the US VAERS database and PubMed literature reports, identified statistically significant BCG-associated AEs, and ontologically classified and compared these AEs related to these two types of BCG vaccine. From 397 VAERS BCG AE case reports, we identified 64 AEs statistically significantly associated with the BCG TB vaccine and 14 AEs with the BCG cancer vaccine. Our meta-analysis of 41 peer-reviewed journal reports identified 48 AEs associated with the BCG TB vaccine and 43 AEs associated with the BCG cancer vaccine. Among all identified AEs from VAERS and literature reports, 25 AEs belong to serious AEs. The Ontology of Adverse Events (OAE)-based ontological hierarchical analysis indicated that the AEs associated with the BCG TB vaccine were enriched in immune system (e.g., lymphadenopathy and lymphadenitis), skin (e.g., skin ulceration and cyanosis), and respiratory system (e.g., cough and pneumonia); in contrast, the AEs associated with the BCG cancer vaccine mainly occurred in the urinary system (e.g., dysuria, pollakiuria, and hematuria). With these distinct AE profiles detected, this study also discovered three AEs (i.e., chills, pneumonia, and C-reactive protein increased) shared by the BCG TB vaccine and bladder cancer vaccine. Furthermore, our deep investigation of 24 BCG-associated death cases from VAERS identified the important effects of age, vaccine co-administration, and immunosuppressive status on the final BCG-associated death outcome. PMID:27749923

Genome-Wide Association Analysis Identifies Variants Associated with Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits

PubMed Central

Palmer, Cameron D.; Gudnason, Vilmundur; Eiriksdottir, Gudny; Garcia, Melissa E.; Launer, Lenore J.; Nalls, Michael A.; Clark, Jeanne M.; Mitchell, Braxton D.; Shuldiner, Alan R.; Butler, Johannah L.; Tomas, Marta; Hoffmann, Udo; Hwang, Shih-Jen; Massaro, Joseph M.; O'Donnell, Christopher J.; Sahani, Dushyant V.; Salomaa, Veikko; Schadt, Eric E.; Schwartz, Stephen M.; Siscovick, David S.; Voight, Benjamin F.; Carr, J. Jeffrey; Feitosa, Mary F.; Harris, Tamara B.; Fox, Caroline S.

2011-01-01

Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%–27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10−8) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT–assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits. PMID:21423719

Development of a Aerothermoelastic-Acoustics Simulation Capability of Flight Vehicles

NASA Technical Reports Server (NTRS)

Gupta, K. K.; Choi, S. B.; Ibrahim, A.

2010-01-01

A novel numerical, finite element based analysis methodology is presented in this paper suitable for accurate and efficient simulation of practical, complex flight vehicles. An associated computer code, developed in this connection, is also described in some detail. Thermal effects of high speed flow obtained from a heat conduction analysis are incorporated in the modal analysis which in turn affects the unsteady flow arising out of interaction of elastic structures with the air. Numerical examples pertaining to representative problems are given in much detail testifying to the efficacy of the advocated techniques. This is a unique implementation of temperature effects in a finite element CFD based multidisciplinary simulation analysis capability involving large scale computations.

Rapid increase in Japanese life expectancy after World War II.

PubMed

Sugiura, Yasuo; Ju, Young-Su; Yasuoka, Junko; Jimba, Masamine

2010-02-01

Japanese life expectancy increased by about 13.7 years during the first decade after World War II, despite the country's post-war poverty. Although it is known that medical progress explains part of this increase, roles of non-medical factors have not been systematically studied. This study hypothesizes that non-medical factors, in addition to medical factors, are associated with the rapid increase in life expectancy in Japan. We analyzed the time trends of potential explanatory factors and used regression analysis with historical data from the Ministry of Internal Affairs and Communications' Historical Statistics of Japan during the period between 1946 and 1983. Time trends analysis revealed that the rapid increase in life expectancy preceded the dramatic growth of per capita Gross Domestic Product (GDP) by 10 years. In education, the nearly universal enrollment in elementary schools and increased advancement to upper secondary schools for both sexes were associated with better health. Regarding legislation, 32 health laws were passed in the first decade after the war and these laws were associated with improved health. Using regression analysis, we found that the enrollment rate in elementary schools, the number of health laws, and expansion of community-based activity staff were significantly associated with the increased life expectancy during the first decade after World War II. To conclude, in addition to medical factors, non-medical factors applied across the country, particularly education, community-based activities and legislation were associated with the rapid increase in Japanese life expectancy after World War II.

Is there an association between bruxism and intestinal parasitic infestation in children?

PubMed

Díaz-Serrano, Kranya Victoria; da Silva, Carolina Brunelli Alvares; de Albuquerque, Sérgio; Pereira Saraiva, Maria da Conceição; Nelson-Filho, Paulo

2008-01-01

Multiple factors have been considered in the etiology of bruxism in pediatric patients, among which are infestations by intestinal parasites suggested by some authors. No empirical evidence exists, however, of such association. Therefore, this study's purpose was to investigate the existence of an association between bruxism and intestinal parasitic infestation in children. Fifty-seven 6- to 11-year-olds (30 cases and 27 controls) who had not used anthelminthics 2 months before the baseline examination were enrolled in the study. A diagnosis of bruxism was based on an intraoral clinical examination performed by a single trained examiner and on the parent/guardian's report of any perceived parafunctional habits (questionnaire-based interview). Bruxism cases were defined as those children with a report of currently perceived habits of eccentric or centric bruxism (tooth-grinding and tooth-clenching, respectively) combined with clinical evidence of nonphysiologic wear facets. The volunteers were required to collect 3 fecal samples (1 every 2 to 3 days). Parasitologic analysis was performed using the spontaneous sedimentation method. Data gathered from the intraoral clinical examination, questionnaire, and parasitologic analysis were tabulated and submitted to statistical analysis using the chi-square test and student's t test. Intestinal parasitic infestation was observed in 30% (N=9) of cases and 41% (N=11) of controls, but no statistically significant association was observed (P=.40). This study's findings do not support the existence of an association between intestinal parasitic infestation and bruxism among the evaluated pediatric population.

Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence.

PubMed

Sniekers, Suzanne; Stringer, Sven; Watanabe, Kyoko; Jansen, Philip R; Coleman, Jonathan R I; Krapohl, Eva; Taskesen, Erdogan; Hammerschlag, Anke R; Okbay, Aysu; Zabaneh, Delilah; Amin, Najaf; Breen, Gerome; Cesarini, David; Chabris, Christopher F; Iacono, William G; Ikram, M Arfan; Johannesson, Magnus; Koellinger, Philipp; Lee, James J; Magnusson, Patrik K E; McGue, Matt; Miller, Mike B; Ollier, William E R; Payton, Antony; Pendleton, Neil; Plomin, Robert; Rietveld, Cornelius A; Tiemeier, Henning; van Duijn, Cornelia M; Posthuma, Danielle

2017-07-01

Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10 -8 ) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10 -6 ), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10 -6 ). Despite the well-known difference in twin-based heritability for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (r g = 0.89, LD score regression P = 5.4 × 10 -29 ). These findings provide new insight into the genetic architecture of intelligence.

Specific Transcriptome Changes Associated with Blood Pressure Reduction in Hypertensive Patients After Relaxation Response Training.

PubMed

Bhasin, Manoj K; Denninger, John W; Huffman, Jeff C; Joseph, Marie G; Niles, Halsey; Chad-Friedman, Emma; Goldman, Roberta; Buczynski-Kelley, Beverly; Mahoney, Barbara A; Fricchione, Gregory L; Dusek, Jeffery A; Benson, Herbert; Zusman, Randall M; Libermann, Towia A

2018-05-01

Mind-body practices that elicit the relaxation response (RR) have been demonstrated to reduce blood pressure (BP) in essential hypertension (HTN) and may be an adjunct to antihypertensive drug therapy. However, the molecular mechanisms by which the RR reduces BP remain undefined. Genomic determinants associated with responsiveness to an 8-week RR-based mind-body intervention for lowering HTN in 13 stage 1 hypertensive patients classified as BP responders and 11 as nonresponders were identified. Transcriptome analysis in peripheral blood mononuclear cells identified 1771 genes regulated by the RR in responders. Biological process- and pathway-based analysis of transcriptome data demonstrated enrichment in the following gene categories: immune regulatory pathways and metabolism (among downregulated genes); glucose metabolism, cardiovascular system development, and circadian rhythm (among upregulated genes). Further in silico estimation of cell abundance from the microarray data showed enrichment of the anti-inflammatory M2 subtype of macrophages in BP responders. Nuclear factor-κB, vascular endothelial growth factor, and insulin were critical molecules emerging from interactive network analysis. These findings provide the first insights into the molecular mechanisms that are associated with the beneficial effects of the RR on HTN.

Specific Transcriptome Changes Associated with Blood Pressure Reduction in Hypertensive Patients After Relaxation Response Training

PubMed Central

Bhasin, Manoj K.; Denninger, John W.; Huffman, Jeff C.; Joseph, Marie G.; Niles, Halsey; Chad-Friedman, Emma; Goldman, Roberta; Buczynski-Kelley, Beverly; Mahoney, Barbara A.; Fricchione, Gregory L.; Dusek, Jeffery A.; Benson, Herbert; Zusman, Randall M.

2018-01-01

Abstract Objective: Mind–body practices that elicit the relaxation response (RR) have been demonstrated to reduce blood pressure (BP) in essential hypertension (HTN) and may be an adjunct to antihypertensive drug therapy. However, the molecular mechanisms by which the RR reduces BP remain undefined. Design: Genomic determinants associated with responsiveness to an 8-week RR-based mind–body intervention for lowering HTN in 13 stage 1 hypertensive patients classified as BP responders and 11 as nonresponders were identified. Results: Transcriptome analysis in peripheral blood mononuclear cells identified 1771 genes regulated by the RR in responders. Biological process- and pathway-based analysis of transcriptome data demonstrated enrichment in the following gene categories: immune regulatory pathways and metabolism (among downregulated genes); glucose metabolism, cardiovascular system development, and circadian rhythm (among upregulated genes). Further in silico estimation of cell abundance from the microarray data showed enrichment of the anti-inflammatory M2 subtype of macrophages in BP responders. Nuclear factor-κB, vascular endothelial growth factor, and insulin were critical molecules emerging from interactive network analysis. Conclusions: These findings provide the first insights into the molecular mechanisms that are associated with the beneficial effects of the RR on HTN. PMID:29616846

Agricultural Adaptation to Climate Change

NASA Astrophysics Data System (ADS)

Tam, A.; Jain, M.

2016-12-01

This research includes two projects pertaining to agricultural systems' adaption to climate change. The first research project focuses on the wheat yielding regions of India. Wheat is a major staple crop and many rural households and smallholder farmers rely on crop yields for survival. We examine the impacts of weather variability and groundwater depletion on agricultural systems, using geospatial analysis and satellite-based analysis and household-based and census data sets. We use these methods to estimate the crop yields and identify what factors are associated with low versus high yielding regions. This can help identify strategies that should be further promoted to increase crop yields. The second research project is a literature review. We conduct a meta-analysis and synthetic review on literature about agricultural adaptation to climate change. We sort through numerous articles to identify and examine articles that associate socio-economic, biophysical, and perceptional factors to farmers' adaption to climate change. Our preliminary results show that researchers tend to associate few factors to a farmers' vulnerability and adaptive capacity, and most of the research conducted is concentrated in North America, whereas tropical regions that are highly vulnerable to weather variability are underrepresented by literature. There are no conclusive results in both research projects as of so far.

Prognostic value of inflammation-based scores in patients with osteosarcoma

PubMed Central

Liu, Bangjian; Huang, Yujing; Sun, Yuanjue; Zhang, Jianjun; Yao, Yang; Shen, Zan; Xiang, Dongxi; He, Aina

2016-01-01

Systemic inflammation responses have been associated with cancer development and progression. C-reactive protein (CRP), Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and neutrophil-platelet score (NPS) have been shown to be independent risk factors in various types of malignant tumors. This retrospective analysis of 162 osteosarcoma cases was performed to estimate their predictive value of survival in osteosarcoma. All statistical analyses were performed by SPSS statistical software. Receiver operating characteristic (ROC) analysis was generated to set optimal thresholds; area under the curve (AUC) was used to show the discriminatory abilities of inflammation-based scores; Kaplan-Meier analysis was performed to plot the survival curve; cox regression models were employed to determine the independent prognostic factors. The optimal cut-off points of NLR, PLR, and LMR were 2.57, 123.5 and 4.73, respectively. GPS and NLR had a markedly larger AUC than CRP, PLR and LMR. High levels of CRP, GPS, NLR, PLR, and low level of LMR were significantly associated with adverse prognosis (P < 0.05). Multivariate Cox regression analyses revealed that GPS, NLR, and occurrence of metastasis were top risk factors associated with death of osteosarcoma patients. PMID:28008988

A Stochastic Multi-Attribute Assessment of Energy Options for Fairbanks, Alaska

NASA Astrophysics Data System (ADS)

Read, L.; Madani, K.; Mokhtari, S.; Hanks, C. L.; Sheets, B.

2012-12-01

Many competing projects have been proposed to address Interior Alaska's high cost of energy—both for electricity production and for heating. Public and private stakeholders are considering the costs associated with these competing projects which vary in fuel source, subsidy requirements, proximity, and other factors. As a result, the current projects under consideration involve a complex cost structure of potential subsidies and reliance on present and future market prices, introducing a significant amount of uncertainty associated with each selection. Multi-criteria multi-decision making (MCMDM) problems of this nature can benefit from game theory and systems engineering methods, which account for behavior and preferences of stakeholders in the analysis to produce feasible and relevant solutions. This work uses a stochastic MCMDM framework to evaluate the trade-offs of each proposed project based on a complete cost analysis, environmental impact, and long-term sustainability. Uncertainty in the model is quantified via a Monte Carlo analysis, which helps characterize the sensitivity and risk associated with each project. Based on performance measures and criteria outlined by the stakeholders, a decision matrix will inform policy on selecting a project that is both efficient and preferred by the constituents.

Association between lipoprotein(a) level and type 2 diabetes: no evidence for a causal role of lipoprotein(a) and insulin.

PubMed

Buchmann, Nikolaus; Scholz, Markus; Lill, Christina M; Burkhardt, Ralph; Eckardt, Rahel; Norman, Kristina; Loeffler, Markus; Bertram, Lars; Thiery, Joachim; Steinhagen-Thiessen, Elisabeth; Demuth, Ilja

2017-11-01

Inverse relationships have been described between the largely genetically determined levels of serum/plasma lipoprotein(a) [Lp(a)], type 2 diabetes (T2D) and fasting insulin. Here, we aimed to evaluate the nature of these relationships with respect to causality. We tested whether we could replicate the recent negative findings on causality between Lp(a) and T2D by employing the Mendelian randomization (MR) approach using cross-sectional data from three independent cohorts, Berlin Aging Study II (BASE-II; n = 2012), LIFE-Adult (n = 3281) and LIFE-Heart (n = 2816). Next, we explored another frequently discussed hypothesis in this context: Increasing insulin levels during the course of T2D disease development inhibits hepatic Lp(a) synthesis and thereby might explain the inverse Lp(a)-T2D association. We used two fasting insulin-associated variants, rs780094 and rs10195252, as instrumental variables in MR analysis of n = 4937 individuals from BASE-II and LIFE-Adult. We further investigated causality of the association between fasting insulin and Lp(a) by combined MR analysis of 12 additional SNPs in LIFE-Adult. While an Lp(a)-T2D association was observed in the combined analysis (meta-effect of OR [95% CI] = 0.91 [0.87-0.96] per quintile, p = 1.3x10 -4 ), we found no evidence of causality in the Lp(a)-T2D association (p = 0.29, fixed effect model) when using the variant rs10455872 as the instrumental variable in the MR analyses. Likewise, no evidence of a causal effect of insulin on Lp(a) levels was found. While these results await confirmation in larger cohorts, the nature of the inverse Lp(a)-T2D association remains to be elucidated.

Network-based integration of GWAS and gene expression identifies a HOX-centric network associated with serous ovarian cancer risk

PubMed Central

Kar, Siddhartha P.; Tyrer, Jonathan P.; Li, Qiyuan; Lawrenson, Kate; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Chenevix-Trench, Georgia; Baker, Helen; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Berchuck, Andrew; Bisogna, Maria; Bjørge, Line; Bogdanova, Natalia; Brinton, Louise; Brooks-Wilson, Angela; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Chen, Yian Ann; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas F.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goode, Ellen L.; Goodman, Marc T.; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus K.; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Paul, James; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kjaer, Susanne K.; Kelemen, Linda E.; Kellar, Melissa; Kelley, Joseph; Kiemeney, Lambertus A.; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain A.; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Phelan, Catherine M.; Pike, Malcolm C.; Poole, Elizabeth M.; Ramus, Susan J.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schildkraut, Joellen M.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston-Campbell, Lara E.; Tangen, Ingvild L.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S.; van Altena, Anne M.; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A.; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A.; Monteiro, Alvaro N. A.; Freedman, Matthew L.; Gayther, Simon A.; Pharoah, Paul D. P.

2015-01-01

Background Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by co-expression may also be enriched for additional EOC risk associations. Methods We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly co-expressed with each selected TF gene in the unified microarray data set of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this data set were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). Results Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P<0.05 and FDR<0.05). These results were replicated (P<0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. Conclusion We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Impact Network analysis integrating large, context-specific data sets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. PMID:26209509

Nonlinear reduction in risk for colorectal cancer by fruit and vegetable intake based on meta-analysis of prospective studies.

PubMed

Aune, Dagfinn; Lau, Rosa; Chan, Doris S M; Vieira, Rui; Greenwood, Darren C; Kampman, Ellen; Norat, Teresa

2011-07-01

The association between fruit and vegetable intake and colorectal cancer risk has been investigated by many studies but is controversial because of inconsistent results and weak observed associations. We summarized the evidence from cohort studies in categorical, linear, and nonlinear, dose-response meta-analyses. We searched PubMed for studies of fruit and vegetable intake and colorectal cancer risk that were published until the end of May 2010. We included 19 prospective studies that reported relative risk estimates and 95% confidence intervals (CIs) of colorectal cancer-associated with fruit and vegetable intake. Random effects models were used to estimate summary relative risks. The summary relative risk for the highest vs the lowest intake was 0.92 (95% CI: 0.86-0.99) for fruit and vegetables combined, 0.90 (95% CI: 0.83-0.98) for fruit, and 0.91 (95% CI: 0.86-0.96) for vegetables (P for heterogeneity=.24, .05, and .54, respectively). The inverse associations appeared to be restricted to colon cancer. In linear dose-response analysis, only intake of vegetables was significantly associated with colorectal cancer risk (summary relative risk=0.98; 95% CI: 0.97-0.99), per 100 g/d. However, significant inverse associations emerged in nonlinear models for fruits (Pnonlinearity<.001) and vegetables (Pnonlinearity=.001). The greatest risk reduction was observed when intake increased from very low levels of intake. There was generally little evidence of heterogeneity in the analyses and there was no evidence of small-study bias. Based on meta-analysis of prospective studies, there is a weak but statistically significant nonlinear inverse association between fruit and vegetable intake and colorectal cancer risk. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

MSH3 rs26279 polymorphism increases cancer risk: a meta-analysis

PubMed Central

Miao, Hui-Kai; Chen, Li-Ping; Cai, Dong-Ping; Kong, Wei-Ju; Xiao, Li; Lin, Jie

2015-01-01

Previous studies have investigated the association of mutS homolog 3 (MSH3) rs26279 G > A polymorphism with the risk of different types of cancers including colorectal cancer, breast cancer, prostate cancer, bladder cancer, thyroid cancer, ovarian cancer and oesophageal cancer. However, its association with cancer remains conflicting. We performed a comprehensive meta-analysis to derive a more precise estimation of the relationship between MSH3 rs26279 G > A polymorphism and cancer susceptibility. Systematically searching the PubMed and EMBASE databases yielded 11 publications with 12 studies of 3282 cases and 6476 controls. The strength of the association was determined by crude odds ratios (OR) and 95% confidence intervals (CI). Overall, pooled risk estimates demonstrated that MSH3 rs26279 G > A was significantly associated with an increased overall cancer risk under all the genetic models (GG vs. AA: OR = 1.27, 95% CI = 1.09-1.48, P = 0.002; AG vs. AA: OR = 1.10, 95% CI = 1.00-1.21, P = 0.045; GG vs. AG + AA: OR = 1.23, 95% CI = 1.06-1.42, P = 0.005; AG + GG vs. AA: OR = 1.13, 95% CI = 1.04-1.24, P = 0.006; G vs. A: OR = 1.13, 95% CI = 1.05-1.20, P = 0.001). The association was more evident for colorectal cancer and breast cancer. Moreover, the significant association was also observed in the following subgroups: Europeans, Asians, population-based studies, hospital-based studies, and studies comprising relatively large sample size (≥ 200). Our meta-analysis results demonstrated that MSH3 rs26279 G > A polymorphism is associated with an increased risk of overall cancer, especially for the colorectal cancer and breast cancer. PMID:26617824

MSH3 rs26279 polymorphism increases cancer risk: a meta-analysis.

PubMed

Miao, Hui-Kai; Chen, Li-Ping; Cai, Dong-Ping; Kong, Wei-Ju; Xiao, Li; Lin, Jie

2015-01-01

Previous studies have investigated the association of mutS homolog 3 (MSH3) rs26279 G > A polymorphism with the risk of different types of cancers including colorectal cancer, breast cancer, prostate cancer, bladder cancer, thyroid cancer, ovarian cancer and oesophageal cancer. However, its association with cancer remains conflicting. We performed a comprehensive meta-analysis to derive a more precise estimation of the relationship between MSH3 rs26279 G > A polymorphism and cancer susceptibility. Systematically searching the PubMed and EMBASE databases yielded 11 publications with 12 studies of 3282 cases and 6476 controls. The strength of the association was determined by crude odds ratios (OR) and 95% confidence intervals (CI). Overall, pooled risk estimates demonstrated that MSH3 rs26279 G > A was significantly associated with an increased overall cancer risk under all the genetic models (GG vs. AA: OR = 1.27, 95% CI = 1.09-1.48, P = 0.002; AG vs. AA: OR = 1.10, 95% CI = 1.00-1.21, P = 0.045; GG vs. AG + AA: OR = 1.23, 95% CI = 1.06-1.42, P = 0.005; AG + GG vs. AA: OR = 1.13, 95% CI = 1.04-1.24, P = 0.006; G vs. A: OR = 1.13, 95% CI = 1.05-1.20, P = 0.001). The association was more evident for colorectal cancer and breast cancer. Moreover, the significant association was also observed in the following subgroups: Europeans, Asians, population-based studies, hospital-based studies, and studies comprising relatively large sample size (≥ 200). Our meta-analysis results demonstrated that MSH3 rs26279 G > A polymorphism is associated with an increased risk of overall cancer, especially for the colorectal cancer and breast cancer.

Association between fruit juice consumption and self-reported body mass index among adult Canadians.

PubMed

Akhtar-Danesh, N; Dehghan, M

2010-04-01

The prevalence of obesity and being overweight is rising among adult Canadians and diet is recognised as one of the main causes of obesity. The consumption of fruit and vegetables is shown to be protective against obesity and being overweight but little is known about the association of fruit juice consumption and obesity and being overweight. The present study aimed to investigate the association between fruit juice consumption and self-reported body mass index (BMI) among adult Canadians. This analysis is based on the Canadian Community Health Survey, Cycle 3.1. A regression method was used to assess the association of fruit juice consumption with self-reported BMI in 18-64-year-old Canadians who had been adjusted for sex, age, total household income, education, self-rated health, and daily energy expenditure. Because the analysis is based on a cross-sectional dataset, it does not imply a cause and effect relationship. Almost 38.6% of adult Canadians reported a fruit juice intake of 0.5-1.4 times per day and 18.2% consumed fruit juice more than 1.5 times per day. Participants with normal weight were likely to consume more fruit juice than obese individuals. Regression analysis showed a negative association between fruit juice consumption and BMI after adjusting for age, sex, education, marital status, income, total fruit and vegetable intake, daily energy expenditure, and self-rated health. On average, for each daily serving of fruit juice, a -0.22 unit (95% confidence interval = -0.33 to -0.11) decrease in BMI was observed. The results obtained showed a moderate negative association between fruit juice intake and BMI, which may suggest that a moderate daily consumption of fruit juice is associated with normal weight status.

Detection of EEG-patterns associated with real and imaginary movements using detrended fluctuation analysis

NASA Astrophysics Data System (ADS)

Pavlov, Alexey N.; Runnova, Anastasiya E.; Maksimenko, Vladimir A.; Grishina, Daria S.; Hramov, Alexander E.

2018-02-01

Authentic recognition of specific patterns of electroencephalograms (EEGs) associated with real and imagi- nary movements is an important stage for the development of brain-computer interfaces. In experiments with untrained participants, the ability to detect the motor-related brain activity based on the multichannel EEG processing is demonstrated. Using the detrended fluctuation analysis, changes in the EEG patterns during the imagination of hand movements are reported. It is discussed how the ability to recognize brain activity related to motor executions depends on the electrode position.

Tract-Based Spatial Statistics in Preterm-Born Neonates Predicts Cognitive and Motor Outcomes at 18 Months.

PubMed

Duerden, E G; Foong, J; Chau, V; Branson, H; Poskitt, K J; Grunau, R E; Synnes, A; Zwicker, J G; Miller, S P

2015-08-01

Adverse neurodevelopmental outcome is common in children born preterm. Early sensitive predictors of neurodevelopmental outcome such as MR imaging are needed. Tract-based spatial statistics, a diffusion MR imaging analysis method, performed at term-equivalent age (40 weeks) is a promising predictor of neurodevelopmental outcomes in children born very preterm. We sought to determine the association of tract-based spatial statistics findings before term-equivalent age with neurodevelopmental outcome at 18-months corrected age. Of 180 neonates (born at 24-32-weeks' gestation) enrolled, 153 had DTI acquired early at 32 weeks' postmenstrual age and 105 had DTI acquired later at 39.6 weeks' postmenstrual age. Voxelwise statistics were calculated by performing tract-based spatial statistics on DTI that was aligned to age-appropriate templates. At 18-month corrected age, 166 neonates underwent neurodevelopmental assessment by using the Bayley Scales of Infant Development, 3rd ed, and the Peabody Developmental Motor Scales, 2nd ed. Tract-based spatial statistics analysis applied to early-acquired scans (postmenstrual age of 30-33 weeks) indicated a limited significant positive association between motor skills and axial diffusivity and radial diffusivity values in the corpus callosum, internal and external/extreme capsules, and midbrain (P < .05, corrected). In contrast, for term scans (postmenstrual age of 37-41 weeks), tract-based spatial statistics analysis showed a significant relationship between both motor and cognitive scores with fractional anisotropy in the corpus callosum and corticospinal tracts (P < .05, corrected). Tract-based spatial statistics in a limited subset of neonates (n = 22) scanned at <30 weeks did not significantly predict neurodevelopmental outcomes. The strength of the association between fractional anisotropy values and neurodevelopmental outcome scores increased from early-to-late-acquired scans in preterm-born neonates, consistent with brain dysmaturation in this population. © 2015 by American Journal of Neuroradiology.

Application of gas chromatography to analysis of spirit-based alcoholic beverages.

PubMed

Wiśniewska, Paulina; Śliwińska, Magdalena; Dymerski, Tomasz; Wardencki, Waldemar; Namieśnik, Jacek

2015-01-01

Spirit-based beverages are alcoholic drinks; their production processes are dependent on the type and origin of raw materials. The composition of this complex matrix is difficult to analyze, and scientists commonly choose gas chromatography techniques for this reason. With a wide selection of extraction methods and detectors it is possible to provide qualitative and quantitative analysis for many chemical compounds with various functional groups. This article describes different types of gas chromatography techniques and their most commonly used associated extraction techniques (e.g., LLE, SPME, SPE, SFE, and SBME) and detectors (MS, TOFMS, FID, ECD, NPD, AED, O or EPD). Additionally, brief characteristics of internationally popular spirit-based beverages and application of gas chromatography to the analysis of selected alcoholic drinks are presented.

Estimating an Effect Size in One-Way Multivariate Analysis of Variance (MANOVA)

ERIC Educational Resources Information Center

Steyn, H. S., Jr.; Ellis, S. M.

2009-01-01

When two or more univariate population means are compared, the proportion of variation in the dependent variable accounted for by population group membership is eta-squared. This effect size can be generalized by using multivariate measures of association, based on the multivariate analysis of variance (MANOVA) statistics, to establish whether…

77 FR 38509 - Approval and Promulgation of Implementation Plans; South Carolina; Regional Haze State...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-28

... Carolina's 2018 projections are based on the State's technical analysis of the anticipated emissions rates... haze technical analyses was developed by the Visibility Improvement State and Tribal Association of the... appropriate documentation in its SIP of the technical analysis it used to assess the need for and...

Teaching ABC & Cost Behaviors to Non-Numbers People

ERIC Educational Resources Information Center

Taylor, Virginia Anne; Rudnick, Martin

2007-01-01

Simply put, a cost analysis studies how you spend your money. Activity based costing models associate costs with services and cost benefit analysis weighs whether or not the costs expended were worth the money given the efforts involved and the results achieved. This study seeks to understand the financial choices and information seeking behaviors…

Acknowledging Different Needs: Developing a Taxonomy of Welfare Leavers.

ERIC Educational Resources Information Center

Julnes, George; Hayashi, Kentaro; Anderson, Steven

2001-01-01

Used cluster analysis of survey data for 506 respondents to create a taxonomy of welfare leavers in Illinois based on their self-reported well-being after leaving welfare. Used classification tree analysis to identify factors associated with different types of leavers. Findings highlight the existence of many marginally successful leavers who…

Relationship between School Suspension and Student Outcomes: A Meta-Analysis

ERIC Educational Resources Information Center

Noltemeyer, Amity L.; Ward, Rose Marie; Mcloughlin, Caven

2015-01-01

Although the association between school suspension and deleterious outcomes is widely acknowledged, policy and practice need to be informed by an evidence base derived from multiple studies revealing consistent trends. This meta-analysis aims to address this void by examining the degree to which different types of school suspensions (in-school…

Views on the Efficacy and Ethics of Punishment: Results from a National Survey

ERIC Educational Resources Information Center

DiGennaro Reed, Florence D.; Lovett, Benjamin J.

2008-01-01

Punishment-based interventions are among the most controversial treatments in the applied behavior analysis literature. The controversy concerns both the efficacy and the ethics of punishment. Five hundred randomly selected members of the Association for Behavior Analysis were sent a survey concerning their views on the efficacy and ethics of…

Centre of pressure patterns in the golf swing: individual-based analysis.

PubMed

Ball, Kevin; Best, Russell

2012-06-01

Weight transfer has been identified as important in group-based analyses. The aim of this study was to extend this work by examining the importance of weight transfer in the golf swing on an individual basis. Five professional and amateur golfers performed 50 swings with the driver, hitting a ball into a net. The golfer's centre of pressure position and velocity, parallel with the line of shot, were measured by two force plates at eight swing events that were identified from high-speed video. The relationships between these parameters and club head velocity at ball contact were examined using regression statistics. The results did support the use of group-based analysis, with all golfers returning significant relationships. However, results were also individual-specific, with golfers returning different combinations of significant factors. Furthermore, factors not identified in group-based analysis were significant on an individual basis. The most consistent relationship was a larger weight transfer range associated with a larger club head velocity (p < 0.05). All golfers also returned at least one significant relationship with rate of weight transfer at swing events (p < 0.01). Individual-based analysis should form part of performance-based biomechanical analysis of sporting skills.

Intratumor partitioning and texture analysis of dynamic contrast-enhanced (DCE)-MRI identifies relevant tumor subregions to predict pathological response of breast cancer to neoadjuvant chemotherapy.

PubMed

Wu, Jia; Gong, Guanghua; Cui, Yi; Li, Ruijiang

2016-11-01

To predict pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multiregion analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). In this Institutional Review Board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using 3T DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with high temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast washout were statistically significant (P < 0.05) after correcting for multiple testing, with area under the receiver operating characteristic (ROC) curve (AUC) or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (P = 0.002) in leave-one-out cross-validation. This improved upon conventional imaging predictors such as tumor volume (AUC = 0.53) and texture features based on whole-tumor analysis (AUC = 0.65). The heterogeneity of the tumor subregion associated with fast washout on DCE-MRI predicted pathological response to NAC in breast cancer. J. Magn. Reson. Imaging 2016;44:1107-1115. © 2016 International Society for Magnetic Resonance in Medicine.

MetaSeq: privacy preserving meta-analysis of sequencing-based association studies.

PubMed

Singh, Angad Pal; Zafer, Samreen; Pe'er, Itsik

2013-01-01

Human genetics recently transitioned from GWAS to studies based on NGS data. For GWAS, small effects dictated large sample sizes, typically made possible through meta-analysis by exchanging summary statistics across consortia. NGS studies groupwise-test for association of multiple potentially-causal alleles along each gene. They are subject to similar power constraints and therefore likely to resort to meta-analysis as well. The problem arises when considering privacy of the genetic information during the data-exchange process. Many scoring schemes for NGS association rely on the frequency of each variant thus requiring the exchange of identity of the sequenced variant. As such variants are often rare, potentially revealing the identity of their carriers and jeopardizing privacy. We have thus developed MetaSeq, a protocol for meta-analysis of genome-wide sequencing data by multiple collaborating parties, scoring association for rare variants pooled per gene across all parties. We tackle the challenge of tallying frequency counts of rare, sequenced alleles, for metaanalysis of sequencing data without disclosing the allele identity and counts, thereby protecting sample identity. This apparent paradoxical exchange of information is achieved through cryptographic means. The key idea is that parties encrypt identity of genes and variants. When they transfer information about frequency counts in cases and controls, the exchanged data does not convey the identity of a mutation and therefore does not expose carrier identity. The exchange relies on a 3rd party, trusted to follow the protocol although not trusted to learn about the raw data. We show applicability of this method to publicly available exome-sequencing data from multiple studies, simulating phenotypic information for powerful meta-analysis. The MetaSeq software is publicly available as open source.

A comparative analysis of moral principles and behavioral norms in eight ethical codes relevant to health sciences librarianship, medical informatics, and the health professions.

PubMed

Byrd, Gary D; Winkelstein, Peter

2014-10-01

Based on the authors' shared interest in the interprofessional challenges surrounding health information management, this study explores the degree to which librarians, informatics professionals, and core health professionals in medicine, nursing, and public health share common ethical behavior norms grounded in moral principles. Using the "Principlism" framework from a widely cited textbook of biomedical ethics, the authors analyze the statements in the ethical codes for associations of librarians (Medical Library Association [MLA], American Library Association, and Special Libraries Association), informatics professionals (American Medical Informatics Association [AMIA] and American Health Information Management Association), and core health professionals (American Medical Association, American Nurses Association, and American Public Health Association). This analysis focuses on whether and how the statements in these eight codes specify core moral norms (Autonomy, Beneficence, Non-Maleficence, and Justice), core behavioral norms (Veracity, Privacy, Confidentiality, and Fidelity), and other norms that are empirically derived from the code statements. These eight ethical codes share a large number of common behavioral norms based most frequently on the principle of Beneficence, then on Autonomy and Justice, but rarely on Non-Maleficence. The MLA and AMIA codes share the largest number of common behavioral norms, and these two associations also share many norms with the other six associations. The shared core of behavioral norms among these professions, all grounded in core moral principles, point to many opportunities for building effective interprofessional communication and collaboration regarding the development, management, and use of health information resources and technologies.

A comparative analysis of moral principles and behavioral norms in eight ethical codes relevant to health sciences librarianship, medical informatics, and the health professions

PubMed Central

Byrd, Gary D.; Winkelstein, Peter

2014-01-01

Objective: Based on the authors' shared interest in the interprofessional challenges surrounding health information management, this study explores the degree to which librarians, informatics professionals, and core health professionals in medicine, nursing, and public health share common ethical behavior norms grounded in moral principles. Methods: Using the “Principlism” framework from a widely cited textbook of biomedical ethics, the authors analyze the statements in the ethical codes for associations of librarians (Medical Library Association [MLA], American Library Association, and Special Libraries Association), informatics professionals (American Medical Informatics Association [AMIA] and American Health Information Management Association), and core health professionals (American Medical Association, American Nurses Association, and American Public Health Association). This analysis focuses on whether and how the statements in these eight codes specify core moral norms (Autonomy, Beneficence, Non-Maleficence, and Justice), core behavioral norms (Veracity, Privacy, Confidentiality, and Fidelity), and other norms that are empirically derived from the code statements. Results: These eight ethical codes share a large number of common behavioral norms based most frequently on the principle of Beneficence, then on Autonomy and Justice, but rarely on Non-Maleficence. The MLA and AMIA codes share the largest number of common behavioral norms, and these two associations also share many norms with the other six associations. Implications: The shared core of behavioral norms among these professions, all grounded in core moral principles, point to many opportunities for building effective interprofessional communication and collaboration regarding the development, management, and use of health information resources and technologies. PMID:25349543

Functional relevance for type 1 diabetes mellitus-associated genetic variants by using integrative analyses.

PubMed

Qiu, Ying-Hua; Deng, Fei-Yan; Tang, Zai-Xiang; Jiang, Zhen-Huan; Lei, Shu-Feng

2015-10-01

Type 1 diabetes mellitus (type 1 DM) is an autoimmune disease. Although genome-wide association studies (GWAS) and meta-analyses have successfully identified numerous type 1 DM-associated susceptibility loci, the underlying mechanisms for these susceptibility loci are currently largely unclear. Based on publicly available datasets, we performed integrative analyses (i.e., integrated gene relationships among implicated loci, differential gene expression analysis, functional prediction and functional annotation clustering analysis) and combined with expression quantitative trait loci (eQTL) results to further explore function mechanisms underlying the associations between genetic variants and type 1 DM. Among a total of 183 type 1 DM-associated SNPs, eQTL analysis showed that 17 SNPs with cis-regulated eQTL effects on 9 genes. All the 9 eQTL genes enrich in immune-related pathways or Gene Ontology (GO) terms. Functional prediction analysis identified 5 SNPs located in transcription factor (TF) binding sites. Of the 9 eQTL genes, 6 (TAP2, HLA-DOB, HLA-DQB1, HLA-DQA1, HLA-DRB5 and CTSH) were differentially expressed in type 1 DM-associated related cells. Especially, rs3825932 in CTSH has integrative functional evidence supporting the association with type 1 DM. These findings indicated that integrative analyses can yield important functional information to link genetic variants and type 1 DM. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Variants of the MTHFR gene and susceptibility to acute lymphoblastic leukemia in children: a synthesis of genetic association studies.

PubMed

Zintzaras, Elias; Doxani, Chrysoula; Rodopoulou, Paraskevi; Bakalos, Georgios; Ziogas, Dimitris C; Ziakas, Panayiotis; Voulgarelis, Michael

2012-04-01

Acute lymphoblastic leukemia (ALL) is a complex disease with genetic background. The genetic association studies (GAS) that investigated the association between ALL and the MTHFR C677T and A1298C gene variants have produced contradictory or inconclusive results. In order to decrease the uncertainty of estimated genetic risk effects, a meticulous meta-analysis of published GAS related the variants in the MTFHR gene with susceptibility to ALL was conducted. The risk effects were estimated based on the odds ratio (OR) of the allele contrast and the generalized odds ratio (OR(G)). Cumulative and recursive cumulative meta-analyses were also performed. The analysis showed marginal significant association for the C677T variant, overall [OR=0.91 (0.82-1.00) and OR(G)=0.89 (0.79-1.01)], and in Whites [OR=0.88 (0.77-0.99) and OR(G)=0.85 (0.73-0.99)]. The A1298C variant produced non-significant results. For both variants, the cumulative meta-analysis did not show a trend of association as evidence accumulates and the recursive cumulative meta-analysis indicated lack of sufficient evidence for denying or claiming an association. The current evidence is not sufficient to draw definite conclusions regarding the association of MTHFR variants and development of ALL. Copyright © 2011 Elsevier Ltd. All rights reserved.

Apolipoprotein C3 Gene Polymorphisms Are Not a Risk Factor for Developing Non-Alcoholic Fatty Liver Disease: A Meta-Analysis

PubMed Central

Zhang, Haiying; Chen, Lizhen; Xin, Yongning; Lou, Yuangui; Liu, Yang; Xuan, Shiying

2014-01-01

Context: Our objective was to evaluate the effect of gene polymorphisms of apolipoprotein C3 (APOC3) on the development of non-alcoholic fatty liver disease (NAFLD) in different populations. Evidence Acquisition: We performed a meta-analysis of all relevant studies published in the literature. A total of 115 clinical trials or reports were identified, but only seven trials met our inclusion criteria. A meta-analysis was performed according to the Cochrane Reviewers’ Handbook recommendations. Results: Five hospital-based and two population-based case-control studies were included in the final analysis. The overall frequency of APOC3 gene polymorphisms was 67.5% (1177/1745) in NAFLD and 68.8% (988/1437) in controls. The summary odds ratio for the association of gene polymorphisms of APOC3 and the risk of NAFLD was 1.03 (95% CI: 0.89-1.22),which was not statistically significant (P > 0.05). Conclusions: Our meta-analysis, while not ruling out possible publication bias, showed no association between gene polymorphisms of APOC3 and the risk of NAFLD development in different populations in the world. PMID:25477977

Network structure of multivariate time series.

PubMed

Lacasa, Lucas; Nicosia, Vincenzo; Latora, Vito

2015-10-21

Our understanding of a variety of phenomena in physics, biology and economics crucially depends on the analysis of multivariate time series. While a wide range tools and techniques for time series analysis already exist, the increasing availability of massive data structures calls for new approaches for multidimensional signal processing. We present here a non-parametric method to analyse multivariate time series, based on the mapping of a multidimensional time series into a multilayer network, which allows to extract information on a high dimensional dynamical system through the analysis of the structure of the associated multiplex network. The method is simple to implement, general, scalable, does not require ad hoc phase space partitioning, and is thus suitable for the analysis of large, heterogeneous and non-stationary time series. We show that simple structural descriptors of the associated multiplex networks allow to extract and quantify nontrivial properties of coupled chaotic maps, including the transition between different dynamical phases and the onset of various types of synchronization. As a concrete example we then study financial time series, showing that a multiplex network analysis can efficiently discriminate crises from periods of financial stability, where standard methods based on time-series symbolization often fail.

[Fine mapping of complex disease susceptibility loci].

PubMed

Song, Qingfeng; Zhang, Hongxing; Ma, Yilong; Zhou, Gangqiao

2014-01-01

Genome-wide association studies (GWAS) using single nucleotide polymorphism (SNP) markers have identified more than 3800 susceptibility loci for more than 660 diseases or traits. However, the most significantly associated variants or causative variants in these loci and their biological functions have remained to be clarified. These causative variants can help to elucidate the pathogenesis and discover new biomarkers of complex diseases. One of the main goals in the post-GWAS era is to identify the causative variants and susceptibility genes, and clarify their functional aspects by fine mapping. For common variants, imputation or re-sequencing based strategies were implemented to increase the number of analyzed variants and help to identify the most significantly associated variants. In addition, functional element, expression quantitative trait locus (eQTL) and haplotype analyses were performed to identify functional common variants and susceptibility genes. For rare variants, fine mapping was carried out by re-sequencing, rare haplotype analysis, family-based analysis, burden test, etc.This review summarizes the strategies and problems for fine mapping.

Gender roles, eating pathology, and body dissatisfaction in men: a meta-analysis.

PubMed

Blashill, Aaron J

2011-01-01

The current study reviewed relationships between gender roles and (a) eating pathology, (b) body dissatisfaction, and (c) muscle dissatisfaction among men via meta-analysis. Moderators of sexual orientation and type of gender role measure were also investigated. Results revealed the relationship between femininity and eating and body-related variables did not significantly differ from zero. Sexual orientation moderated the relationship between femininity and muscle dissatisfaction (i.e., femininity was negatively related to muscle dissatisfaction for heterosexual but not gay men). Masculinity was negatively associated with eating pathology and body dissatisfaction. Type of masculinity measure moderated the relationship between masculinity and body dissatisfaction (i.e., trait-based measures produced a negative association, multidimensional measures yielded nonsignificant relationships). Type of masculinity measure produced a cross-over interaction when examining muscle dissatisfaction (i.e., trait-based instruments yielded a negative association and multidimensional instruments revealed a positive relationship). Findings highlight the salience of masculinity in men's eating and body concerns. Copyright © 2010 Elsevier Ltd. All rights reserved.

Disclosure appraisal mediating the association between perceived stigma and HIV disclosure to casual sex partners among HIV+ MSM: a path model analysis.

PubMed

Li, Haochu; Chen, Xinguang; Yu, Bin

2016-01-01

HIV stigma is widely believed to be related to HIV disclosure. However, there is a dearth of studies examining the mechanisms that link stigma to disclosure. This is a specific study to assess the relationship between perceived stigma and HIV disclosure to casual sex partners based on a social cognitive theory. HIV+ men who have sex with men (MSM) from two US cities (N = 297) completed questionnaires administered using audio computer-assisted self-interviewing. Path modeling analysis was used to assess the theory-based structural relationships. Perceived stigma was negatively associated with attitudes, intention and behavior of HIV disclosure to casual sex partners. The association was fully mediated by disclosure appraisal, including disclosure outcome expectations, costs and self-efficacy. Findings of this study add new knowledge regarding HIV stigma and disclosure, and provide timely data supporting more effective behavioral interventions to encourage HIV disclosure among MSM.

A New Search Paradigm for Correlated Neutrino Emission from Discrete GRBs using Antarctic Cherenkov Telescopes in the Swift Era

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stamatikos, Michael; Band, David L.; JCA/UMBC, Baltimore, MD 21250

2006-05-19

We describe the theoretical modeling and analysis techniques associated with a preliminary search for correlated neutrino emission from GRB980703a, which triggered the Burst and Transient Source Experiment (BATSE GRB trigger 6891), using archived data from the Antarctic Muon and Neutrino Detector Array (AMANDA-B10). Under the assumption of associated hadronic acceleration, the expected observed neutrino energy flux is directly derived, based upon confronting the fireball phenomenology with the discrete set of observed electromagnetic parameters of GRB980703a, gleaned from ground-based and satellite observations, for four models, corrected for oscillations. Models 1 and 2, based upon spectral analysis featuring a prompt photon energymore » fit to the Band function, utilize an observed spectroscopic redshift, for isotropic and anisotropic emission geometry, respectively. Model 3 is based upon averaged burst parameters, assuming isotropic emission. Model 4 based upon a Band fit, features an estimated redshift from the lag-luminosity relation, with isotropic emission. Consistent with our AMANDA-II analysis of GRB030329, which resulted in a flux upper limit of {approx} 0.150GeV /cm2/s for model 1, we find differences in excess of an order of magnitude in the response of AMANDA-B10, among the various models for GRB980703a. Implications for future searches in the era of Swift and IceCube are discussed.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, J; Gong, G; Cui, Y

Purpose: To predict early pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multi-region analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: In this institution review board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with a high-temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitativemore » Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Results: Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast wash-out were statistically significant (p< 0.05) after correcting for multiple testing, with area under the ROC curve or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (p = 0.002) in leave-one-out cross validation. This improved upon conventional imaging predictors such as tumor volume (AUC=0.53) and texture features based on whole-tumor analysis (AUC=0.65). Conclusion: The heterogeneity of the tumor subregion associated with fast wash-out on DCE-MRI predicted early pathological response to neoadjuvant chemotherapy in breast cancer.« less

The Association of GSDMB and ORMDL3 Gene Polymorphisms With Asthma: A Meta-Analysis.

PubMed

Zhao, Chun-Ni; Fan, Ye; Huang, Jian-Jun; Zhang, Hai-Xia; Gao, Tao; Wang, Cong; Wang, Tong; Hou, Li-Fang

2015-03-01

ORM1-like 3 (ORMDL3) belongs to a highly conserved protein family which is anchored as transmembrane protein in the endoplasmic reticulum. Gasdermin B (GSDMB) is adjacent to ORMDL3 on chromosome 17q21.2 and belongs to the gasdermin-domain containing the protein family (GSDM family). Recent reports suggest that GSDMB and ORMDL3 are associated with asthma in several populations. However, genetic association studies that examined the association of GSDMB and ORMDL3 gene variants with asthma showed conflicting results. To assess whether combined evidence shows the association between GSDMB/ORMDL3 polymorphism and asthma. A bibliographic search from MEDLINE identified 13 original articles using the search keywords 'GSDMB', 'ORMDL3', and 'asthma'. An updated literature-based meta-analysis involving 6,691 subjects with asthma, 9,281 control individuals, and 1,360 families were conducted. Meta-odds ratios (ORs) and 95% confidence intervals (CIs) based on the fixed effects model or the random effects model depended on Cochran's Q-statistic and I(2) values. Data from case-control and TDT studies were analyzed in an allelic model using the Catmap software. We selected and identified 3 SNPs of ORMDL3 associated with asthma (rs8076131: OR=1.10; 95% CI, 1.02-1.20; P=0.012. rs12603332: OR=1.15; 95% CI, 1.05-1.25; P=0.002. rs3744246: OR=1.10; 95% CI, 1.02-1.17; P=0.008) and 1 SNP of GSDMB associated with asthma (rs7216389: OR=1.37; 95% CI, 1.27-1.47; P<0.01). Publication bias was estimated using modified Egger's linear regression test proposed by Harbordetal and revealed no evidence of biases. Furthermore, cumulative meta-analysis in chronological order showed the inclination toward significant association for rs7216389 and rs12603332 with continually adding studies, and the inclination toward null-significant association for rs3744246 and rs8076131. Moderate evidence exists for associations of the ORMDL3 rs8076131, rs12603332, and rs3744246 and GSDMB rs7216389 variants with asthma. Large sample size and representative population-based studies and TDT studies with homogeneous asthmatic patients and well-matched controls are warranted to confirm this finding.

The Association of GSDMB and ORMDL3 Gene Polymorphisms With Asthma: A Meta-Analysis

PubMed Central

Zhao, Chun-Ni; Fan, Ye; Huang, Jian-Jun; Zhang, Hai-Xia; Gao, Tao; Wang, Cong; Hou, Li-Fang

2015-01-01

Purpose ORM1-like 3 (ORMDL3) belongs to a highly conserved protein family which is anchored as transmembrane protein in the endoplasmic reticulum. Gasdermin B (GSDMB) is adjacent to ORMDL3 on chromosome 17q21.2 and belongs to the gasdermin-domain containing the protein family (GSDM family). Recent reports suggest that GSDMB and ORMDL3 are associated with asthma in several populations. However, genetic association studies that examined the association of GSDMB and ORMDL3 gene variants with asthma showed conflicting results. To assess whether combined evidence shows the association between GSDMB/ORMDL3 polymorphism and asthma. Methods A bibliographic search from MEDLINE identified 13 original articles using the search keywords 'GSDMB', 'ORMDL3', and 'asthma'. An updated literature-based meta-analysis involving 6,691 subjects with asthma, 9,281 control individuals, and 1,360 families were conducted. Meta-odds ratios (ORs) and 95% confidence intervals (CIs) based on the fixed effects model or the random effects model depended on Cochran's Q-statistic and I2 values. Data from case-control and TDT studies were analyzed in an allelic model using the Catmap software. Results We selected and identified 3 SNPs of ORMDL3 associated with asthma (rs8076131: OR=1.10; 95% CI, 1.02-1.20; P=0.012. rs12603332: OR=1.15; 95% CI, 1.05-1.25; P=0.002. rs3744246: OR=1.10; 95% CI, 1.02-1.17; P=0.008) and 1 SNP of GSDMB associated with asthma (rs7216389: OR=1.37; 95% CI, 1.27-1.47; P<0.01). Publication bias was estimated using modified Egger's linear regression test proposed by Harbordetal and revealed no evidence of biases. Furthermore, cumulative meta-analysis in chronological order showed the inclination toward significant association for rs7216389 and rs12603332 with continually adding studies, and the inclination toward null-significant association for rs3744246 and rs8076131. Conclusions Moderate evidence exists for associations of the ORMDL3 rs8076131, rs12603332, and rs3744246 and GSDMB rs7216389 variants with asthma. Large sample size and representative population-based studies and TDT studies with homogeneous asthmatic patients and well-matched controls are warranted to confirm this finding. PMID:25729625

Association Rule Analysis for Tour Route Recommendation and Application to Wctsnop

NASA Astrophysics Data System (ADS)

Fang, H.; Chen, C.; Lin, J.; Liu, X.; Fang, D.

2017-09-01

The increasing E-tourism systems provide intelligent tour recommendation for tourists. In this sense, recommender system can make personalized suggestions and provide satisfied information associated with their tour cycle. Data mining is a proper tool that extracting potential information from large database for making strategic decisions. In the study, association rule analysis based on FP-growth algorithm is applied to find the association relationship among scenic spots in different cities as tour route recommendation. In order to figure out valuable rules, Kulczynski interestingness measure is adopted and imbalance ratio is computed. The proposed scheme was evaluated on Wangluzhe cultural tourism service network operation platform (WCTSNOP), where it could verify that it is able to quick recommend tour route and to rapidly enhance the recommendation quality.

Stability analysis for stochastic BAM nonlinear neural network with delays

NASA Astrophysics Data System (ADS)

Lv, Z. W.; Shu, H. S.; Wei, G. L.

2008-02-01

In this paper, stochastic bidirectional associative memory neural networks with constant or time-varying delays is considered. Based on a Lyapunov-Krasovskii functional and the stochastic stability analysis theory, we derive several sufficient conditions in order to guarantee the global asymptotically stable in the mean square. Our investigation shows that the stochastic bidirectional associative memory neural networks are globally asymptotically stable in the mean square if there are solutions to some linear matrix inequalities(LMIs). Hence, the global asymptotic stability of the stochastic bidirectional associative memory neural networks can be easily checked by the Matlab LMI toolbox. A numerical example is given to demonstrate the usefulness of the proposed global asymptotic stability criteria.

The impact of extracurricular activities participation on youth delinquent behaviors: An instrumental variables approach.

PubMed

Han, Sehee; Lee, Jonathan; Park, Kyung-Gook

2017-07-01

The purpose of this study was to examine the association between extracurricular activities (EA) participation and youth delinquency while tackling an endogeneity problem of EA participation. Using survey data of 12th graders in South Korea (n = 1943), this study employed an instrumental variables approach to address the self-selection problem of EA participation as the data for this study was based on an observational study design. We found a positive association between EA participation and youth delinquency based on conventional regression analysis. By contrast, we found a negative association between EA participation and youth delinquency based on an instrumental variables approach. These results indicate that caution should be exercised when we interpret the effect of EA participation on youth delinquency based on observational study designs. Copyright © 2017 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies

PubMed Central

Antoniou, A; Pharoah, P; Narod, S; Risch, H; Eyfjord, J; Hopper, J; Olsson, H; Johannsson, O; Borg, A; Pasini, B; Radice, P; Manoukian, S; Eccles, D; Tang, N; Olah, E; Anton-Culver, H; Warner, E; Lubinski, J; Gronwald, J; Gorski, B; Tulinius, H; Thorlacius, S; Eerola, H; Nevanlinna, H; Syrjakoski, K; Kallioniemi, O; Thompson, D; Evans, C; Peto, J; Lalloo, F; Evans, D; Easton, D

2005-01-01

A recent report estimated the breast cancer risks in carriers of the three Ashkenazi founder mutations to be higher than previously published estimates derived from population based studies. In an attempt to confirm this, the breast and ovarian cancer risks associated with the three Ashkenazi founder mutations were estimated using families included in a previous meta-analysis of populatrion based studies. The estimated breast cancer risks for each of the founder BRCA1 and BRCA2 mutations were similar to the corresponding estimates based on all BRCA1 or BRCA2 mutations in the meta-analysis. These estimates appear to be consistent with the observed prevalence of the mutations in the Ashkenazi Jewish population. PMID:15994883

Hearing impairment associated with oral terbinafine use: a case series and case/non-case analysis in the Netherlands Pharmacovigilance Centre Lareb database and VigiBase™.

PubMed

Scholl, Joep H G; van Puijenbroek, Eugene P

2012-08-01

The Netherlands Pharmacovigilance Centre Lareb received reports of six cases of hearing impairment in association with oral terbinafine use. This study describes these cases and provides support for this association from the Lareb database for spontaneous adverse drug reaction (ADR) reporting and from Vigibase™, the ADR database of the WHO Collaborating Centre for International Drug Monitoring, the Uppsala Monitoring Centre. The objective of the current study was to identify whether the observed association between oral terbinafine use and hearing impairment, based on cases received by Lareb, constitutes a safety signal. Cases of hearing impairment in oral terbinafine users are described. In a case/non-case analysis, the strength of the association in Vigibase™ and the Lareb database was determined (date of analysis August 2011) by calculating the reporting odds ratios (RORs), adjusted for possible confounding by age, sex and ototoxic concomitant medication. For the purpose of this study, RORs were calculated for deafness, hypoacusis and the combination of both, defined as hearing impairment. In the Lareb database, six reports concerning individuals aged 31-82 years, who developed hearing impairment after starting oral terbinafine, were present. The use of oral terbinafine was disproportionally associated with hypoacusis in both the Lareb database (adjusted ROR 3.9; 95% CI 1.7, 9.0) and in Vigibase™ (adjusted ROR 1.7; 95% CI 1.0, 2.8). Deafness was not disproportionally present in either of the databases. Based on the described cases and the statistical analyses from both databases, a causal relationship between the use of oral terbinafine and hearing impairment is possible. The mechanism by which terbinafine could cause hearing impairment has not been elucidated yet. The pharmacological action of terbinafine is based on the inhibition of squalene epoxidase, an enzyme present in both fungal and human cells. This inhibition might result in a decrease in cholesterol levels in human cells, among which are the outer hair cells of the cochlea. It may be possible that the reduction in cochlear cholesterol levels leads to impaired cochlear function and possibly hearing impairment. In this study we describe hearing impairment as a possible ADR of oral terbinafine, based on six case reports and statistical support from Vigibase™ and the Lareb database. To our knowledge this association has not been described before.

Association Between US State Medical Cannabis Laws and Opioid Prescribing in the Medicare Part D Population.

PubMed

Bradford, Ashley C; Bradford, W David; Abraham, Amanda; Bagwell Adams, Grace

2018-05-01

Opioid-related mortality increased by 15.6% from 2014 to 2015 and increased almost 320% between 2000 and 2015. Recent research finds that the use of all pain medications (opioid and nonopioid collectively) decreases in Medicare Part D and Medicaid populations when states approve medical cannabis laws (MCLs). The association between MCLs and opioid prescriptions is not well understood. To examine the association between prescribing patterns for opioids in Medicare Part D and the implementation of state MCLs. Longitudinal analysis of the daily doses of opioids filled in Medicare Part D for all opioids as a group and for categories of opioids by state and state-level MCLs from 2010 through 2015. Separate models were estimated first for whether the state had implemented any MCL and second for whether a state had implemented either a dispensary-based or a home cultivation only-based MCL. The primary outcome measure was the total number of daily opioid doses prescribed (in millions) in each US state for all opioids. The secondary analysis examined the association between MCLs separately by opioid class. From 2010 to 2015 there were 23.08 million daily doses of any opioid dispensed per year in the average state under Medicare Part D. Multiple regression analysis results found that patients filled fewer daily doses of any opioid in states with an MCL. The associations between MCLs and any opioid prescribing were statistically significant when we took the type of MCL into account: states with active dispensaries saw 3.742 million fewer daily doses filled (95% CI, -6.289 to -1.194); states with home cultivation only MCLs saw 1.792 million fewer filled daily doses (95% CI, -3.532 to -0.052). Results varied by type of opioid, with statistically significant estimated negative associations observed for hydrocodone and morphine. Hydrocodone use decreased by 2.320 million daily doses (or 17.4%) filled with dispensary-based MCLs (95% CI, -3.782 to -0.859; P = .002) and decreased by 1.256 million daily doses (or 9.4%) filled with home-cultivation-only-based MCLs (95% CI, -2.319 to -0.193; P = .02). Morphine use decreased by 0.361 million daily doses (or 20.7%) filled with dispensary-based MCLs (95% CI, -0.718 to -0.005; P = .047). Medical cannabis laws are associated with significant reductions in opioid prescribing in the Medicare Part D population. This finding was particularly strong in states that permit dispensaries, and for reductions in hydrocodone and morphine prescriptions.

Association between polymorphisms in the β2-adrenergic receptor gene with myocardial infarction and ischemic stroke in women

PubMed Central

Schürks, Markus; Kurth, Tobias; Ridker, Paul M; Buring, Julie E.; Zee, Robert Y. L.

2008-01-01

Summary Results from studies investigating the association between polymorphisms in the β2-adrenergic receptor gene (ADRB2) and cardiovascular disease (CVD) are controversial. Using haplotype-based analysis, we have previously shown a protective effect of the Gly16-Gln27-Ile164 haplotype on myocardial infarction in men. We sought to replicate these findings in women and further investigated, whether the gene variants exert differential effects on myocardial infarction and ischemic stroke. We performed a prospective study among 25,224 women, participating in the Women's Health Study and free of CVD at study entry. We had information on polymorphisms Gly16Arg, Gln27Glu, and Thr164Ile in the ADRB2. Incident CVD was self-reported and confirmed after medical record review. We used proportional hazards models to investigate the association between genotypes and haplotypes with any myocardial infarction, any ischemic stroke, and CVD death. During a mean of 11.8 years of follow-up, 274 myocardial infarctions, 299 ischemic strokes, and 159 CVD deaths occurred. Among the whole cohort genotype- and haplotype-based analyses did not show an association for any of the gene variants with any of the CVD outcomes. When we focused on Caucasian women, the haplotype-based analysis, however, suggested an inverse association of the haplotype Gly16-Gln27-Thr164 with incident myocardial infarction (multivariable-adjusted hazard ratio 0.75; 95%CI 0.58−0.97; p=0.03). We did not find associations in the haplotype-based analyses with incident ischemic stroke or CVD death. Our results suggest that the haplotype Gly16-Gln27-Thr164 is associated with reduced risk of incident myocardial infarction but not ischemic stroke in Caucasian women and suggests differential pathophysiologies for myocardial infarction and stroke. PMID:19190821

Case study approach to modeling historical disinfection by-product exposure in Iowa drinking waters.

PubMed

Krasner, Stuart W; Cantor, Kenneth P; Weyer, Peter J; Hildesheim, Mariana; Amy, Gary

2017-08-01

In the 1980s, a case-control epidemiologic study was conducted in Iowa (USA) to analyze the association between exposure to disinfection by-products (DBPs) and bladder cancer risk. Trihalomethanes (THMs), the most commonly measured and dominant class of DBPs in drinking water, served as a primary metric and surrogate for the full DBP mixture. Average THM exposure was calculated, based on rough estimates of past levels in Iowa. To reduce misclassification, a follow-up study was undertaken to improve estimates of past THM levels and to re-evaluate their association with cancer risk. In addition, the risk associated with haloacetic acids, another class of DBPs, was examined. In the original analysis, surface water treatment plants were assigned one of two possible THM levels depending on the point of chlorination. The re-assessment considered each utility treating surface or groundwater on a case-by-case basis. Multiple treatment/disinfection scenarios and water quality parameters were considered with actual DBP measurements to develop estimates of past levels. The highest annual average THM level in the re-analysis was 156μg/L compared to 74μg/L for the original analysis. This allowed the analysis of subjects exposed at higher levels (>96μg/L). The re-analysis established a new approach, based on case studies and an understanding of the water quality and operational parameters that impact DBP formation, for determining historical exposure. Copyright © 2017. Published by Elsevier B.V.

Analysis of Parametric Adaptive Signal Detection with Applications to Radars and Hyperspectral Imaging

DTIC Science & Technology

2010-02-01

98 8.4.5 Training Screening ............................. .................................................................99 8.5 Experimental...associated with the proposed parametric model. Several im- portant issues are discussed, including model order selection, training screening , and time...parameters associated with the NS-AR model. In addition, we develop model order selection, training screening , and time-series based whitening and

Analysis of Influential Factors Associated with the Smoking Behavior of Aboriginal Schoolchildren in Remote Taiwanese Mountainous Areas

ERIC Educational Resources Information Center

Huang, Hsiao-Ling; Hsu, Chih-Cheng; Peng, Wu-Der; Yen, Yea-Yin; Chen, Ted; Hu, Chih-Yang; Shi, Hon-Yi; Lee, Chien-Hung; Chen, Fu-Li; Lin, Pi-Li

2012-01-01

Background: A disparity in smoking behavior exists between the general and minority populations residing in Taiwan's mountainous areas. This study analyzed individual and environmental factors associated with children's smoking behavior in these areas of Taiwan. Methods: In this school-based study, data on smoking behavior and related factors for…

Which Variables Associated with Data-Driven Instruction Are Believed to Best Predict Urban Student Achievement?

ERIC Educational Resources Information Center

Greer, Wil

2013-01-01

This study identified the variables associated with data-driven instruction (DDI) that are perceived to best predict student achievement. Of the DDI variables discussed in the literature, 51 of them had a sufficient enough research base to warrant statistical analysis. Of them, 26 were statistically significant. Multiple regression and an…

Shuttle program. STS-7 feasibility assessment: IUS/TDRS-A

NASA Technical Reports Server (NTRS)

1979-01-01

This Space Transportation System 7 (STS-7) Flight Feasibility Assessment (FFA) provides a base from which the various design, operation, and integration elements associated with Tracking and Data Relay Satellite-A can perform mission planning and analysis. The STS-7 FFA identifies conflicts, issues, and concerns associated with the integrated flight design requirements and constraints.

IMS - MS Data Extractor

DOE Office of Scientific and Technical Information (OSTI.GOV)

2015-10-20

An automated drift time extraction and computed associated collision cross section software tool for small molecule analysis with ion mobility spectrometry-mass spectrometry (IMS-MS). The software automatically extracts drift times and computes associated collision cross sections for small molecules analyzed using ion mobility spectrometry-mass spectrometry (IMS-MS) based on a target list of expected ions provided by the user.