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Sample records for population association analysis

  1. Accounting for linkage disequilibrium in association analysis of diverse populations.

    PubMed

    Charles, Bashira A; Shriner, Daniel; Rotimi, Charles N

    2014-04-01

    The National Human Genome Research Institute's catalog of published genome-wide association studies (GWAS) lists over 10,000 genetic variants collectively associated with over 800 human diseases or traits. Most of these GWAS have been conducted in European-ancestry populations. Findings gleaned from these studies have led to identification of disease-associated loci and biologic pathways involved in disease etiology. In multiple instances, these genomic findings have led to the development of novel medical therapies or evidence for prescribing a given drug as the appropriate treatment for a given individual beyond phenotypic appearances or socially defined constructs of race or ethnicity. Such findings have implications for populations throughout the globe and GWAS are increasingly being conducted in more diverse populations. A major challenge for investigators seeking to follow up genomic findings between diverse populations is discordant patterns of linkage disequilibrium (LD). We provide an overview of common measures of LD and opportunities for their use in novel methods designed to address challenges associated with following up GWAS conducted in European-ancestry populations in African-ancestry populations or, more generally, between populations with discordant LD patterns. We detail the strengths and weaknesses associated with different approaches. We also describe application of these strategies in follow-up studies of populations with concordant LD patterns (replication) or discordant LD patterns (transferability) as well as fine-mapping studies. We review application of these methods to a variety of traits and diseases.

  2. Association between KIR polymorphisms and ankylosing spondylitis in populations: a meta-analysis.

    PubMed

    Fan, Dazhi; Liu, Si; Yang, Ting; Wu, Shanshan; Wang, Sheng; Li, Guixing; Zeng, Zhen; Duan, Zhenhua; Xia, Guo; Ye, Dongqing; Zou, Yanfeng; Xu, Shengqian; Xu, Jianhua; Zhang, Li; Shuai, Zongwen; Pan, Faming

    2014-11-01

    Published association studies of killer cell immunoglobulin-like receptors (KIRs) and ankylosing spondylitis (AS) in populations are inconsistent. The aim of this study is to determine whether the KIR polymorphisms confer susceptibility to AS in populations by conducting a meta-analysis. A computer search was carried out up to August 2013 for literature pertaining to AS and KIR polymorphisms. Publications addressing the association between the KIR polymorphisms and susceptibility to AS in populations were selected from the Pubmed, Elsevier Science Direct, China National Knowledge Infrastructure (CNKI) and Chinese Biomedical Literature Database (CBM) databases. The odds ratio (OR) with 95% confidence interval (95%CI) was calculated. A total of 13 case-control studies in 9 articles were included in this meta-analysis. Meta-analysis results identified two positive associations of 2DS4 and 3DS1 with susceptibility to AS in populations. In subgroup analysis, there was a positive association between 2DS4 and susceptibility to AS in Asians, but not in Caucasians. And there were associations between 3DL1, 3DS1 and susceptibility to AS in Caucasians, but not in Asians. Results of subgroup analysis also showed that there were associations between 2DL5, 2DS4, 2DS5, 3DL1, 3DS1 and susceptibility to AS in HLA-B*27-positive patients and HLA-B*27-positive healthy controls. This meta-analysis confirms that 2DS4 and 3DS1 might be potential risk factors for AS in populations.

  3. [Analysis of population stratification using random SNPs in genome-wide association studies].

    PubMed

    Cao, Zong-Fu; Ma, Chuan-Xiang; Wang, Lei; Cai, Bin

    2010-09-01

    Since population genetic STRUCTURE can increase false-positive rate in genome-wide association studies (GWAS) for complex diseases, the effect of population stratification should be taken into account in GWAS. However, the effect of randomly selected SNPs in population stratification analysis is underdetermined. In this study, based on the genotype data generated on Genome-Wide Human SNP Array 6.0 from unrelated individuals of HapMap Phase2, we randomly selected SNPs that were evenly distributed across the whole-genome, and acquired Ancestry Informative Markers (AIMs) by the method of f value and allelic Fisher exact test. F-statistics and STRUCTURE analysis based on the select different sets of SNPs were used to evaluate the effect of distinguishing the populations from HapMap Phase3. We found that randomly selected SNPs that were evenly distributed across the whole-genome were able to be used to identify the population structure. This study further indicated that more than 3 000 randomly selected SNPs that were evenly distributed across the whole-genome were substituted for AIMs in population stratification analysis, when there were no available AIMs for spe-cific populations.

  4. Variants in multiple genes polymorphism association analysis of COPD in the Chinese Li population

    PubMed Central

    Ding, Yipeng; Yang, Danlei; Zhou, Long; Xu, Junxu; Chen, Yu; He, Ping; Yao, Jinjian; Chen, Jiannan; Niu, Huan; Sun, Pei; Jin, Tianbo

    2015-01-01

    Background It is known that the contribution of risk alleles to chronic obstructive pulmonary disease (COPD) may vary between populations. Further, previous studies involving various ethnic groups have revealed associations between COPD and genetic polymorphisms in families with sequence similarity 13, member A (FAM13A), micro-RNA 2054 (MIR2054), SET domain containing protein 7 (SETD7), ring finger protein 150 (RNF150), hedgehog interacting protein (HHIP), and vascular endothelial growth factor A (VEGFA). Our objective was to explore the association between these gene polymorphism and COPD in members of Chinese Li minority population. Materials and methods The Chinese Li population case–control study was conducted to assess genetic associations with COPD risk. Seven single nucleotide polymorphisms (SNPs) located on chromosome 4, including FAM13A, MIR2054, SETD7, RNF150, and HHIP, and nine SNPs in the VEGFA gene were genotyped among 234 cases and 240 controls using Sequenom Mass-ARRAY® platform. Linkage disequilibrium (LD) analysis was performed using Haploview software and the associations of the SNP frequencies with COPD were analyzed using chi-square (χ2) tests, genetic models analysis, and haplotype analysis. Results By χ2 we found the minor allele “G” of rs17050782 was with increased COPD risk in allele model. In genetic models, we found the minor allele of rs7671167 (P=0.028 by dominant model) and rs17050782 (P=0.008 by recessive model) was associated with the increased risk of COPD disease. Likewise, an increased risk of developing COPD was associated with the “GGCGC” haplotype of VEGFA (odds ratio =1.48, 95% confidence interval =1.02–2.12, P=0.037). Conclusion Our results were the first time to reveal that SNPs from FAM13A (rs7671167), SETD7 (rs17050782), and a haplotype of VEGFA (“GGCGC”) are potential susceptibility loci associated with increased COPD risk in Chinese Li minority population. PMID:26251585

  5. Adjustment for population stratification via principal components in association analysis of rare variants.

    PubMed

    Zhang, Yiwei; Guan, Weihua; Pan, Wei

    2013-01-01

    For unrelated samples, principal component (PC) analysis has been established as a simple and effective approach to adjusting for population stratification in association analysis of common variants (CVs, with minor allele frequencies MAF > 5%). However, it is less clear how it would perform in analysis of low-frequency variants (LFVs, MAF between 1% and 5%), or of rare variants (RVs, MAF < 5%). Furthermore, with next-generation sequencing data, it is unknown whether PCs should be constructed based on CVs, LFVs, or RVs. In this study, we used the 1000 Genomes Project sequence data to explore the construction of PCs and their use in association analysis of LFVs or RVs for unrelated samples. It is shown that a few top PCs based on either CVs or LFVs could separate two continental groups, European and African samples, but those based on only RVs performed less well. When applied to several association tests in simulated data with population stratification, using PCs based on either CVs or LFVs was effective in controlling Type I error rates, while nonadjustment led to inflated Type I error rates. Perhaps the most interesting observation is that, although the PCs based on LFVs could better separate the two continental groups than those based on CVs, the use of the former could lead to overadjustment in the sense of substantial power loss in the absence of population stratification; in contrast, we did not see any problem with the use of the PCs based on CVs in all our examples.

  6. Population structure analysis and association mapping of blast resistance in indica rice (Oryza sativa L.) landraces.

    PubMed

    Wu, Y Y; He, J B; Li, A H; Fang, N Y; He, W W; Dang, L L; Zeng, G Y; Huang, J; Bao, Y M; Zhang, H S

    2016-08-12

    Rice blast caused by Magnaporthe oryzae is one of the most devastating rice diseases worldwide. To understand the genetic diversity of indica landrace accessions and identify simple sequence repeat (SSR) markers that are associated with blast resistance, a population of 276 indica landraces from across the world was constructed. This population was then used to evaluate the blast-resistance phenotype through artificial inoculation under controlled conditions in 2012 and 2013. The genetic diversity and association of the population with resistance were analyzed by examining the phenotype for 160 SSR markers distributed on 12 rice chromosomes. The 276 accessions were classified into seven groups using model- and distance-based cluster analyses. Associations between SSR markers and blast resistance showed that 26 SSR markers were significantly associated with blast resistance in 2012 and 2013 (P < 0.01) and that the phenotypic variation ranged from 2.68 to 13.11%. Nineteen of the markers associated with blast resistance were located in regions where genes or quantitative trait loci (QTLs) have been previously reported, and seven were newly identified in this study. These results indicate that marker-trait association has potential advantages over classical linkage analysis and QTL mapping, and that these markers could be used for marker-assisted selection in rice blast-resistance-breeding programs.

  7. Association analysis of ANK3 gene variants with schizophrenia in a northern Chinese Han population

    PubMed Central

    Guo, Xiaojuan; Zhang, Yani; Du, Jieli; Yang, Hua; Ma, Yini; Li, Jingjie; Yan, Mengdan; Jin, Tianbo; Liu, Xianyang

    2016-01-01

    Schizophrenia is a chronic, severely debilitating mental disorder. Many studies have suggested that genetic factors play an important role in the onset and development of schizophrenia. In our study, we conducted a case-control study in a northern Chinese Han population of 499 schizophrenia patients and 500 controls to investigate the effect of variant genotypes of 13 SNPs in ANK3 on schizophrenia risk. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the chi-squared test, genetic model analysis, and haplotype analysis. Four ANK3 SNPs were associated with schizophrenia risk. The minor allele of rs958852 in ANK3 was associated with a 0.75-fold reduction in schizophrenia risk in an allelic model. In the genetic model, rs958852 was associated with a reduced schizophrenia risk, and rs10994336, rs10994338 and rs4948418 were associated with an increased schizophrenia risk (rs10994336, OR = 2.00, 95%CI: 1.01–3.94, p = 0.047; rs10994338, OR = 1.99, 95%CI: 1.01–3.93, p = 0.047; rs4948418, OR = 2.00, 95%CI: 1.01–3.94, p = 0.047). In addition, haplotype “TTC” of ANK3 was associated with a 0.73-fold reduced schizophrenia risk (95%CI: 0.54–0.99; p = 0.044). To our knowledge, this is the first to report of an association between ANK3 rs10994336, rs10994338, rs4948418 and rs958852 and schizophrenia risk in a northern Chinese Han population. PMID:27811378

  8. Association Analysis of MET Gene Polymorphism with Papillary Thyroid Carcinoma in a Chinese Population

    PubMed Central

    Ning, Lifeng; Yu, Yaqin; Liu, Xiaoli; Ai, Lizhe; Zhang, Xin; Rao, Wenwang; Shi, Jieping; Sun, Hui; Yu, Qiong

    2015-01-01

    To investigate the association of MET SNPs with gender disparity in thyroid tumors, as well as the metastasis and prognosis of patients, 858 patients with papillary thyroid carcinoma (PTC), 556 patients with nodular goiter, and 896 population-based normal controls were recruited. The genotyping of MET SNPs was carried out using the Sequenom MassARRAY system. The distribution of MET SNPs (rs1621 and rs6566) was different among groups. Gender stratification analysis revealed a significant association between the rs1621 genotype and PTC in female patients (P = 0.037), but not in male patients (P > 0.05). For female patients, the rs1621 AG genotype was significantly higher in patients with PTC than in normal controls (P = 0.01) and revealed an increasing risk of PTC (OR: 1.465, 95% CI: 1.118–1.92). However, association analysis of the rs1621 genotype with metastasis and prognosis revealed no significant correlation in both male and female patients. The findings of our study showed that polymorphism of SNP locus rs1621 in MET gene may be associated with gender disparity in PTC. Higher AG genotypes in rs1621 were correlated with PTC in female patients, but not in male patients. PMID:26649038

  9. Association between childhood eczema and headaches: An analysis of 19 US population-based studies.

    PubMed

    Silverberg, Jonathan I

    2016-02-01

    Atopic dermatitis (or eczema) is a chronic inflammatory disorder associated with sleep disturbances and quality-of-life impairment. Sleep disturbances have been shown to cause headaches in childhood. However, an association between eczema and headaches is not well established. We sought to determine whether childhood eczema is associated with increased headaches and whether such association is related to fatigue or sleep disturbance. We analyzed data from 401,002 children and adolescents in 19 US population-based cross-sectional studies from the National Survey of Children's Health 2003/2004 and 2007/2008 and the National Health Interview Survey 1997-2013. In multivariate models controlling for age, sex, race/ethnicity, household income, highest level of education in the family, insurance coverage, number of persons in the household, birthplace in the United States, ever history of asthma, hay fever, and food allergy, eczema was found to be associated with headaches in 14 of 19 studies. In a pooled analysis of all 19 studies, children with eczema compared with those without eczema had a significantly higher prevalence (10.7% [95% CI, 10.3% to 11.0%] vs 5.4% [95% CI, 5.3% to 5.5%]) and odds (1.52 [95% CI, 1.45-1.59]) of headaches. Mild (1.79 [95% CI, 1.07-2.98]) and severe (2.72 [95% CI, 1.33-5.57]) eczema were associated with significantly higher odds of headaches. In particular, eczema associated with atopy, fatigue, excessive daytime sleepiness, insomnia, and only 0 to 3 nights of sufficient sleep had even higher odds of headache than eczema alone. Eczema is associated with increased headaches in childhood, particularly in patients with severe disease accompanied by atopy, fatigue, and sleep disturbances. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. Association between childhood eczema and headaches: An analysis of 19 US population-based studies

    PubMed Central

    Silverberg, Jonathan I.

    2016-01-01

    Background Atopic dermatitis (or eczema) is a chronic inflammatory disorder associated with sleep disturbances and quality-of-life impairment. Sleep disturbances have been shown to cause headaches in childhood. However, an association between eczema and headaches is not well established. Objectives We sought to determine whether childhood eczema is associated with increased headaches and whether such association is related to fatigue or sleep disturbance. Methods We analyzed data from 401,002 children and adolescents in 19 US population-based cross-sectional studies from the National Survey of Children’s Health 2003/2004 and 2007/2008 and the National Health Interview Survey 1997–2013. Results In multivariate models controlling for age, sex, race/ethnicity, household income, highest level of education in the family, insurance coverage, number of persons in the household, birthplace in the United States, ever history of asthma, hay fever, and food allergy, eczema was found to be associated with headaches in 14 of 19 studies. In a pooled analysis of all 19 studies, children with eczema compared with those without eczema had a significantly higher prevalence (10.7% [95% CI, 10.3% to 11.0%] vs 5.4% [95% CI, 5.3% to 5.5%]) and odds (1.52 [95% CI, 1.45–1.59]) of headaches. Mild (1.79 [95% CI, 1.07–2.98]) and severe (2.72 [95% CI, 1.33–5.57]) eczema were associated with significantly higher odds of headaches. In particular, eczema associated with atopy, fatigue, excessive daytime sleepiness, insomnia, and only 0 to 3 nights of sufficient sleep had even higher odds of headache than eczema alone. Conclusions Eczema is associated with increased headaches in childhood, particularly in patients with severe disease accompanied by atopy, fatigue, and sleep disturbances. PMID:26329510

  11. Association of carotid atherosclerosis and recurrent cerebral infarction in the Chinese population: a meta-analysis

    PubMed Central

    Liu, Jianping; Zhu, Yun; Wu, Yuhuai; Liu, Yan; Teng, Zhaowei; Hao, Yinglu

    2017-01-01

    Stroke, when poor blood flow to the brain results in cell death, is the third leading cause of disability and mortality worldwide, and appears as an unequal distribution in the global population. The cumulative risk of recurrence varies greatly up to 10 years after the first stroke. Carotid atherosclerosis is a major risk factor for stroke. The aim of this study was to investigate and estimate the relationship between carotid atherosclerosis and risk of stroke recurrence in the Chinese population. We performed a systematic review and meta-analysis of randomized controlled trials published from 2000 to 2013, using the following databases: PubMed, Embase, Medline, Wanfang, and the China National Knowledge Infrastructure. The odds ratios with 95% confidence intervals were calculated to examine this strength. A total of 22 studies, including 3,912 patients, 2,506 first-ever cases, and 1,406 recurrent cases, were pooled in this meta-analysis. Our results showed that the frequency of carotid atherosclerosis is higher in recurrent cases than that in the first-ever controls (78.88% vs 59.38%), and the statistical analysis demonstrated significant positive association between carotid atherosclerosis and recurrent cerebral infarction (odds ratio: 2.87; 95% confidence interval: 2.42–3.37; P<0.00001) in a fixed-effect model. No significant heterogeneity was observed across all studies. In conclusion, our results showed that carotid atherosclerosis was associated with increased risk of recurrent stroke. However, further well-designed research with large sample sizes is still needed to identify the clear mechanism. PMID:28260898

  12. Analysis of cystic fibrosis gene mutations and associated haplotypes in the Croatian population.

    PubMed

    Knezević, Jelena; Tanacković, Goranka; Matijević, Tanja; Barisić, Ingeborg; Pavelić, Jasminka

    2007-01-01

    The aim of this study was to reveal the CFTR gene mutation status in the Croatian population as well as to establish the haplotypes associated with cystic fibrosis (CF) and those associated with specific gene mutations. A total of 48 unrelated CF patients from Croatia were examined. Among 96 tested alleles, we found nine different mutations: DeltaF508, 58.33%; G542X, 3.12%; N1303K, 2.08%; R1162X; 621 + 1G --> T; G85E; Y569C; E585X; and S466X, 1.04%. Analysis of three polymorphic loci revealed 15 different haplotypes. Two of them (21-23-13 and 21-17-13) occurred with a higher frequency (40% and 24%). Both of these haplotypes also carried a CFTR gene mutation (DeltaF508 or G542X) on 27 out of 32 chromosomes. Among 12 (of all together 29) CF alleles on which no mutations were found, we detected 10 different haplotypes. Because there are still no published data on the distribution of polymorphic loci in Croatia, nor haplotypes associated with mutations in the CFTR gene, our results greatly contribute to knowledge regarding the genetic background of CF in this region.

  13. Exome-Wide Association Analysis of Coronary Artery Disease in the Kingdom of Saudi Arabia Population

    PubMed Central

    de Kovel, Carolien G.; Mulder, Flip; van Setten, Jessica; van ‘t Slot, Ruben; Al-Rubaish, Abdullah; Alshehri, Abdullah M.; Al Faraidy, Khalid; Al-Ali, Abdullah; Al-Madan, Mohammed; Al Aqaili, Issa; Larbi, Emmanuel; Al-Ali, Rudaynah; Alzahrani, Alhusain; Asselbergs, Folkert W.; Koeleman, Bobby P. C.; Al-Ali, Amein

    2016-01-01

    Coronary Artery Disease (CAD) remains the leading cause of mortality worldwide. Mortality rates associated with CAD have shown an exceptional increase particularly in fast developing economies like the Kingdom of Saudi Arabia (KSA). Over the past twenty years, CAD has become the leading cause of death in KSA and has reached epidemic proportions. This rise is undoubtedly caused by fast urbanization that is associated with a life-style that promotes CAD. However, the question remains whether genetics play a significant role and whether genetic susceptibility is increased in KSA compared to the well-studied Western European populations. Therefore, we performed an Exome-wide association study (EWAS) in 832 patients and 1,076 controls of Saudi Arabian origin to test whether population specific, strong genetic risk factors for CAD exist, or whether the polygenic risk score for known genetic risk factors for CAD, lipids, and Type 2 Diabetes show evidence for an enriched genetic burden. Our results do not show significant associations for a single genetic locus. However, the heritability estimate for CAD for this population was high (h2 = 0.53, S.E. = 0.1, p = 4e-12) and we observed a significant association of the polygenic risk score for CAD that demonstrates that the population of KSA, at least in part, shares the genetic risk associated to CAD in Western populations. PMID:26849363

  14. Association analysis of the RGS4 gene in Han Chinese and Scottish populations with schizophrenia.

    PubMed

    Zhang, F; St Clair, D; Liu, X; Sun, X; Sham, P C; Crombie, C; Ma, X; Wang, Q; Meng, H; Deng, W; Yates, P; Hu, X; Walker, N; Murray, R M; Collier, D A; Li, T

    2005-10-01

    We investigated the RGS4 as a susceptibility gene for schizophrenia in Chinese Han (184 trios and 138 sibling pairs, a total of 322 families) and Scottish (580 cases and 620 controls) populations using both a family trio and case-control design. Both the samples had statistical power greater than 70% to detect a heterozygote genotype relative risk of >1.2 for frequent RGS4-risk alleles. We genotyped four single nucleotide polymorphisms (SNPs) which have previously been associated with schizophrenia as either individually or part of haplotypes. Allele frequencies and linkage disequilibrium between the SNPs was similar in the two populations. In the Chinese sample, no individual SNPs or any of their haplotypes were associated with schizophrenia. In the Scottish population, one SNP (SNP7) was significantly over-represented in the cases compared with the controls (0.44 vs. 0.38; A allele; chi(2) 7.08, P = 0.011 after correction for correlation between markers by permutation testing). One two-marker haplotype, composed of alleles T and A of SNP4 and SNP7, respectively, showed individual significance after correction by permutation testing (chi(2) 6.8; P = 0.04). None of the full four-marker haplotypes showed association, including the G-G-G-G haplotype previously associated with schizophrenia in more than one sample and the A-T-A-A haplotype. Thus, our data do not directly replicate previous associations of RGS4, but association with SNP 7 in the Scottish population provides some support for a role in schizophrenia susceptibility. We cannot conclusively exclude RGS4, as associated haplotypes are likely to be surrogates for unknown causative alleles, whose relationship with overlying haplotypes may differ between the population groups. Differences in the association seen across the two populations could result from methodological factors such as diagnostic differences but most likely result from ethnic differences in haplotype structures within RGS4.

  15. A genome-wide analysis of population structure in the Finnish Saami with implications for genetic association studies

    PubMed Central

    Huyghe, Jeroen R; Fransen, Erik; Hannula, Samuli; Van Laer, Lut; Van Eyken, Els; Mäki-Torkko, Elina; Aikio, Pekka; Sorri, Martti; Huentelman, Matthew J; Camp, Guy Van

    2011-01-01

    The understanding of patterns of genetic variation within and among human populations is a prerequisite for successful genetic association mapping studies of complex diseases and traits. Some populations are more favorable for association mapping studies than others. The Saami from northern Scandinavia and the Kola Peninsula represent a population isolate that, among European populations, has been less extensively sampled, despite some early interest for association mapping studies. In this paper, we report the results of a first genome-wide SNP-based study of genetic population structure in the Finnish Saami. Using data from the HapMap and the human genome diversity project (HGDP-CEPH) and recently developed statistical methods, we studied individual genetic ancestry. We quantified genetic differentiation between the Saami population and the HGDP-CEPH populations by calculating pair-wise FST statistics and by characterizing identity-by-state sharing for pair-wise population comparisons. This study affirms an east Asian contribution to the predominantly European-derived Saami gene pool. Using model-based individual ancestry analysis, the median estimated percentage of the genome with east Asian ancestry was 6% (first and third quartiles: 5 and 8%, respectively). We found that genetic similarity between population pairs roughly correlated with geographic distance. Among the European HGDP-CEPH populations, FST was smallest for the comparison with the Russians (FST=0.0098), and estimates for the other population comparisons ranged from 0.0129 to 0.0263. Our analysis also revealed fine-scale substructure within the Finnish Saami and warns against the confounding effects of both hidden population structure and undocumented relatedness in genetic association studies of isolated populations. PMID:21150888

  16. A genome-wide analysis of population structure in the Finnish Saami with implications for genetic association studies.

    PubMed

    Huyghe, Jeroen R; Fransen, Erik; Hannula, Samuli; Van Laer, Lut; Van Eyken, Els; Mäki-Torkko, Elina; Aikio, Pekka; Sorri, Martti; Huentelman, Matthew J; Van Camp, Guy

    2011-03-01

    The understanding of patterns of genetic variation within and among human populations is a prerequisite for successful genetic association mapping studies of complex diseases and traits. Some populations are more favorable for association mapping studies than others. The Saami from northern Scandinavia and the Kola Peninsula represent a population isolate that, among European populations, has been less extensively sampled, despite some early interest for association mapping studies. In this paper, we report the results of a first genome-wide SNP-based study of genetic population structure in the Finnish Saami. Using data from the HapMap and the human genome diversity project (HGDP-CEPH) and recently developed statistical methods, we studied individual genetic ancestry. We quantified genetic differentiation between the Saami population and the HGDP-CEPH populations by calculating pair-wise F(ST) statistics and by characterizing identity-by-state sharing for pair-wise population comparisons. This study affirms an east Asian contribution to the predominantly European-derived Saami gene pool. Using model-based individual ancestry analysis, the median estimated percentage of the genome with east Asian ancestry was 6% (first and third quartiles: 5 and 8%, respectively). We found that genetic similarity between population pairs roughly correlated with geographic distance. Among the European HGDP-CEPH populations, F(ST) was smallest for the comparison with the Russians (F(ST)=0.0098), and estimates for the other population comparisons ranged from 0.0129 to 0.0263. Our analysis also revealed fine-scale substructure within the Finnish Saami and warns against the confounding effects of both hidden population structure and undocumented relatedness in genetic association studies of isolated populations.

  17. 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

  18. Population Structure, Genetic Diversity and Molecular Marker-Trait Association Analysis for High Temperature Stress Tolerance in Rice

    PubMed Central

    Barik, Saumya Ranjan; Sahoo, Ambika; Mohapatra, Sudipti; Nayak, Deepak Kumar; Mahender, Anumalla; Meher, Jitandriya; Anandan, Annamalai

    2016-01-01

    Rice exhibits enormous genetic diversity, population structure and molecular marker-traits associated with abiotic stress tolerance to high temperature stress. A set of breeding lines and landraces representing 240 germplasm lines were studied. Based on spikelet fertility percent under high temperature, tolerant genotypes were broadly classified into four classes. Genetic diversity indicated a moderate level of genetic base of the population for the trait studied. Wright’s F statistic estimates showed a deviation of Hardy-Weinberg expectation in the population. The analysis of molecular variance revealed 25 percent variation between population, 61 percent among individuals and 14 percent within individuals in the set. The STRUCTURE analysis categorized the entire population into three sub-populations and suggested that most of the landraces in each sub-population had a common primary ancestor with few admix individuals. The composition of materials in the panel showed the presence of many QTLs representing the entire genome for the expression of tolerance. The strongly associated marker RM547 tagged with spikelet fertility under stress and the markers like RM228, RM205, RM247, RM242, INDEL3 and RM314 indirectly controlling the high temperature stress tolerance were detected through both mixed linear model and general linear model TASSEL analysis. These markers can be deployed as a resource for marker-assisted breeding program of high temperature stress tolerance. PMID:27494320

  19. Population Structure, Genetic Diversity and Molecular Marker-Trait Association Analysis for High Temperature Stress Tolerance in Rice.

    PubMed

    Pradhan, Sharat Kumar; Barik, Saumya Ranjan; Sahoo, Ambika; Mohapatra, Sudipti; Nayak, Deepak Kumar; Mahender, Anumalla; Meher, Jitandriya; Anandan, Annamalai; Pandit, Elssa

    2016-01-01

    Rice exhibits enormous genetic diversity, population structure and molecular marker-traits associated with abiotic stress tolerance to high temperature stress. A set of breeding lines and landraces representing 240 germplasm lines were studied. Based on spikelet fertility percent under high temperature, tolerant genotypes were broadly classified into four classes. Genetic diversity indicated a moderate level of genetic base of the population for the trait studied. Wright's F statistic estimates showed a deviation of Hardy-Weinberg expectation in the population. The analysis of molecular variance revealed 25 percent variation between population, 61 percent among individuals and 14 percent within individuals in the set. The STRUCTURE analysis categorized the entire population into three sub-populations and suggested that most of the landraces in each sub-population had a common primary ancestor with few admix individuals. The composition of materials in the panel showed the presence of many QTLs representing the entire genome for the expression of tolerance. The strongly associated marker RM547 tagged with spikelet fertility under stress and the markers like RM228, RM205, RM247, RM242, INDEL3 and RM314 indirectly controlling the high temperature stress tolerance were detected through both mixed linear model and general linear model TASSEL analysis. These markers can be deployed as a resource for marker-assisted breeding program of high temperature stress tolerance.

  20. Analysis of the genetic association between IL27 variants and coronary artery disease in a Chinese Han population

    PubMed Central

    Fan, Qian; Nie, Shaofang; Li, Sihui; Liao, Yuhua; Zhang, Hongsong; Zha, Lingfeng; Wang, Fan; Tang, Tingting; Xia, Ni; Xu, Chengqi; Wang, Pengyun; Xie, Tian; Xie, Jiangjiao; Lu, Qiulun; Li, Qingxian; Qian, Jin; Li, Bin; Wu, Gang; Wu, Yanxia; Yang, Yan; Wang, Qing K.; Tu, Xin; Cheng, Xiang

    2016-01-01

    Interleukin-27 (IL-27) is an important cytokine in inflammatory diseases, including coronary artery disease (CAD). To explore the precise role of IL-27 in CAD, we investigated the genetic association between IL27 and CAD in the GeneID Chinese Han population. A two-stage case control association analysis was performed for 3075 CAD cases and 2802 controls. Logistic regression analysis was used to adjust the traditional risk factors for CAD. Results showed that a promoter variant, rs153109, tended to be marginally associated with CAD in the discovery population (Padj = 0.028, OR = 1.27, 95%CI: 1.03–1.58). However, this association was not replicated in the validation stage (Padj = 0.559, OR = 1.04, 95%CI: 0.90–1.21). In addition, when we classified the combined population into two subgroups according to the age at disease onset or disease state, we again obtained no significant associations. Finally, we estimated the severity of coronary stenosis using the Gensini Scoring system and determined that the rs153109 genotypes were still not associated with the Gensini scores of the CAD patients. In conclusion, our study failed to find an association between common variants in the functional region of IL27 and CAD in a Chinese Han population, which indicated that IL-27 might only be an inflammatory marker during the development of CAD. PMID:27174010

  1. Association analysis of GWAS and candidate gene loci in a Pakistani population with psoriasis.

    PubMed

    Munir, Saeeda; ber Rahman, Simeen; Rehman, Sadia; Saba, Nusrat; Ahmad, Wasim; Nilsson, Staffan; Mazhar, Kehkashan; Naluai, Åsa Torinsson

    2015-03-01

    Psoriasis is a common inflammatory and hyper proliferative condition of the skin and a serious chronic systemic autoimmune disease. We undertook an association study to investigate the genetic etiology of psoriasis in a Pakistani population by genotyping single-nucleotide polymorphisms (SNPs) previously reported to be associated in genome-wide association (GWAS) or in candidate gene studies of psoriasis. Fifty seven single-nucleotide polymorphisms (SNPs) from 42 loci were genotyped in 533 psoriasis patients and 373 controls. Our results showed genome wide significant association of the MHC region (rs1265181 being the most significant from five SNPs used with overall OR=3.38; p=2.97E-18), as well as nominally significant associations at ten other loci (p<0.05) in the Pakistani population (LCE3B, REL, IL13/IL4, TNIP1, IL12B, TRAF3IP2, ZC3H12C, NOS2 and RNF114 from GWAS and PRR9 from a previous candidate gene study). Overall, only nine SNPs out of the 42 GWAS loci, displayed an odds ratio in the opposite allelic direction and only three did not reach similar odds ratio within 95% confidence interval as previously reported (SLC45A1/TNFRSF9, ELMO1 and IL28RA). This indicates similar genetic risk factors and molecular mechanisms behind disease in Pakistani psoriasis patients as in other populations. In addition, we show that the MHC and TNIP1 regions are significantly different in patients with psoriasis onset before the age of 40 (type I) compared to after 40 years of age (type II). MHC being associated mainly with type I while TNIP1 with type II patients.

  2. Genetic association of RIT2 rs12456492 polymorphism and Parkinson's disease susceptibility in Asian populations: a meta-analysis.

    PubMed

    Lu, Yanjun; Liu, Wei; Tan, Kun; Peng, Jing; Zhu, Yaowu; Wang, Xiong

    2015-09-03

    Recent studies investigating the association of the Ras-like without CAAX 2 (RIT2) polymorphism, rs12456492, with Parkinson's disease (PD) are controversial. We performed a meta-analysis to study the association between rs12456492 and PD susceptibility in Asian populations. Literature searches of PubMed and Embase were performed up to June 3, 2015, and the strength of the association between rs12456492 and PD was evaluated by odds ratios (OR) and 95% confidence intervals (CI). Four studies conducted between 2013 and 2015, comprising 2017 PD cases and 2010 controls, were included in the meta-analysis. Significant association of rs12456492 with PD was found in the dominant (GG + AG vs. AA: OR = 1.26, 95% CI = 1.20-1.44, P = 0.00) and additive models (GG vs. AA: OR = 1.38, 95% CI = 1.03-1.83, P = 0.030). Although sensitivity analysis found that the overall result was stable only in the dominant genetic model, a publication bias was also detected. Therefore, the results should be treated with caution. The current meta-analysis suggested that rs12456492 might be associated with increased PD risk in Asian populations, but studies using larger sample sizes and different ethnic populations will be needed to further confirm this association.

  3. Genetic Association Analysis of Common Variants in FOXO3 Related to Longevity in a Chinese Population

    PubMed Central

    Yan, Dongjing; Liao, Xiaoping; Wang, Xianshou; Fu, Yunxin; Cai, Wangwei

    2016-01-01

    Recent studies suggested that forkhead box class O3 (FOXO3) functions as a key regulator for the insulin/insulin-like growth factor-1signaling pathway that influence aging and longevity. This study aimed to comprehensively elucidate the association of common genetic variants in FOXO3 with human longevity in a Chinese population. Eighteen single-nucleotide polymorphisms (SNPs) in FOXO3 were successfully genotyped in 616 unrelated long-lived individuals and 846 younger controls. No nominally significant effects were found. However, when stratifying by gender, four SNPs (rs10499051, rs7762395, rs4946933 and rs3800230) previously reported to be associated with longevity and one novel SNP (rs4945815) showed significant association with male longevity (P-values: 0.007–0.032), but all SNPs were not associated with female longevity. Correspondingly, males carrying the G-G-T-G haplotype of rs10499051, rs7762395, rs4945815 and rs3800230 tended to have longer lifespan than those carrying the most common haplotype A-G-C-T (odds ratio = 2.36, 95% confidence interval = 1.20–4.63, P = 0.013). However, none of the associated SNPs and haplotype remained significant after Bonferroni correction. In conclusion, our findings revealed that the FOXO3 variants we tested in our population of Chinese men and women were associated with longevity in men only. None of these associations passed Bonferroni correction. Bonferroni correction is very stringent for association studies. We therefore believe the effects of these nominally significant variants on human longevity will be confirmed by future studies. PMID:27936216

  4. Association between 12p13 SNP rs11833579 and ischemic stroke in Asian population: An updated meta-analysis.

    PubMed

    Wang, Ling; Zhao, Chi; Xia, Qing-Xin; Qiao, Si-Jie

    2014-10-15

    A GWAS found that the single-nucleotide polymorphism rs11833579 near the NINJ2 gene on chromosome 12p13 was associated with an increased risk of ischemic stroke in Caucasians in 2009. Several studies have been carried out to explore the association between this SNP and ischemic stroke in Asians, but published results were contradictory. In the present study, we performed a meta-analysis to further evaluate this association in the Asian population. All relevant articles were retrieved from the databases of PubMed, EMBASE, Chinese Biomedical Literature Database, CNKI, CQVIP, and WANFANG Database from the establishment date to February 2014. Statistical analyses were performed by using Stata 11. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of the association. Possible publication bias was checked by funnel plots, Begg's test and Egger's test. Eleven studies were eligible for meta-analysis including 9358 cases and 8936 controls. Overall, there were no significant associations between rs11833579 and ischemic stroke under the allelic (OR=0.963, 95% CI: 0.850-1.092, p=0.559), dominant (OR=0.946, 95% CI: 0.778-1.150, p=0.580), recessive (OR=0.993, 95% CI: 0.914-1.078, p=0.868), and homozygote (OR=0.968, 95% CI: 0.796-1.177, p=0.744) genetic models in the Asian population. Further, we found no evidence of association of rs11833579 with large artery atherosclerosis (LAA) or small-artery occlusion (SAO) stroke in all genetic models. The results of the subgroup analysis for Chinese population and Japanese population were consistent with that of the overall study. Our meta-analysis shows that SNP rs11833579 is not related to ischemic stroke in the Asian population. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Association between the interleukin-1β C-511T polymorphism and periodontitis: a meta-analysis in the Chinese population.

    PubMed

    Wang, H F; He, F Q; Xu, C J; Li, D M; Sun, X J; Chi, Y T; Guo, W

    2017-02-23

    The association between the interleukin-1 beta (IL-1β) C-511T (or rs16944) polymorphism and periodontitis remains inconclusive, even though there have been previous studies on this association. To assess the effects of IL-1β C-511T variants on the risk of development of periodontitis, a meta-analysis was performed in a single ethnic population. Studies, published up to December 2015, were selected for the meta-analysis from PubMed and Chinese databases. The associations were assessed with pooled OR and 95%CI. This meta-analysis identified 8 studies, including 1276 periodontitis cases and 1558 controls. Overall, a significant association between the IL-1β C-511T polymorphism and periodontitis was found in the Chinese population (TT vs CC: OR = 1.48, 95%CI = 1.19-1.85; TT + CT vs CC: OR = 1.50, 95%CI = 1.25-1.81; T vs C: OR = 1.33, 95%CI = 1.06-1.68). In the subgroup analyses based on geographical area(s), source of controls, and type of periodontitis, significant results were obtained for the association between IL-1β C-511T variants and periodontitis. Our meta-analysis indicated that the IL-1β C-511T polymorphism may be a genetic susceptibility factor for periodontitis in the Chinese population. This marker could be used to identify Chinese individuals at a high risk for periodontitis.

  6. Early childhood measles vaccinations are not associated with paediatric IBD: a population-based analysis.

    PubMed

    Shaw, Souradet Y; Blanchard, James F; Bernstein, Charles N

    2015-04-01

    Early childhood vaccinations have been hypothesized to contribute to the emergence of paediatric inflammatory bowel disease [IBD] in developed countries. Using linked population-based administrative databases, we aimed to explore the association between vaccination with measles-containing vaccines and the risk for IBD. This was a case-control study using the University of Manitoba IBD Epidemiology Database [UMIBDED]. The UMIBDED was linked to the Manitoba Immunization Monitoring System [MIMS], a population-based database of immunizations administered in Manitoba. All paediatric IBD cases in Manitoba, born after 1989 and diagnosed before March 31, 2008, were included. Controls were matched to cases on the basis of age, sex, and region of residence at time of diagnosis. Measles-containing vaccinations received in the first 2 years of life were documented, with vaccinations categorized as 'None' or 'Complete', with completeness defined according to Manitoba's vaccination schedule. Conditional logistic regression models were fitted to the data, with models adjusted for physician visits in the first 2 years of life and area-level socioeconomic status at case date. A total of 951 individuals [117 cases and 834 controls] met eligibility criteria, with average age of diagnosis among cases at 11 years. The proportion of IBD cases with completed vaccinations was 97%, compared with 94% of controls. In models adjusted for physician visits and area-level socioeconomic status, no statistically significant association was detected between completed measles vaccinations and the risk of IBD (adjusted odds ratio [AOR]: 1.5; 95% confidence interval [CI]: 0.5-4.4; p = 0.419]. No significant association between completed measles-containing vaccination in the first 2 years of life and paediatric IBD could be demonstrated in this population-based study. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For

  7. An epigenome-wide association analysis of cardiac autonomic responses among a population of welders

    PubMed Central

    Zhang, Jinming; Liu, Zhonghua; Umukoro, Peter E.; Cavallari, Jennifer M.; Fang, Shona C.; Weisskopf, Marc G.; Lin, Xihong; Mittleman, Murray A.

    2017-01-01

    ABSTRACT DNA methylation is one of the potential epigenetic mechanisms associated with various adverse cardiovascular effects; however, its association with cardiac autonomic dysfunction, in particular, is unknown. In the current study, we aimed to identify epigenetic variants associated with alterations in cardiac autonomic responses. Cardiac autonomic responses were measured with two novel markers: acceleration capacity (AC) and deceleration capacity (DC). We examined DNA methylation levels at more than 472,506 CpG probes through the Illumina Infinium HumanMethylation450 BeadChip assay. We conducted separate linear mixed models to examine associations of DNA methylation levels at each CpG with AC and DC. One CpG (cg26829071) located in the GPR133 gene was negatively associated with DC values after multiple testing corrections through false discovery rate. Our study suggests the potential functional importance of methylation in cardiac autonomic responses. Findings from the current study need to be replicated in future studies in a larger population. PMID:28075199

  8. Genetic distribution and association analysis of DRD2 gene polymorphisms with major depressive disorder in the Chinese Han population.

    PubMed

    He, Mei; Yan, Hong; Duan, Zhao-Xia; Qu, Wei; Gong, Hai-Yan; Fan, Zheng-Li; Kang, Jian-Yi; Li, Bing-Cang; Wang, Jian-Min

    2013-01-01

    Dopamine D2 receptor is involved in reward-mediating mesocorticolimbic pathways. It plays an important role in major depressive disorder (MDD). Three gene polymorphisms Taq1A, C957T and -141C ins/del, were identified in the DRD2 gene among the Western population. These variants in the DRD2 gene might be associated with the susceptibility of MDD patients through affecting the bioeffects of endogenous dopamine neurotransmission. However, little is known about their occurrence in Chinese population and their association with the susceptibility of patients with major depressive disorder. In this study, a total of 338 unrelated adult Chinese Han population, including 224 healthy volunteers and 114 patients with major depressive disorder, were recruited. DRD2 polymorphisms (Taq1A and -141C ins/del) were detected using restriction fragment length polymorphism (RFLP) analysis and the C957T were detected by sequencing directly. As a result, three polymorphisms were identified in Chinese Han population and all were common SNP. However, we could detect no evidence of genetic association between 3 markers in DRD2 and major depressive disorder in the Chinese Han population. To conclude, this result suggests that Taq1A, C957T and -141C ins/del of DRD2 gene may not be associated with major depressive disorder, also may be the sample sizes too small to allow a meaningful test.

  9. Analysis of genetic polymorphisms associated with leukoaraiosis in the southern Chinese population

    PubMed Central

    Huang, Wen-Qing; Ye, Hui-Ming; Li, Fang-Fang; Yi, Ke-Hui; Zhang, Ya; Cai, Liang-Liang; Lin, Hui-Nuan; Lin, Qing; Tzeng, Chi-Meng

    2016-01-01

    Abstract Leukoaraiosis (LA) is a frequent neuroimaging finding commonly observed on brain MRIs of elderly people with prevalence ranging from 50% to 100%. Multiple susceptibility genes or genetic risk factors for LA have been identified in subjects of European descent. Here, we report the first replication study on several common and novel genetic variations in the Chinese population. In this study, a total of 244 subjects (201 LA patients and 43 controls) were enrolled according to our new and strict definition for LA. Subsequently, 6 genetic variants at 5 genes, rs3744028 in TRIM65, rs1055129 in TRIM47, rs1135889 in FBF1, rs1052053 in PMF1, and rs1801133 (C677T) and rs1801131(A1298C) in MTHFR, were selected for genotyping using polymerase chain reaction (PCR)-based pyrosequencing and restriction fragment length polymorphism (RFLP) together with capillary electrophoresis (CE) and agarose gel electrophoresis. Finally, Pearson's χ2 and multivariate logistic regression tests were used to examine the associations between the genotypes and LA. Among these candidate polymorphisms, except for rs1052053 and rs1801131, rs1135889 (P = 0.012) showed significant associations with LA in the dominant model, and the other 3 SNPs, rs3744028 (P = 0.043), rs1055129 (P = 0.038), and rs1801133 (P = 0.027), showed significant associations with LA in the recessive model. However, these differences no longer remained significant after adjusting for age, gender, hypertension, and diabetes mellitus and applying Bonferroni correction or Sidak correction for multiple testing. These results suggest that the above-mentioned genetic variants are not associated with LA risk. In summary, the study did not replicate the susceptibility of rs3744028, rs1055129, and rs1135889 at the Chr17q25 locus for LA nor did it find any other significant results for rs1052053, rs1801133, and rs1801131 in the Chinese population. It strongly indicated the ethnic differences in the genetics of LA

  10. Association analysis of historical bread wheat germplasm using additive genetic covariance of relatives and population structure.

    PubMed

    Crossa, José; Burgueño, Juan; Dreisigacker, Susanne; Vargas, Mateo; Herrera-Foessel, Sybil A; Lillemo, Morten; Singh, Ravi P; Trethowan, Richard; Warburton, Marilyn; Franco, Jorge; Reynolds, Matthew; Crouch, Jonathan H; Ortiz, Rodomiro

    2007-11-01

    Linkage disequilibrium can be used for identifying associations between traits of interest and genetic markers. This study used mapped diversity array technology (DArT) markers to find associations with resistance to stem rust, leaf rust, yellow rust, and powdery mildew, plus grain yield in five historical wheat international multienvironment trials from the International Maize and Wheat Improvement Center (CIMMYT). Two linear mixed models were used to assess marker-trait associations incorporating information on population structure and covariance between relatives. An integrated map containing 813 DArT markers and 831 other markers was constructed. Several linkage disequilibrium clusters bearing multiple host plant resistance genes were found. Most of the associated markers were found in genomic regions where previous reports had found genes or quantitative trait loci (QTL) influencing the same traits, providing an independent validation of this approach. In addition, many new chromosome regions for disease resistance and grain yield were identified in the wheat genome. Phenotyping across up to 60 environments and years allowed modeling of genotype x environment interaction, thereby making possible the identification of markers contributing to both additive and additive x additive interaction effects of traits.

  11. 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.

  12. Analysis of population genetic structure from Bucaramanga (Colombia) based on gene polymorphisms associated with the regulation of blood pressure

    PubMed Central

    Rondón, Fernando; Vargas, Clara Inés; Oróstegui, Myriam; Bautista, Leonelo; Serrano, Norma Cecilia; Páez, María c; Castillo, Adriana

    2012-01-01

    Introduction: In spite of nearly 40% of variability in blood pressure being explained by genetic factors, the identification of genes associated with essential high blood pressure is difficult to determine in populations where individuals have different genetic backgrounds. In these circumstances it is necessary to determinate whether the population is sub-structured because this can bias studies associated with this disease. Objective: To determine the genetic structure of the population in Bucaramanga from genetic polymorphisms associated with the regulation of blood pressure: 448G>T, 679C>T y 1711C>T from the gene kinase 4 of the dopaminergic receptor linked to the protein G and Glu298Asp, -786T>C and the VNTR of the intron 4 of the gene of endothelial nitric oxide. Methods: A sample of 552 unrelated individuals was studied through analysis of restriction fragment length polymorphism. The allelic, haplotypic and genotypic frequencies were calculated, the Hardy-Weinberg equilibrium was determined and a molecular analysis of variance was performed to determine the genetic structure. Results: Thirty-eight (38) Haplotypes were identified with GCCTG4b being the most frequent (21.2%). The most diverse polymorphism was 448G>T with a frequency of 49.9% for heterozygous. The six polymorphisms were found in genetic equilibrium and a genetic structure of populations was not evidenced (FST= 0.0038). Conclusion: The population studied does not present a genetic sub-structure and the polymorphisms analyzed were found in genetic equilibrium. This indicates that the population mixes randomly and there are no sub-groups capable of affecting the results of the association studies. PMID:24893057

  13. Analysis of HLA-DP association with beryllium disease susceptibility in pooled exposed populations

    SciTech Connect

    Cesare Saltini, Massimo Amicosante

    2009-12-19

    in each immunogenetic study. In this context, the populations of the study already performed in this field by the University of Modena and Rome (by Prof. C. Saltini) and the University of Pennsylvania (by Prof. M. Rossman) have been evaluated by using similar HLA molecular typing methodologies and that both populations have now been followed up for a period of 4 to 7 years. The general objective of this study has to generate a larger data base comprising the two population with which analyze gene disease association with greater statistical power and ascertain the effect of lesser common gener variants which may be missed when analyzing associations on small populations. In particular addressing the role suggested in previous study such as: (1) the role of HLA-DP rare alleles and polymorphisms, and (2) the role of the HLA markers in disease progression from sensitization. The two populations from the already published studies (Saltini et al Eur Respir J. 2001 18:677-84; Rossman et al Am J Respir Crit Care Med. 2002 165:788-94) present similar aspects about: ethnicity, type and length of exposure to Be dust, a broadly similar association between beryllium related abnormalities and HLA. The two population have been pooled and evaluated using common criteria of diagnosis (Sensitized subject: at least 2 positive BeLPT tests each with 2 positive wells; CBD-affected subject: identification of well formed non-caseating granulomas on biopsy), follow up and HLA typing technique (complete HLA-DRB, DQB, DPB high resolution typing using amplification with sequence specific primers or sequence based typing). The two populations included 137 subjects with Beryllium hypersensitized (BH) and 155 Be-exposed controls. Inclusion criteria were met by one hundred and six subjects with Be-hypersensitivity of whom 55 were affected by CBD (age 52 {+-} 11 years; 50 caucasians, 2 African-Americans 2 Hispanics and 1 Asian; 46 males and 9 females; mean duration of Be-exposure 15 {+-} 9 years

  14. Association of educational status with heart rate recovery: a population-based propensity analysis.

    PubMed

    Shishehbor, Mehdi H; Baker, David W; Blackstone, Eugene H; Lauer, Michael S

    2002-12-01

    An abnormally attenuated heart rate recovery after exercise is a predictor of mortality that is thought to reflect decreased parasympathetic activity. Lower educational level may be associated with automatic imbalance. We sought to assess the association of educational level with heart rate recovery. Among 5246 healthy adults from a population-based cohort who underwent exercise testing, 874 (17%) did not graduate from high school, 1823 (35%) completed high school, and 2549 (49%) attended at least some college. An abnormal heart rate recovery was defined as a difference of associated with an abnormal heart rate recovery (OR = 1.9; 95% CI: 1.6 to 2.4; P <0.001). During 12-years of follow-up, there were 327 deaths. Poor educational status was associated with greater mortality (9% [80/874] vs. 6% [247/4372]; unadjusted hazard ratio [HR] = 1.9; 95% CI: 1.4 to 2.5; P <0.001). However, after accounting for age, sex, and heart rate recovery, educational status was a weaker predictor (HR = 1.3; 95% CI: 1.0 to 1.7). Educational status is independently associated with an abnormal heart rate recovery.

  15. Association analysis of DISC1 gene polymorphisms with Attention-Deficit Hyperactivity Disorder in Iranian population.

    PubMed

    Kayyal, Matin; Movafagh, Abolfazl; Hashemi, Mehrdad; Sayad, Arezou; Emamalizadeh, Babak; PourIran, Khashayar; Kayyal, Mohammadmoien; Amirabadi, Mohammad Reza Eslami; Zamani, Mahdi; Darvish, Hossein

    2015-01-01

    Attention deficit hyperactivity disorder (ADHD) is a common heritable psychiatric disorder with a worldwide prevalence of 5%. The etiology of ADHD is still incompletely understood, but several studies, consistently indicate the strong role of genetic factors on this disorder. The aim of this study was to determine the effect of three SNPs rs11122319, rs11122330 and rs6675281 in the etiology of ADHD in an Iranian children. In this research work, for the first time, we investigated the association of three SNPs (rs11122330, rs6675281 and rs11122319) in the DISC1 gene with ADHD in Iranian population. Two hundred fourthy subjects composed of 120 patients and 120 healthy controls were included and tetra-primer ARMS PCR technique was used for genotyping all selected SNPs. We found differences in genotype and allele distributions of rs 6675281 polymorphism between our patients and controls. The A, T and A alleles were the more frequent alleles in rs11122319, rs6675281 and rs11122330 polymorphisms in both case and control groups respectively. The TT genotype was more frequent in control group compared to patients. (P value = 0.008, OR= 1.5837, 95% CI= 1.1012 to 2.2776). Our findings strengthens the role of DISC1 gene as a susceptibility locus for ADHD and indicate that rs6675281 polymorphism is a susceptibility factor for ADHD for the first time in children reported in an Iranian population in this part of the world.

  16. Is Statin Use Associated With Tendon Rupture? A Population-Based Retrospective Cohort Analysis.

    PubMed

    Contractor, Tahmeed; Beri, Abhimanyu; Gardiner, Joseph C; Tang, Xiaoqin; Dwamena, Francesca C

    2015-01-01

    Previous case reports and small studies have suggested that 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (HMG-CoA-Is) may increase the risk of tendon rupture. We conducted a population-based retrospective cohort evaluation to better assess this relationship. From approximately 800,000 enrollees of a private insurance database, those who were aged ≤64 years with at least 1 year of continuous enrollment were selected. Exposure was defined as initiation of HMG-CoA-I after the beginning of the study period. Each exposed person was matched with 2 controls of similar age and gender. Baseline characteristics, including known risk factors for tendon rupture, were compared between exposed and control cohorts with fidelity to the study's matched design. After adjusting for differences in follow-up and baseline characteristics, incidence rate ratios for tendon rupture was assessed in HMG-CoA-I users and nonusers. A total of 34,749 exposed patients were matched with 69,498 controls. There was no difference in the occurrence of tendon ruptures in HMG-CoA-I users versus nonusers. The results remained unchanged after adjustment for age and gender. In conclusion, this population-based retrospective cohort evaluation suggests that use of HMG-CoA-Is as a group are not associated with tendon rupture.

  17. Statistical analysis of submarine fault populations associated with oceanic transform boundaries

    NASA Astrophysics Data System (ADS)

    Morrow, T. A.; Mittelstaedt, E. L.; Harpp, K.; Soule, S. A.

    2012-12-01

    Oceanic transform boundaries exhibit fault populations with strikingly different morphologies. Statistical analysis of these fault populations is a useful tool for investigating crustal strain, fault growth, and the regional stress field of the lithosphere (i.e., transpressional, transtensional, or strike slip). Achieving reliable statistics, however, requires the identification of numerous fault traces followed by accurate and precise measurements of the length, throw, and heave along each member of the fault set. Current methodologies for fault measurement from bathymetric data often require picking the tops and bottoms of digitized fault scarps by hand. This method is time-consuming for large fault populations and may be subject to expectation bias in measurements; consequently, it is difficult to make consistent interpretations of fault lineaments, particularly when dealing with large fault populations. Another method for gathering fault statistics from the seafloor uses binarized sidescan sonar data to identify fault traces and to measure fault heave. Fault throw is then calculated using a regional average fault dip, assuming that local variations in fault geometries are small. Sidescan methods are limited by the instrument's look direction, which can place fault scarps in shadow, producing significant variability in the apparent heave. We present a new computational method that measures observable fault heave and throw from high-resolution multibeam bathymetric data. The code first constructs a series of linear bathymetric transects orthogonal to fault strike. The top and bottom of each fault scarp are defined along these transects as the nearest local minima in the absolute value of the bathymetric gradient. Finally, a median filter is applied to the locations of the resulting fault bounding points to remove noise and erroneous values. Our method improves on previous techniques by allowing an automated, unbiased measure of heave and throw along every

  18. Modeling association among demographic parameters in analysis of open population capture-recapture data

    USGS Publications Warehouse

    Link, William A.; Barker, Richard J.

    2005-01-01

    We present a hierarchical extension of the Cormack–Jolly–Seber (CJS) model for open population capture–recapture data. In addition to recaptures of marked animals, we model first captures of animals and losses on capture. The parameter set includes capture probabilities, survival rates, and birth rates. The survival rates and birth rates are treated as a random sample from a bivariate distribution, thus the model explicitly incorporates correlation in these demographic rates. A key feature of the model is that the likelihood function, which includes a CJS model factor, is expressed entirely in terms of identifiable parameters; losses on capture can be factored out of the model. Since the computational complexity of classical likelihood methods is prohibitive, we use Markov chain Monte Carlo in a Bayesian analysis. We describe an efficient candidate-generation scheme for Metropolis–Hastings sampling of CJS models and extensions. The procedure is illustrated using mark-recapture data for the moth Gonodontis bidentata.

  19. The association between HDAC9 gene polymorphisms and stroke risk in the Chinese population: A meta-analysis

    PubMed Central

    Zhou, Xin; Guan, Tangming; Li, Shuyuan; Jiao, Zinan; Lu, Xiaoshuang; Huang, Xiaodi; Ji, Yuhua; Ji, Qiuhong

    2017-01-01

    Several recent genome-wide association studies (GWASs) have suggested that the histone deacetylase 9 (HDAC9) gene is associated with stroke, but the reliability of these findings remains controversial, particularly for the data derived from different ethnicities and geographical locations. Therefore, we performed a meta-analysis to explore the associations between HDAC9 polymorphisms and the risk of stroke in the Chinese population. All eligible case-control studies that met the search criteria were retrieved from multiple databases, and six case-control studies with a total of 2,356 stroke patients and 3,420 healthy controls were included. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the strengths of the associations of 3 HDAC9 gene polymorphisms with stroke risk. Our results revealed statistically significant associations of the rs2107595 (T/C) polymorphism with an increased risk of stroke in the allele, codominant and dominant models. Additionally, the rs2389995 (G/A) polymorphism was found to be significantly associated with a decreased risk of stroke in all genetic models. In conclusion, this meta-analysis suggested that the T allele of rs2107595 in HDAC9 increases the risk of stroke but that the G allele of rs2389995 decreases the risk of stroke in the Chinese population. PMID:28145521

  20. Pathway Analysis for Genome-Wide Association Study of Lung Cancer in Han Chinese Population

    PubMed Central

    Wu, Chen; Jin, Guangfu; Dai, Juncheng; Wang, Cheng; Hu, Lingmin; Gou, Jianwei; Qian, Chen; Bai, Jianling; Wu, Tangchun; Hu, Zhibin; Lin, Dongxin; Shen, Hongbing; Chen, Feng

    2013-01-01

    Genome-wide association studies (GWAS) have identified a number of genetic variants associated with lung cancer risk. However, these loci explain only a small fraction of lung cancer hereditability and other variants with weak effect may be lost in the GWAS approach due to the stringent significance level after multiple comparison correction. In this study, in order to identify important pathways involving the lung carcinogenesis, we performed a two-stage pathway analysis in GWAS of lung cancer in Han Chinese using gene set enrichment analysis (GSEA) method. Predefined pathways by BioCarta and KEGG databases were systematically evaluated on Nanjing study (Discovery stage: 1,473 cases and 1,962 controls) and the suggestive pathways were further to be validated in Beijing study (Replication stage: 858 cases and 1,115 controls). We found that four pathways (achPathway, metPathway, At1rPathway and rac1Pathway) were consistently significant in both studies and the P values for combined dataset were 0.012, 0.010, 0.022 and 0.005 respectively. These results were stable after sensitivity analysis based on gene definition and gene overlaps between pathways. These findings may provide new insights into the etiology of lung cancer. PMID:23469231

  1. Phylogenetic analysis of actinobacterial populations associated with Antarctic Dry Valley mineral soils.

    PubMed

    Babalola, Olubukola O; Kirby, Bronwyn M; Le Roes-Hill, Marilize; Cook, Andrew E; Cary, S Craig; Burton, Stephanie G; Cowan, Don A

    2009-03-01

    Despite the apparent severity of the environmental conditions in the McMurdo Dry Valleys, Eastern Antarctica, recent phylogenetic studies conducted on mineral soil samples have revealed the presence of a wide diversity of microorganisms, with actinobacteria representing one of the largest phylotypic groups. Previous metagenomic studies have shown that the majority of Antarctic actinobacterial populations are classified as 'uncultured'. In this study, we assessed the diversity of actinobacteria in Antarctic cold desert soils by complementing traditional culture-based techniques with a metagenomic study. Phylogenetic analysis of clones generated with actinobacterium- and streptomycete-specific PCR primers revealed that the majority of the phylotypes were most closely related to uncultured Pseudonocardia and Nocardioides species. Phylotypes most closely related to a number of rarer actinobacteria genera, including Geodermatophilus, Modestobacter and Sporichthya, were also identified. While complementary culture-dependent studies isolated a number of Nocardia and Pseudonocardia species, the majority of the cultured isolates (> 80%) were Streptomyces species--although phylotypes affiliated to the genus Streptomyces were detected at a low frequency in the metagenomic study. This study confirms that Antarctic Dry Valley desert soil harbours highly diverse actinobacterial communities and suggests that many of the phylotypes identified may represent novel, uncultured species.

  2. Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci.

    PubMed

    Tanskanen, Tomas; van den Berg, Linda; Välimäki, Niko; Aavikko, Mervi; Ness-Jensen, Eivind; Hveem, Kristian; Wettergren, Yvonne; Bexe Lindskog, Elinor; Tõnisson, Neeme; Metspalu, Andres; Silander, Kaisa; Orlando, Giulia; Law, Philip J; Tuupanen, Sari; Gylfe, Alexandra E; Hänninen, Ulrika A; Cajuso, Tatiana; Kondelin, Johanna; Sarin, Antti-Pekka; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Järvinen, Heikki; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A; Palles, Claire; Martin, Lynn; Barclay, Ella; Tenesa, Albert; Farrington, Susan; Timofeeva, Maria N; Meyer, Brian F; Wakil, Salma M; Campbell, Harry; Smith, Christopher G; Idziaszczyk, Shelley; Maughan, Tim S; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D; Win, Aung K; Hopper, John; Jenkins, Mark; Newcomb, Polly A; Gallinger, Steve; Conti, David; Schumacher, Fredrick R; Casey, Graham; Cheadle, Jeremy P; Dunlop, Malcolm G; Tomlinson, Ian P; Houlston, Richard S; Palin, Kimmo; Aaltonen, Lauri A

    2017-09-28

    Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer, but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 colorectal cancer cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism rs992157 (2q35) and colorectal cancer was independently replicated (p=2.08x10(-4) ; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50x10(-9) ; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3, and 20q13.33 were associated with colorectal cancer in the Finnish population (false discovery rate <0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of colorectal cancer and identify shared risk alleles between the Finnish population isolate and outbred populations. This article is protected by copyright. All rights reserved. © 2017 UICC.

  3. A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations.

    PubMed

    Levin, Albert M; Mathias, Rasika A; Huang, Lili; Roth, Lindsey A; Daley, Denise; Myers, Rachel A; Himes, Blanca E; Romieu, Isabelle; Yang, Mao; Eng, Celeste; Park, Julie E; Zoratti, Karla; Gignoux, Christopher R; Torgerson, Dara G; Galanter, Joshua M; Huntsman, Scott; Nguyen, Elizabeth A; Becker, Allan B; Chan-Yeung, Moira; Kozyrskyj, Anita L; Kwok, Pui-Yan; Gilliland, Frank D; Gauderman, W James; Bleecker, Eugene R; Raby, Benjamin A; Meyers, Deborah A; London, Stephanie J; Martinez, Fernando D; Weiss, Scott T; Burchard, Esteban G; Nicolae, Dan L; Ober, Carole; Barnes, Kathleen C; Williams, L Keoki

    2013-04-01

    IgE is both a marker and mediator of allergic inflammation. Despite reported differences in serum total IgE levels by race-ethnicity, African American and Latino subjects have not been well represented in genetic studies of total IgE. We sought to identify the genetic predictors of serum total IgE levels. We used genome-wide association data from 4292 subjects (2469 African Americans, 1564 European Americans, and 259 Latinos) in the EVE Asthma Genetics Consortium. Tests for association were performed within each cohort by race-ethnic group (ie, African American, Latino, and European American) and asthma status. The resulting P values were meta-analyzed, accounting for sample size and direction of effect. Top single nucleotide polymorphism associations from the meta-analysis were reassessed in 6 additional cohorts comprising 5767 subjects. We identified 10 unique regions in which the combined association statistic was associated with total serum IgE levels (P<5.0×10(-6)) and the minor allele frequency was 5% or greater in 2 or more population groups. Variant rs9469220, corresponding to HLA-DQB1, was the single nucleotide polymorphism most significantly associated with serum total IgE levels when assessed in both the replication cohorts and the discovery and replication sets combined (P=.007 and 2.45×10(-7), respectively). In addition, findings from earlier genome-wide association studies were also validated in the current meta-analysis. This meta-analysis independently identified a variant near HLA-DQB1 as a predictor of total serum IgE levels in multiple race-ethnic groups. This study also extends and confirms the findings of earlier genome-wide association analyses in African American and Latino subjects. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  4. Factors associated with suicidal ideation in the general population: five-centre analysis from the ODIN study.

    PubMed

    Casey, Patricia R; Dunn, Graham; Kelly, Brendan D; Birkbeck, Gail; Dalgard, Odd Stefan; Lehtinen, Ville; Britta, Sohlam; Ayuso-Mateos, Jose Luis; Dowrick, Christopher

    2006-11-01

    Very few studies have examined the cross-national prevalence of suicidal ideation in the general population or variables associated with it. To examine the risk factors for suicidal ideas in the general population. As part of a five-country two stage epidemiological study of depressive disorder (the ODIN study) a random sample of over 12 000 people were screened using the Beck Depression Inventory (BDI). There followed detailed analysis of item 9 of the BDI, which measured the severity of suicidal ideation. Age, marriage, concern by others and severity of depressed mood independently increased or decreased the odds of suicidal ideation overall. An interaction between life events and social supports was identified, although this differed between men and women. Only concern by others and severity of depression were independently associated with serious suicidal ideation. The study does not allow for interpretation of the direction of the association. A number of social, clinical and demographic variables were independently associated with all suicidal ideation and with serious suicidal ideation. Longitudinal studies are required to confirm whether these are risk factors for or the result of suicidal ideation or have some other relationship.

  5. Association and meta-analysis of HLA and non-obstructive azoospermia in the Han Chinese population.

    PubMed

    Zou, S; Song, P; Meng, H; Chen, T; Chen, J; Wen, Z; Li, Z; Li, Z; Shi, Y; Hu, H

    2017-03-01

    The exact aetiology and pathogenesis of most non-obstructive azoospermia (NOA) are still unknown. The previous two genomewide association studies (GWASs) have identified three different loci within the HLA region for NOA in the Han Chinese population, including rs3129878, rs498422 and rs7194. To further validate the risk of three GWAS-linked loci for NOA, we conducted a case-control study of these three risk loci in an independent Han Chinese male population, with 603 NOA patients and 610 controls. Furthermore, we also performed a meta-analysis of five studies on these three NOA-risk loci. The case-control study strongly suggested a significant association between loci rs3129878, rs498422 and rs7194 and NOA (P = 6.75 × 10(-21) (OR = 2.2586), P = 0.0060 (OR = 1.4013) and P = 0.0128 (OR = 1.2626) respectively). Our meta-analyses also supported the susceptibility of these three risk loci to NOA (P < 0.01). The risk variants within the HLA region potentially have a strong effect on males at risk of NOA, and may serve as diagnostic markers for male infertility. However, considering genetic difference between different populations, future validating studies in larger independent samples and animal experiments are suggested.

  6. A population structure and genome-wide association analysis on the USDA soybean germplasm collection

    USDA-ARS?s Scientific Manuscript database

    Genotype-phenotype associations within the soybean (Glycine max) germplasm collection could provide valuable information on the frequency and distribution of alleles affecting economically important traits. Here we performed a genome-wide association study (GWAS) for seed protein and oil content in ...

  7. Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.

    PubMed

    Sabatti, Chiara; Service, Susan K; Hartikainen, Anna-Liisa; Pouta, Anneli; Ripatti, Samuli; Brodsky, Jae; Jones, Chris G; Zaitlen, Noah A; Varilo, Teppo; Kaakinen, Marika; Sovio, Ulla; Ruokonen, Aimo; Laitinen, Jaana; Jakkula, Eveliina; Coin, Lachlan; Hoggart, Clive; Collins, Andrew; Turunen, Hannu; Gabriel, Stacey; Elliot, Paul; McCarthy, Mark I; Daly, Mark J; Järvelin, Marjo-Riitta; Freimer, Nelson B; Peltonen, Leena

    2009-01-01

    Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.

  8. Genetic analysis of reelin gene (RELN) SNPs: no association with autism spectrum disorder in the Indian population.

    PubMed

    Dutta, Shruti; Sinha, Swagata; Ghosh, Saurabh; Chatterjee, Anindita; Ahmed, Shabina; Usha, Rajamma

    2008-08-15

    Involvement of reelin with Autism spectrum disorder (ASD) has been implicated through several biochemical as well as genetic studies. Reelin is an extracellular signaling protein, which plays a significant role in cytoarchitectonic pattern formation of different brain areas during development. Reelin gene (RELN) is located on chromosome 7q22; an important autism critical region identified through several genome-wide scans. A number of genetic studies have been carried out to investigate the association of reelin with autism. Recently we reported possible paternal effect in the transmission of CGG repeat alleles of RELN in the susceptibility towards autism. Further analysis on other polymorphisms is warranted to validate the status of RELN as a candidate for autism. Therefore in the present study, we have investigated six more SNPs (rs727531, rs2072403, rs2072402, rs362691, rs362719, rs736707) in 102 patients, 182 parents and 101 healthy controls. We have followed DSM-IV criteria and the screening for autism was carried out using CARS. Genomic DNA isolated from blood was used for PCR and subsequent RFLP analysis. Finally, case-control and family-based association studies were carried out to examine the genetic association of these SNP markers with ASD in the Indian population. But, we failed to detect either preferential parental transmission of any alleles of the markers to affected offspring or any biased allelic or genotypic distribution between the cases and controls. Thus the present study suggests that these SNPs of RELN are unlikely to be associated with ASD in the Indian population.

  9. A genome-wide association analysis for carcass traits in a commercial Duroc pig population.

    PubMed

    Eusebi, P G; González-Prendes, R; Quintanilla, R; Tibau, J; Cardoso, T F; Clop, A; Amills, M

    2017-08-01

    We performed a genome-wide association study to map the genetic determinants of carcass traits in 350 Duroc pigs typed with the Porcine SNP60 BeadChip. Association analyses were carried out using the gemma software. The proportion of phenotypic variance explained by the SNPs ranged between negligible to moderate (hSNP2= 0.01-0.30) depending on the trait under consideration. At the genome-wide level, we detected one significant association between backfat thickness between the 3(rd) and 4(th) ribs and six SNPs mapping to SSC12 (37-40 Mb). We also identified several chromosome-wide significant associations for ham weight (SSC11: 51-53 Mb, three SNPs; 67-68 Mb, two SNPs), carcass weight (SSC11: 66-68 Mb, two SNPs), backfat thickness between the 3(rd) and 4(th) ribs (SSC12: 21 Mb, one SNP; 33-40 Mb, 17 SNPs; 51-58 Mb, two SNPs), backfat thickness in the last rib (SSC12: 37 Mb, one SNP; 40-41 Mb, nine SNPs) and lean meat content (SSC13: 34 Mb, three SNPs and SSC16: 45.1 Mb, one SNP; 62-63 Mb, 10 SNPs; 71-75 Mb, nine SNPs). The ham weight trait-associated region on SSC11 contains two genes (UCHL3 and LMO7) related to muscle development. In addition, the ACACA gene, which encodes an enzyme for the catalysis of fatty acid synthesis, maps to the SSC12 (37-41 Mb) region harbouring trait-associated regions for backfat thickness traits. Sequencing of these candidate genes may help to uncover the causal mutations responsible for the associations found in the present study. © 2017 Stichting International Foundation for Animal Genetics.

  10. Association between PAI-1 4G/5G polymorphism and diabetic nephropathy: a meta-analysis in the Chinese population.

    PubMed

    Gao, Wen-Feng; Guo, Ying-Bo; Bai, Yu; Ding, Xin-Yu; Yan, Yong-Ji; Wu, Zhen-Qi

    2016-09-01

    Although a number of studies have been conducted on the association between plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and diabetic nephropathy (DN) in Chinese population, this association remains elusive and controversial. To further assess the effects of PAI-1 4G/5G polymorphism on the risk of DN, 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 November, 2015. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the associations. This meta-analysis identified nine studies, including 777 DN cases, 413 healthy controls, and 523 DM controls. In the total analyses, a significantly elevated risk of DN was associated with variants of PAI-1 4G/5G when compared with the healthy group (4G vs. 5G, OR 2.46, 95 % CI 1.45-4.16; 4G/4G vs. 5G/5G, OR 4.32, 95 % CI 1.79-10.39; 4G/4G vs. 4G/5G +5G/5G, OR 2.96, 95 % CI 1.59-5.53; 4G/4G +4G/5G vs. 5G/5G, OR 2.78, 95 % CI 1.34-5.75) and DM group (4G vs. 5G, OR 1.93, 95 % CI 1.28-2.92; 4G/4G vs. 5G/5G, OR 2.99, 95 % CI 1.44-6.21; 4G/4G vs. 4G/5G +5G/5G, OR 2.84, 95 % CI 1.77-4.54). In the subgroup analyses stratified by ethnicity and geographic areas, it revealed the significant results in Chinese Han, in North and South China. This meta-analysis showed that the PAI-1 4G/4G variant, 4G allele might be risk alleles for DN susceptibility in the Chinese population, and further studies in other ethic groups are required for definite conclusions.

  11. Genetic association analysis of 30 genes related to obesity in a European American population.

    PubMed

    Li, P; Tiwari, H K; Lin, W-Y; Allison, D B; Chung, W K; Leibel, R L; Yi, N; Liu, N

    2014-05-01

    Obesity, which is frequently associated with diabetes, hypertension and cardiovascular diseases, is primarily the result of a net excess of caloric intake over energy expenditure. Human obesity is highly heritable, but the specific genes mediating susceptibility in non-syndromic obesity remain unclear. We tested candidate genes in pathways related to food intake and energy expenditure for association with body mass index (BMI). We reanalyzed 355 common genetic variants of 30 candidate genes in seven molecular pathways related to obesity in 1982 unrelated European Americans from the New York Cancer Project. Data were analyzed by using a Bayesian hierarchical generalized linear model. The BMIs were log-transformed and then adjusted for covariates, including age, age(2), gender and diabetes status. The single-nucleotide polymorphisms (SNPs) were modeled as additive effects. With the stipulated adjustments, nine SNPs in eight genes were significantly associated with BMI: ghrelin (GHRL; rs35683), agouti-related peptide (AGRP; rs5030980), carboxypeptidase E (CPE; rs1946816 and rs4481204), glucagon-like peptide-1 receptor (GLP1R; rs2268641), serotonin receptors (HTR2A; rs912127), neuropeptide Y receptor (NPY5R;Y5R1c52), suppressor of cytokine signaling 3 (SOCS3; rs4969170) and signal transducer and activator of transcription 3 (STAT3; rs4796793). We also found a gender-by-SNP interaction (rs1745837 in HTR2A), which indicated that variants in the gene HTR2A had a stronger association with BMI in males. In addition, NPY1R was detected as having a significant gene effect even though none of the SNPs in this gene was significant. Variations in genes AGRP, CPE, GHRL, GLP1R, HTR2A, NPY1R, NPY5R, SOCS3 and STAT3 showed modest associations with BMI in European Americans. The pathways in which these genes participate regulate energy intake, and thus these associations are mechanistically plausible in this context.

  12. Association analysis revealed one susceptibility locus for vitiligo with immune-related diseases in the Chinese Han population.

    PubMed

    Li, Shu; Yao, Weiyi; Pan, Qian; Tang, Xianfa; Zhao, Suli; Wang, Wenjun; Zhu, Zhengwei; Gao, Jinping; Sheng, Yujun; Zhou, Fusheng; Zheng, Xiaodong; Zuo, Xianbo; Sun, Liangdan; Zhang, Anping

    2015-07-01

    Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other immune-related diseases. However, there is no reported study on the associations between immune susceptibility polymorphisms and the risk of vitiligo with immune-related diseases. The aim of this study was to evaluate the potential influence of 10 single-nucleotide polymorphisms (SNPs) at 18q21.31 (rs10503019), 4p16.1 (rs11940117), 3q28 (rs1464510), 14q12 (rs2273844), 12q13.2 (rs2456973), 16q12.2 (rs3213758), 10q25.3 (rs4353229), 3q13.33 (rs59374417), and 10p15.1 (rs706779 and rs7090530) on vitiligo with immune-related diseases in the Chinese Han population. All SNPs were genotyped in 552 patients with vitiligo-associated immune-related diseases and 1656 controls using the Sequenom MassArray system. Data were analyzed with PLINK 1.07 software. The C allele of rs2456973 at 12q13.2 was observed to be significantly associated with vitiligo-associated immune-related diseases (autoimmune diseases and allergic diseases) (P = 0.0028, odds ratio (OR) = 1.27). In subphenotype analysis, the rs2456973 C allele was also significantly associated with early-onset vitiligo by comparing with controls (P = 0.0001) and in the case-only analysis (P = 0.0114). We confirmed that 12q13.2 was an important candidate locus for vitiligo with immune-related diseases (autoimmune diseases and allergic diseases) and affected disease phenotypes with early onset.

  13. The association of Toxoplasma gondii infection with neurocognitive deficits in a population based analysis

    PubMed Central

    Pearce, Brad D.; Kruszon-Moran, Deanna; Jones, Jeffrey L.

    2014-01-01

    Purpose To examine the relationship between infection with Toxoplasma gondii (toxo) and cognition. Methods Multivariate logistic regression was used to test the association of toxo seropositivity with indices of cognitive function among over 4200 adults in the third National Health and Nutrition Examination Survey. Results Toxo-seropositive participants were more likely than seronegative participants to score in the worst quartile of the Simple Reaction Time Test (OR, 1.3, 95% CI 1.0,1.6), Symbol Digit Substitution Test (SDST, OR 1.5, 95% CI 1.2,1.9) and the Serial Digit Learning Test(trials to criterion) (SDLTNT, OR 1.4, 95% CI 1.1,1.8) in models adjusted for age, race/ethnicity, gender and foreign birth. After further adjustment for all cofactors, the association between toxo seropositivity and these outcomes was no longer significant. However, seropositivity was associated with worse scores on the SDST (OR 2.9, 95% CI 1.8,4.8) among those in the lowest income category and the SDLTNT (OR 1.5, 95% CI 1.1,2.5) among those foreign born. Conclusions Toxo seropositivity may be associated with poor cognitive test scores in certain subgroups, however, causation cannot be established in this cross sectional study. PMID:24477344

  14. Obstructive Sleep Apnea Susceptibility Genes in Chinese Population: A Field Synopsis and Meta-Analysis of Genetic Association Studies

    PubMed Central

    Tu, Chunlin; Zhong, Anyuan; Xu, Huajun

    2015-01-01

    Background Epidemiological studies to date have evaluated the association between genetic variants and the susceptibility to obstructive sleep apnea (OSA). However, the results of these studies have been inconclusive. In this current study we performed meta-analysis of genetic association studies (GAS) to pool OSA-susceptible genes in Chinese population, to perform a more precise evaluation of the association. Methods Various databases (i.e., PubMed, EMBASE, HuGE Navigator, Wanfang and CNKI) were searched to identify all eligible GAS-related variants associated with susceptibility to OSA. The generalized odds ratio metric (ORG) and the odds ratio (OR) of the allele contrast were used to quantify the impact of genetic variants on the risk of OSA. Cumulative and recursive cumulative meta-analyses (CMA) were also performed to investigate the trend and stability of effect sizes as evidence was accumulated. Results Thirty-two GAS evaluating 13 polymorphisms in 10 genes were included in our meta-analysis. Significant associations were derived for four polymorphisms either for the allele contrast or for the ORG. The variants TNF-α-308G/A, 5-HTTLPR, 5-HTTVNTR, and APOE showed marginal significance for ORG (95% confidence interval [CI]): 2.01(1.31–3.07); 1.31(1.09–1.58); 1.85(1.16–2.95); 1.79(1.10–2.92); and 1.79(1.10–2.92) respectively. In addition, the TNF-α-308G/A, 5-HTTLPR, and 5-HTTVNTR variants showed significance for the allele contrast: 2.15(1.39–3.31); 2.26(1.58–3.24); 1.32(1.12–1.55); and 1.86(1.12–3.08) respectively. CMA showed a trend towards an association, and recursive CMA indicated that more evidence was needed to determine whether this was significant. Conclusions TNF-α, 5-HTT, and APOE genes can all be proposed as OSA-susceptibility genes in Chinese population. Genome-wide association studies (GWAS) are therefore urgently needed to confirm our findings within a larger sample of OSA patients in China. PMID:26284518

  15. Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.

    PubMed

    Okada, Yukinori; Sim, Xueling; Go, Min Jin; Wu, Jer-Yuarn; Gu, Dongfeng; Takeuchi, Fumihiko; Takahashi, Atsushi; Maeda, Shiro; Tsunoda, Tatsuhiko; Chen, Peng; Lim, Su-Chi; Wong, Tien-Yin; Liu, Jianjun; Young, Terri L; Aung, Tin; Seielstad, Mark; Teo, Yik-Ying; Kim, Young Jin; Lee, Jong-Young; Han, Bok-Ghee; Kang, Daehee; Chen, Chien-Hsiun; Tsai, Fuu-Jen; Chang, Li-Ching; Fann, S-J Cathy; Mei, Hao; Rao, Dabeeru C; Hixson, James E; Chen, Shufeng; Katsuya, Tomohiro; Isono, Masato; Ogihara, Toshio; Chambers, John C; Zhang, Weihua; Kooner, Jaspal S; Albrecht, Eva; Yamamoto, Kazuhiko; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki; Kato, Norihiro; He, Jiang; Chen, Yuan-Tsong; Cho, Yoon Shin; Tai, E-Shyong; Tanaka, Toshihiro

    2012-07-15

    Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ∼110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.

  16. [Analysis of population survey for determining the factors associated with the control diabetes mellitus in Mexico].

    PubMed

    Hernández-Romieu, Alfonso Claudio; Elnecavé-Olaiz, Alejandro; Huerta-Uribe, Nidia; Reynoso-Noverón, Nancy

    2011-01-01

    Determine the influence of nutritional counseling, exercise, access to social healthcare and drugs, and the quality of medical care on the control of diabetics. The information and blood samples were obtained in 2005. Glycemic control was defined as good if HbA1c was ≤7.0%, poor from 7.01%-9.50% and very poor if HbA1c >9.5%. Binary logistic regression models were used to determine the association of these factors with HbA1c>9.5%. Thirty percent of the patients with a medical diagnosis of diabetes had adequate metabolic control. Nutritional guidance was associated with an increase in the degree of control. A majority of diabetics have poor or very poor glycemic control. Strengthening the quality of and access to medical care for these patients is urgently needed.

  17. Meta-Analysis of Rare Variant Association Tests in Multiethnic Populations.

    PubMed

    Mensah-Ablorh, Akweley; Lindstrom, Sara; Haiman, Christopher A; Henderson, Brian E; Marchand, Loic Le; Lee, Seunngeun; Stram, Daniel O; Eliassen, A Heather; Price, Alkes; Kraft, Peter

    2016-01-01

    Several methods have been proposed to increase power in rare variant association testing by aggregating information from individual rare variants (MAF < 0.005). However, how to best combine rare variants across multiple ethnicities and the relative performance of designs using different ethnic sampling fractions remains unknown. In this study, we compare the performance of several statistical approaches for assessing rare variant associations across multiple ethnicities. We also explore how different ethnic sampling fractions perform, including single-ethnicity studies and studies that sample up to four ethnicities. We conducted simulations based on targeted sequencing data from 4,611 women in four ethnicities (African, European, Japanese American, and Latina). As with single-ethnicity studies, burden tests had greater power when all causal rare variants were deleterious, and variance component-based tests had greater power when some causal rare variants were deleterious and some were protective. Multiethnic studies had greater power than single-ethnicity studies at many loci, with inclusion of African Americans providing the largest impact. On average, studies including African Americans had as much as 20% greater power than equivalently sized studies without African Americans. This suggests that association studies between rare variants and complex disease should consider including subjects from multiple ethnicities, with preference given to genetically diverse groups.

  18. Dermal digital ridge density of a penal population: Analysis of association and individualization.

    PubMed

    Kaur, Maninder; Sharma, Krishan

    2016-11-01

    The present study is an attempt to analyze an association between dermal digital ridge density and explosive personality based on the study of 100 male prisoners and 50 controls. The control group had higher ridge density than the prisoners. Bilateral differences revealed higher ridge density on left hand than right hand in both the groups, but differences between two groups for directional asymmetry were not significant. Surface area is not correlated with ridge density in all the digits. About 50% of the variation in ridge density may be explained by a single factor which in all probability is the genetic component of variation. Ridge density cannot be used as a marker for assessing individual's height. Individuals having ridge density less than 12 ridges and higher than 15 ridges, i.e. placed on the two extremes were more likely than not to have more explosive personality. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  19. Association of mild to moderate chronic kidney disease with venous thromboembolism: pooled analysis of five prospective general population cohorts.

    PubMed

    Mahmoodi, Bakhtawar K; Gansevoort, Ron T; Næss, Inger Anne; Lutsey, Pamela L; Brækkan, Sigrid K; Veeger, Nic J G M; Brodin, Ellen E; Meijer, Karina; Sang, Yingying; Matsushita, Kunihiro; Hallan, Stein I; Hammerstrøm, Jens; Cannegieter, Suzanne C; Astor, Brad C; Coresh, Josef; Folsom, Aaron R; Hansen, John-Bjarne; Cushman, Mary

    2012-10-16

    Recent findings suggest that chronic kidney disease (CKD) may be associated with an increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted. We pooled individual participant data from 5 community-based cohorts from Europe (second Nord-Trøndelag Health Study [HUNT2], Prevention of Renal and Vascular End-stage Disease [PREVEND], and the Tromsø study) and the United States (Atherosclerosis Risks in Communities [ARIC] and Cardiovascular Health Study [CHS]) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria, and CKD with objectively verified VTE. To estimate adjusted hazard ratios for VTE, categorical and continuous spline models were fit by using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1178 VTE events occurred over 599 453 person-years follow-up. Relative to eGFR 100 mL/min per 1.73 m(2), hazard ratios for VTE were 1.29 (95% confidence interval, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for eGFR 60, 1.82 (1.27-2.60) for eGFR 45, and 1.95 (1.26-3.01) for eGFR 30 mL/min per 1.73 m(2). In comparison with an albumin-to-creatinine ratio (ACR) of 5.0 mg/g, the hazard ratios for VTE were 1.34 (1.04-1.72) for ACR 30 mg/g, 1.60 (1.08-2.36) for ACR 300 mg/g, and 1.92 (1.19-3.09) for ACR 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted hazard ratio for CKD, defined as eGFR <60 mL/min per 1.73 m(2) or albuminuria ≥30 mg/g, (versus no CKD) was 1.54 (95% confidence interval, 1.15-2.06). Associations were consistent in subgroups according to age, sex, and comorbidities, and for unprovoked versus provoked VTE, as well. Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges.

  20. Association of Mild to Moderate Chronic Kidney Disease with Venous Thromboembolism: Pooled Analysis of Five Prospective General Population Cohorts

    PubMed Central

    Mahmoodi, Bakhtawar K.; Gansevoort, Ron T.; Næss, Inger Anne; Lutsey, Pamela L.; Brækkan, Sigrid K.; Veeger, Nic J. G. M.; Brodin, Ellen E.; Meijer, Karina; Sang, Yingying; Matsushita, Kunihiro; Hallan, Stein I.; Hammerstrøm, Jens; Cannegieter, Suzanne C.; Astor, Brad C.; Coresh, Josef; Folsom, Aaron R.; Hansen, John-Bjarne; Cushman, Mary

    2012-01-01

    Background Recent findings suggest that chronic kidney disease (CKD) may be associated with increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted. Methods and Results We pooled individual participant data from five community-based cohorts from Europe (HUNT2, PREVEND and Tromsø study) and United States (ARIC and CHS study) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria and CKD with objectively verified VTE. To estimate adjusted hazard ratios (HRs) for VTE, categorical and continuous spline models were fit using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1,178 VTE events occurred over 599,453 person-years follow-up. Relative to eGFR 100 mL/min/1.73m2, HRs for VTE were 1.29 (95%CI, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for 60, 1.82 (1.27-2.60) for 45 and 1.95 (1.26-3.01) for 30 mL/min/1.73m2. Compared with albumin-creatinine ratio (ACR) of 5.0 mg/g, the HRs for VTE were 1.34 (1.04-1.72) for 30 mg/g, 1.60 (1.08-2.36) for 300 mg/g and 1.92 (1.19-3.09) for 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted HR for CKD defined as eGFR <60 mL/min/1.73m2 or albuminuria ≥30 mg/g (vs. no CKD) was 1.54 (95%CI, 1.15-2.06). Associations were consistent in subgroups according to age, gender, and comorbidities as well as for unprovoked versus provoked VTE. Conclusions Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges. PMID:22977129

  1. Molecular analysis and conventional cytology: association between HPV and bacterial vaginosis in the cervical abnormalities of a Brazilian population.

    PubMed

    Peres, A L; Camarotti, J R S L; Cartaxo, M; Alencar, N; Stocco, R C; Beçak, W; Pontes-Filho, N T; Araújo, R F F; Lima-Filho, J L; Martins, D B G

    2015-08-14

    We investigated the association between bacterial vaginosis (BV) and human papillomavirus (HPV) infection in Papanicolaou smears in a Brazilian population. Cross-sectional analysis was performed on 673 samples collected from women attending public health centers in Olinda (PE, Brazil) by conventional cytology methodology and molecular analysis, PCR tests (GP5+/6+ and MY09/11). Cytological abnormalities, BV, and HPV-DNA were detected in 23 (3.4%) samples, 189 samples (28.1%), and 210 samples (31.2%), respectively. GP5+/6+ primers resulted in higher detection performance than MY09/11 primers, with 81% concordance between both primers (P < 0.0001). The occurrence of HPV-DNA and BV had ORs of 8.59 (P < 0.0001) and 2.91 (P = 0.0089) for abnormal cytology, respectively, whereas the concomitant presence of both infections showed an OR equal to 3.82 (P = 0.0054). Therefore, we observed an association between abnormal cervical cytology and HPV infection, BV, or both HPV infection and BV. These results highlight the necessity of monitoring patients presenting not only HPV, but also BV, as risk factors for cervical lesion development.

  2. Joint-multiple family linkage analysis predicts within-family variation better than single-family analysis of the maize nested association mapping population.

    PubMed

    Ogut, F; Bian, Y; Bradbury, P J; Holland, J B

    2015-06-01

    Quantitative trait locus (QTL) mapping has been used to dissect the genetic architecture of complex traits and predict phenotypes for marker-assisted selection. Many QTL mapping studies in plants have been limited to one biparental family population. Joint analysis of multiple biparental families offers an alternative approach to QTL mapping with a wider scope of inference. Joint-multiple population analysis should have higher power to detect QTL shared among multiple families, but may have lower power to detect rare QTL. We compared prediction ability of single-family and joint-family QTL analysis methods with fivefold cross-validation for 6 diverse traits using the maize nested association mapping population, which comprises 25 biparental recombinant inbred families. Joint-family QTL analysis had higher mean prediction abilities than single-family QTL analysis for all traits at most significance thresholds, and was always better at more stringent significance thresholds. Most robust QTL (detected in >50% of data samples) were restricted to one family and were often not detected at high frequency by joint-family analysis, implying substantial genetic heterogeneity among families for complex traits in maize. The superior predictive ability of joint-family QTL models despite important genetic differences among families suggests that joint-family models capture sufficient smaller effect QTL that are shared across families to compensate for missing some rare large-effect QTL.

  3. Association of workplace and population characteristics with prevalence of hypertension among Brazilian industry workers: a multilevel analysis.

    PubMed

    Vinholes, Daniele B; Bassanesi, Sérgio L; Chaves Junior, Hilton de Castro; Machado, Carlos Alberto; Melo, Ione M F; Fuchs, Flavio Danni; Fuchs, Sandra Costa

    2017-08-21

    Exposure to risk factors for hypertension may be influenced by the characteristics of the workplace, where workers spend most of their daily time. To evaluate the association between features of the companies, particularly the presence of facilities to provide meals, and of population characteristics and the prevalence of hypertension, taking into account individual risk factors for hypertension. This multilevel analysis was based on a cross-sectional study with individual and company data from the SESI (Serviço Social da Indústria-Social Service of Industries) study and population-based data from the national census statistics. Workers aged ≥15 years were randomly selected from small (20-99), medium (100-499) and large (≥500 employees) companies per state using multistage sampling. Logistic regression was used to analyse the association between hypertension and individual, workplace and population variables, with odds ratios (ORs; 95% CI) adjusted for three-level variables. 4818 Workers from 157 companies were interviewed and their blood pressure, weight and height were measured. Overall, 77% were men, aged 35.4 ±10.7 years, with 8.7 ±4.1 years of schooling and mostly worked in companies with a staff canteen (66%). Besides individual characteristics-being male, ageing, low schooling, alcohol abuse and higher BMI-a workplace with no staff canteen (OR=1.28; 95% CI 1.08 to 1.52), small companies (OR=1.31; 95% CI 1.07 to 1.60) and living in cities with higher economic inequality (OR=1.47; 95% CI 1.23 to 1.76) were associated with a higher risk for hypertension. Among Brazilian workers, the prevalence of hypertension is associated with individual risk factors, lack of a canteen at the workplace, small companies and higher economic inequalities of cities. These three-level characteristics help to interpret differences in the prevalence of hypertension between regions or countries. © Article author(s) (or their employer(s) unless otherwise stated in the

  4. Genetic Structure and Relationship Analysis of an Association Population in Jute (Corchorus spp.) Evaluated by SSR Markers.

    PubMed

    Zhang, Liwu; Yuan, Minhang; Tao, Aifen; Xu, Jiantang; Lin, Lihui; Fang, Pingping; Qi, Jianmin

    2015-01-01

    Population structure and relationship analysis is of great importance in the germplasm utilization and association mapping. Jute, comprised of white jute (C. capsularis L) and dark jute (C. olitorius L), is second to cotton in its commercial significance in the world. Here, we assessed the genetic structure and relationship in a panel of 159 jute accessions from 11 countries and regions using 63 SSRs. The structure analysis divided the 159 jute accessions from white and dark jute into Co and Cc group, further into Co1, Co2, Cc1 and Cc2 subgroups. Out of Cc1 subgroup, 81 accessions were from China and the remaining 10 accessions were from India (2), Japan (5), Thailand, Vietnam (2) and Pakistan (1). Out of Cc2 subgroup, 35 accessions were from China, and the remaining 3 accessions were from India, Pakistan and Thailand respectively. It can be inferred that the genetic background of these jute accessions was not always correlative with their geographical regions. Similar results were found in Co1 and Co2 subgroups. Analysis of molecular variance revealed 81% molecular variation between groups but it was low (19%) within subgroups, which further confirmed the genetic differentiation between the two groups. The genetic relationship analysis showed that the most diverse genotypes were Maliyeshengchangguo and Changguozhongyueyin in dark jute, BZ-2-2, Aidianyehuangma, Yangjuchiyuanguo, Zijinhuangma and Jute 179 in white jute, which could be used as the potential parents in breeding programs for jute improvement. These results would be very useful for association studies and breeding in jute.

  5. The Relation Between Inflation in Type-I and Type-II Error Rate and Population Divergence in Genome-Wide Association Analysis of Multi-Ethnic Populations.

    PubMed

    Derks, E M; Zwinderman, A H; Gamazon, E R

    2017-02-10

    Population divergence impacts the degree of population stratification in Genome Wide Association Studies. We aim to: (i) investigate type-I error rate as a function of population divergence (FST) in multi-ethnic (admixed) populations; (ii) evaluate the statistical power and effect size estimates; and (iii) investigate the impact of population stratification on the results of gene-based analyses. Quantitative phenotypes were simulated. Type-I error rate was investigated for Single Nucleotide Polymorphisms (SNPs) with varying levels of FST between the ancestral European and African populations. Type-II error rate was investigated for a SNP characterized by a high value of FST. In all tests, genomic MDS components were included to correct for population stratification. Type-I and type-II error rate was adequately controlled in a population that included two distinct ethnic populations but not in admixed samples. Statistical power was reduced in the admixed samples. Gene-based tests showed no residual inflation in type-I error rate.

  6. Associations between the Genetic Polymorphisms of Osteopontin Promoter and Susceptibility to Cancer in Chinese Population: A Meta-Analysis.

    PubMed

    Liu, Yulan; Lei, Hongbo; Zhang, Jixiang; Wang, Jun; Li, Kui; Dong, Weiguo

    2015-01-01

    Several studies have been conducted to examine the associations between osteopontin (OPN) promoter gene SPP1 polymorphisms with human cancers in Chinese population, but the results remain inconsistent. The aim of this meta-analysis is to clarify the associations between SPP1 polymorphisms and cancer susceptibility. All eligible case-control studies published up to March 2015 were identified by searching PubMed, Web of Science, Embase, and Cochrane Library without language restrictions. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated using fixed- or random-effect model. A total of 11 case-control studies were included; of those, there were eleven studies (3130 cases and 3828 controls) for -443T>C polymorphism, ten studies (3019 cases and 3615 controls) for -156G>GG polymorphism, eight studies (2258 cases and 2846 controls) for -66T>G polymorphism. Overall, no evidence indicated that the -443 T>C polymorphism was associated with cancer risk (OR = 0.93, 95%CI 0.62-1.38 for dominant model, OR = 1.06, 95%CI 0.73-1.55 for recessive model, OR = 0.88, 95%CI 0.62-1.26 for CT vs TT model, OR = 1.03, 95%CI 0.61-1.73 for CC vs TT model). While, a significantly increase risk was found for -156 G>GG polymorphism (OR = 1.22, 95%CI 1.10-1.35 for dominant model, OR = 1.25, 95%CI 1.10-1.41 for recessive model, OR = 1.18, 95%CI 1.06-1.32 for GGG vs GG model, OR = 1.35, 95%CI 1.09-1.68 for GGGG vs GG model). For -66T>G polymorphism, we found a decrease risk of cancer (OR = 0.84, 95% CI 0.71-0.98 for dominant model), but this result changed (OR = 0.93, 95% CI 0.77-1.12 for dominant model) when we excluded a study. This meta-analysis suggests that in Chinese population the -156G>GG polymorphism of SPP1 might be a risk factor for human cancers, while -443T>C mutation is not associated with cancer risk. For -66T>G polymorphism, it may be a protective factor for human cancers.

  7. Associations between the Genetic Polymorphisms of Osteopontin Promoter and Susceptibility to Cancer in Chinese Population: A Meta-Analysis

    PubMed Central

    Zhang, Jixiang; Wang, Jun; Li, Kui; Dong, Weiguo

    2015-01-01

    Background and Aim Several studies have been conducted to examine the associations between osteopontin (OPN) promoter gene SPP1 polymorphisms with human cancers in Chinese population, but the results remain inconsistent. The aim of this meta-analysis is to clarify the associations between SPP1 polymorphisms and cancer susceptibility. Methods All eligible case-control studies published up to March 2015 were identified by searching PubMed, Web of Science, Embase, and Cochrane Library without language restrictions. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated using fixed- or random-effect model. Results A total of 11 case-control studies were included; of those, there were eleven studies (3130 cases and 3828 controls) for -443T>C polymorphism, ten studies (3019 cases and 3615 controls) for -156G>GG polymorphism, eight studies (2258 cases and 2846 controls) for -66T>G polymorphism. Overall, no evidence indicated that the -443 T>C polymorphism was associated with cancer risk (OR = 0.93, 95%CI 0.62–1.38 for dominant model, OR = 1.06, 95%CI 0.73–1.55 for recessive model, OR = 0.88, 95%CI 0.62–1.26 for CT vs TT model, OR = 1.03, 95%CI 0.61–1.73 for CC vs TT model). While, a significantly increase risk was found for -156 G>GG polymorphism (OR = 1.22, 95%CI 1.10–1.35 for dominant model, OR = 1.25, 95%CI 1.10–1.41 for recessive model, OR = 1.18, 95%CI 1.06–1.32 for GGG vs GG model, OR = 1.35, 95%CI 1.09–1.68 for GGGG vs GG model). For -66T>G polymorphism, we found a decrease risk of cancer (OR = 0.84, 95% CI 0.71–0.98 for dominant model), but this result changed (OR = 0.93, 95% CI 0.77–1.12 for dominant model) when we excluded a study. Conclusion This meta-analysis suggests that in Chinese population the -156G>GG polymorphism of SPP1 might be a risk factor for human cancers, while -443T>C mutation is not associated with cancer risk. For -66T>G polymorphism, it may be a protective factor for human cancers. PMID:26267616

  8. The association and interaction analysis of hypertension and diabetes mellitus on diastolic heart failure in a high-risk population

    PubMed Central

    Meng, Xiang-Ying; Zhou, Yong; Zhang, Jin; Tang, Zi-Hui

    2015-01-01

    Objective: The purpose of this study was to evaluate the extent to which hypertension (HT) interacts with diabetes mellitus (DM) to affect diastolic heart failure (DHF) in a high-risk population. Methods: We conducted a hospital-based case-control study to investigate the relationship between HT or DM and DHF in 251 patients (case: 133 patients with DHF; control: 118 patients without DHF). Echocardiography was used to assess left ventricular (LV) diastolic function. The association between HT or DM and DHF was assessed by multivariate logistic regression (MLR) analysis controlling for confounders. The effect of the interaction between HT and DM on DHF was assessed in MLR models. Interaction on an additive scale can be calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). Results: The MLR analyses showed that HT and DM were independent predictors of DHF after adjustment for potential confounders (OR = 2.35-3.14, P<0.05 for all models). DHF was affected by the interaction between HT and DM (ORInt = 3.11-4.31, P Int<0.1, RETI = 2.13-2.69, AP = 0.38-0.49 and S = 4.11-6.80). Conclusion: The findings provide evidence that HT and DM are independent predictors of DHF and that both risk factors act synergistically to influence DHF in a Chinese high-risk population. PMID:26885071

  9. The association and interaction analysis of hypertension and diabetes mellitus on diastolic heart failure in a high-risk population.

    PubMed

    Meng, Xiang-Ying; Zhou, Yong; Zhang, Jin; Tang, Zi-Hui

    2015-01-01

    The purpose of this study was to evaluate the extent to which hypertension (HT) interacts with diabetes mellitus (DM) to affect diastolic heart failure (DHF) in a high-risk population. We conducted a hospital-based case-control study to investigate the relationship between HT or DM and DHF in 251 patients (case: 133 patients with DHF; control: 118 patients without DHF). Echocardiography was used to assess left ventricular (LV) diastolic function. The association between HT or DM and DHF was assessed by multivariate logistic regression (MLR) analysis controlling for confounders. The effect of the interaction between HT and DM on DHF was assessed in MLR models. Interaction on an additive scale can be calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). The MLR analyses showed that HT and DM were independent predictors of DHF after adjustment for potential confounders (OR = 2.35-3.14, P<0.05 for all models). DHF was affected by the interaction between HT and DM (ORInt = 3.11-4.31, P Int<0.1, RETI = 2.13-2.69, AP = 0.38-0.49 and S = 4.11-6.80). The findings provide evidence that HT and DM are independent predictors of DHF and that both risk factors act synergistically to influence DHF in a Chinese high-risk population.

  10. Association of regional and cultural factors with the prevalence of rheumatoid arthritis in the Mexican population: a multilevel analysis.

    PubMed

    Moreno-Montoya, José; Alvarez-Nemegyei, José; Sanin, Luz Helena; Pérez-Barbosa, Lorena; Trejo-Valdivia, Belem; Santana, Natalia; Goycochea-Robles, Maria Victoria; Cardiel, Mario Humberto; Riega-Torres, Janeth; Maradiaga, Marco; Burgos-Vargas, Rubén; Peláez-Ballestas, Ingris

    2015-03-01

    The overall estimated prevalence of rheumatoid arthritis (RA) in Mexico is 1.6%, but there are major variations in different geographic areas of the country. This study aimed to determine the impact of individual and regional variables on the geographic distribution of RA in Mexico. This multilevel analysis used data from a cross-sectional study that investigated the prevalence of RA among 19,213 individuals older than 18 years throughout 5 geographic regions in Mexico. Logistic regression models were used to determine predictors of RA, including individual and regional variables as well as cultural factors. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were determined. The prevalence of RA varied from 0.77% to 2.8% across the 5 regions. Individual factors associated with RA were sex (OR, 2.32; 95% CI, 1.74-3.07), previous medical diagnosis of RA ( OR 3.3, 95%CI: 2919–5.1 [corrected]), disability (OR, 2.07; 95% CI, 1.48-2.93), and the 56- to 65-year age group (OR, 1.95; 95% CI, 1.08-3.74). The regional factor of speaking an indigenous language had an OR of 2.27 (95% CI, 1.13-4.55). Various individual and regional factors were associated with variations in the prevalence of RA in the Mexican population.

  11. Genome Wide Association Analysis of a Founder Population Identified TAF3 as a Gene for MCHC in Humans

    PubMed Central

    Pistis, Giorgio; Okonkwo, Shawntel U.; Traglia, Michela; Sala, Cinzia; Shin, So-Youn; Masciullo, Corrado; Buetti, Iwan; Massacane, Roberto; Mangino, Massimo; Thein, Swee-Lay; Spector, Timothy D.; Ganesh, Santhi; Pirastu, Nicola; Gasparini, Paolo; Soranzo, Nicole; Camaschella, Clara; Hart, Daniel; Green, Michael R.; Toniolo, Daniela

    2013-01-01

    The red blood cell related traits are highly heritable but their genetics are poorly defined. Only 5–10% of the total observed variance is explained by the genetic loci found to date, suggesting that additional loci should be searched using approaches alternative to large meta analysis. GWAS (Genome Wide Association Study) for red blood cell traits in a founder population cohort from Northern Italy identified a new locus for mean corpuscular hemoglobin concentration (MCHC) in the TAF3 gene. The association was replicated in two cohorts (rs1887582, P = 4.25E–09). TAF3 encodes a transcription cofactor that participates in core promoter recognition complex, and is involved in zebrafish and mouse erythropoiesis. We show here that TAF3 is required for transcription of the SPTA1 gene, encoding alpha spectrin, one of the proteins that link the plasma membrane to the actin cytoskeleton. Mutations in SPTA1 are responsible for hereditary spherocytosis, a monogenic disorder of MCHC, as well as for the normal MCHC level. Based on our results, we propose that TAF3 is required for normal erythropoiesis in human and that it might have a role in controlling the ratio between hemoglobin (Hb) and cell volume and in the dynamics of RBC maturation in healthy individuals. Finally, TAF3 represents a potential candidate or a modifier gene for disorders of red cell membrane. PMID:23935956

  12. Analysis of Genomic Regions Associated With Coronary Artery Disease Reveals Continent-Specific Single Nucleotide Polymorphisms in North African Populations.

    PubMed

    Zanetti, Daniela; Via, Marc; Carreras-Torres, Robert; Esteban, Esther; Chaabani, Hassen; Anaibar, Fatima; Harich, Nourdin; Habbal, Rachida; Ghalim, Noreddine; Moral, Pedro

    2016-05-05

    In recent years, several genomic regions have been robustly associated with coronary artery disease (CAD) in different genome-wide association studies (GWASs) conducted mainly in people of European descent. These kinds of data are lacking in African populations, even though heart diseases are a major cause of premature death and disability. Here, 384 single nucleotide polymorphisms (SNPs) in the top four CAD risk regions (1p13, 1q41, 9p21, and 10q11) were genotyped in 274 case-control samples from Morocco and Tunisia, with the aim of analyzing for the first time if the associations found in European populations were transferable to North Africans. The results indicate that, as in Europe, these four genetic regions are also important for CAD risk in North Africa. However, the individual SNPs associated with CAD in Africa are different from those identified in Europe in most cases (1p13, 1q41, and 9p21). Moreover, the seven risk variants identified in North Africans are efficient in discriminating between cases and controls in North African populations, but not in European populations. This study indicates a disparity in markers associated to CAD susceptibility between North Africans and Europeans that may be related to population differences in the chromosomal architecture of these risk regions.

  13. Genome-wide association analysis on five isolated populations identifies variants of the HLA-DOA gene associated with white wine liking

    PubMed Central

    Pirastu, Nicola; Kooyman, Maarten; Traglia, Michela; Robino, Antonietta; Willems, Sara M; Pistis, Giorgio; Amin, Najaf; Sala, Cinzia; Karssen, Lennart C; van Duijn, Cornelia M; Toniolo, Daniela; Gasparini, Paolo

    2015-01-01

    Wine is the most popular alcoholic beverage around the world and because of its importance in society has been widely studied. Understanding what drives its flavor has been a quest for decades but much is still unknown and will be determined at least in part by individual taste preferences. Recently studies in the genetics of taste have uncovered the role of different genes in the determination of food preferences giving new insight on its physiology. In this context we have performed a genome-wide association study on red and white wine liking using three isolated populations collected in Italy, and replicated our results on two additional populations coming from the Netherland and Central Asia for a total of 3885 samples. We have found a significant association (P=2.1 × 10−8) between white wine liking and rs9276975:C>T a polymorphism in the HLA-DOA gene encoding a non-canonical MHC II molecule, which regulates other MHC II molecules. The same association was also found with red wine liking (P=8.3 × 10−6). Sex-separated analysis have also revealed that the effect of HLA-DOA is twice as large in women as compared to men suggesting an interaction between this polymorphism and gender. Our results are one of the first examples of genome-wide association between liking of a commonly consumed food and gene variants. Moreover, our results suggest a role of the MHC system in the determination of food preferences opening new insight in this field in general. PMID:25758996

  14. Genome-wide association analysis on five isolated populations identifies variants of the HLA-DOA gene associated with white wine liking.

    PubMed

    Pirastu, Nicola; Kooyman, Maarten; Traglia, Michela; Robino, Antonietta; Willems, Sara M; Pistis, Giorgio; Amin, Najaf; Sala, Cinzia; Karssen, Lennart C; van Duijn, Cornelia M; Toniolo, Daniela; Gasparini, Paolo

    2015-12-01

    Wine is the most popular alcoholic beverage around the world and because of its importance in society has been widely studied. Understanding what drives its flavor has been a quest for decades but much is still unknown and will be determined at least in part by individual taste preferences. Recently studies in the genetics of taste have uncovered the role of different genes in the determination of food preferences giving new insight on its physiology. In this context we have performed a genome-wide association study on red and white wine liking using three isolated populations collected in Italy, and replicated our results on two additional populations coming from the Netherland and Central Asia for a total of 3885 samples. We have found a significant association (P=2.1 × 10(-8)) between white wine liking and rs9276975:C>T a polymorphism in the HLA-DOA gene encoding a non-canonical MHC II molecule, which regulates other MHC II molecules. The same association was also found with red wine liking (P=8.3 × 10(-6)). Sex-separated analysis have also revealed that the effect of HLA-DOA is twice as large in women as compared to men suggesting an interaction between this polymorphism and gender. Our results are one of the first examples of genome-wide association between liking of a commonly consumed food and gene variants. Moreover, our results suggest a role of the MHC system in the determination of food preferences opening new insight in this field in general.

  15. Linkage disequilibrium and association analysis of alpha-synuclein and alcohol and drug dependence in two American Indian populations.

    PubMed

    Clarimon, Jordi; Gray, Rebecca R; Williams, Lindsey N; Enoch, Mary-Anne; Robin, Robert W; Albaugh, Bernard; Singleton, Andrew; Goldman, David; Mulligan, Connie J

    2007-04-01

    Alpha-synuclein is involved in dopaminergic neurotransmission and has been implicated in a number of neurodegenerative disorders, such as Parkinson's disease. Recent studies, in humans and in rat and monkey models, have suggested that alpha-synuclein may play a role in the development and maintenance of certain addictive disorders. Fifteen single-nucleotide polymorphisms (SNPs) in the alpha-synuclein gene (SNCA) and 1 upstream microsatellite repeat (NACP-REP1) were assayed in Southwest (SW; n=514) and Plains (n=420) American Indian populations. Patterns of linkage disequilibrium (LD) at SNCA were determined for the 2 populations and compared with Caucasian, African, and Asian populations in the HapMap database (http://www.hapmap.org). Assayed alleles and constructed haplotypes in the study populations were tested for association with 4 clinical phenotypes [alcohol dependence, alcohol use disorders, drug dependence, and drug use disorders (lifetime diagnoses)] as well as with 2 symptom count phenotypes (all 18 questions and the 8 questions diagnostic for alcohol dependence). Patterns of LD at SNCA were similar in both Indian populations and were consistent with the LD structure in other populations as reflected in the HapMap database. Single allele tests revealed significant associations between 4 SNPs and drug dependence in the SW population and between 2 of those SNPs plus 2 other SNPs and drug dependence in SW males only. In the Plains population, a significant association was detected only in males between 2 SNPs and alcohol use disorders and between 1 SNP and alcohol dependence. In the SW population, 1 SNP was marginally significant with the total symptom count. However, in all cases, the support was modest and disappeared with correction for multiple comparisons. No association was found between constructed haplotypes and any of the phenotypes in either population. Despite modest support for association between multiple SNCA SNPs and several of the addictive

  16. [Variables associated with the use of dental services among preschool population in Spain: a national health survey analysis].

    PubMed

    Barriuso Lapresa, Laura; Sanz-Barbero, Belén

    2012-01-01

    oral health is integral to health from the eruption of the first tooth. To achieving, it is necessary an early establishment of healthy oral habits as regular dental checkups. In developed countries, caries is the most prevalent chronic pediatric disease and it may be increasing in preschool age. a) assessing prevalence of oral health services use among Spanish preschool population, b) quantifying and analyzing the existence of variability among autonomous community and c) identifying variables associated with such use. cross-sectional study about Spanish National health Survey (2006). 2,172 children aged between 2 and 5 years (both inclusive). have gone to dental services at least once during life. sociodemographic, self-referred dental health, habits and family socioeconomic status variables. Multivariate logistic regression analysis. 20.8% of Spanish preschoolers reported had attended dental services. Probability of use increased with age (OR: 1,88; IC:1,53-2,31), frequency of daily tooth brushing (three or more times per day vrs less than once: OR: 2,94; IC: 1,47-5,87) and presence of caries (OR: 2,60; IC: 1,22-5,51). There is a socioeconomic gradient about probability of use: it increased with family socioeconomic status measured by social class (low vrs high: OR: 0,41; IC: 0,19-0,86) and maternal educational level (OR: 1,62; IC: 1,13-2,32). There was not variability in the oral health services use attributable to the autonomous community. the use of dental health services among Spanish preschool population is lower than desirable. The promotion of its use should be intensified in children from disadvantaged families.

  17. Meta-analysis of the association between SNPs in TCF7L2 and type 2 diabetes in East Asian population.

    PubMed

    Luo, Yingying; Wang, Hongyuan; Han, Xueyao; Ren, Qian; Wang, Fang; Zhang, Xiuying; Sun, Xiuqin; Zhou, Xianghai; Ji, Linong

    2009-08-01

    To evaluate the effect of TCF7L2 on genetic susceptibility of type 2 diabetes (T2DM) in East Asian population by using the meta-analysis. Search all the publications about the association between TCF7L2 and T2DM in East Asian population from PubMed, CNKI and abstracts of major diabetes conferences. Perform the meta-analysis of all the validated studies and evaluate the association between rs7903146 T allele, rs12255372 T allele, rs11196205 C allele, rs290487 C allele and rs11196218 G allele of TCF7L2 and the risk of T2DM. Eleven studies from nine eligible papers and one unpublished study of ours were included in the meta-analysis. Ten eligible studies were analyzed for rs7903146, five were analyzed for rs12255372 and rs11196205, and three were analyzed for rs290487 and rs11196218. We found that four SNPs (rs7903146, rs12255372, rs11196205, rs290487) in TCF7L2 were significantly associated with T2DM in East Asian populations. The rs11196218 also showed a marginal association. The estimated population-attributable risk (PAR) associated with analyzed SNPs ranged from 2% to 7%. SNPs in TCF7L2 were strongly associated with the risk of T2DM in East Asian population. But the contribution of its genetic variants to the epidemic of type 2 diabetes in East Asian was relatively low.

  18. Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.

    PubMed

    Franceschini, Nora; Fox, Ervin; Zhang, Zhaogong; Edwards, Todd L; Nalls, Michael A; Sung, Yun Ju; Tayo, Bamidele O; Sun, Yan V; Gottesman, Omri; Adeyemo, Adebawole; Johnson, Andrew D; Young, J Hunter; Rice, Ken; Duan, Qing; Chen, Fang; Li, Yun; Tang, Hua; Fornage, Myriam; Keene, Keith L; Andrews, Jeanette S; Smith, Jennifer A; Faul, Jessica D; Guangfa, Zhang; Guo, Wei; Liu, Yu; Murray, Sarah S; Musani, Solomon K; Srinivasan, Sathanur; Velez Edwards, Digna R; Wang, Heming; Becker, Lewis C; Bovet, Pascal; Bochud, Murielle; Broeckel, Ulrich; Burnier, Michel; Carty, Cara; Chasman, Daniel I; Ehret, Georg; Chen, Wei-Min; Chen, Guanjie; Chen, Wei; Ding, Jingzhong; Dreisbach, Albert W; Evans, Michele K; Guo, Xiuqing; Garcia, Melissa E; Jensen, Rich; Keller, Margaux F; Lettre, Guillaume; Lotay, Vaneet; Martin, Lisa W; Moore, Jason H; Morrison, Alanna C; Mosley, Thomas H; Ogunniyi, Adesola; Palmas, Walter; Papanicolaou, George; Penman, Alan; Polak, Joseph F; Ridker, Paul M; Salako, Babatunde; Singleton, Andrew B; Shriner, Daniel; Taylor, Kent D; Vasan, Ramachandran; Wiggins, Kerri; Williams, Scott M; Yanek, Lisa R; Zhao, Wei; Zonderman, Alan B; Becker, Diane M; Berenson, Gerald; Boerwinkle, Eric; Bottinger, Erwin; Cushman, Mary; Eaton, Charles; Nyberg, Fredrik; Heiss, Gerardo; Hirschhron, Joel N; Howard, Virginia J; Karczewsk, Konrad J; Lanktree, Matthew B; Liu, Kiang; Liu, Yongmei; Loos, Ruth; Margolis, Karen; Snyder, Michael; Psaty, Bruce M; Schork, Nicholas J; Weir, David R; Rotimi, Charles N; Sale, Michele M; Harris, Tamara; Kardia, Sharon L R; Hunt, Steven C; Arnett, Donna; Redline, Susan; Cooper, Richard S; Risch, Neil J; Rao, D C; Rotter, Jerome I; Chakravarti, Aravinda; Reiner, Alex P; Levy, Daniel; Keating, Brendan J; Zhu, Xiaofeng

    2013-09-05

    High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  19. Genome-wide Association Analysis of Blood-Pressure Traits in African-Ancestry Individuals Reveals Common Associated Genes in African and Non-African Populations

    PubMed Central

    Franceschini, Nora; Fox, Ervin; Zhang, Zhaogong; Edwards, Todd L.; Nalls, Michael A.; Sung, Yun Ju; Tayo, Bamidele O.; Sun, Yan V.; Gottesman, Omri; Adeyemo, Adebawole; Johnson, Andrew D.; Young, J. Hunter; Rice, Ken; Duan, Qing; Chen, Fang; Li, Yun; Tang, Hua; Fornage, Myriam; Keene, Keith L.; Andrews, Jeanette S.; Smith, Jennifer A.; Faul, Jessica D.; Guangfa, Zhang; Guo, Wei; Liu, Yu; Murray, Sarah S.; Musani, Solomon K.; Srinivasan, Sathanur; Velez Edwards, Digna R.; Wang, Heming; Becker, Lewis C.; Bovet, Pascal; Bochud, Murielle; Broeckel, Ulrich; Burnier, Michel; Carty, Cara; Chasman, Daniel I.; Ehret, Georg; Chen, Wei-Min; Chen, Guanjie; Chen, Wei; Ding, Jingzhong; Dreisbach, Albert W.; Evans, Michele K.; Guo, Xiuqing; Garcia, Melissa E.; Jensen, Rich; Keller, Margaux F.; Lettre, Guillaume; Lotay, Vaneet; Martin, Lisa W.; Moore, Jason H.; Morrison, Alanna C.; Mosley, Thomas H.; Ogunniyi, Adesola; Palmas, Walter; Papanicolaou, George; Penman, Alan; Polak, Joseph F.; Ridker, Paul M.; Salako, Babatunde; Singleton, Andrew B.; Shriner, Daniel; Taylor, Kent D.; Vasan, Ramachandran; Wiggins, Kerri; Williams, Scott M.; Yanek, Lisa R.; Zhao, Wei; Zonderman, Alan B.; Becker, Diane M.; Berenson, Gerald; Boerwinkle, Eric; Bottinger, Erwin; Cushman, Mary; Eaton, Charles; Nyberg, Fredrik; Heiss, Gerardo; Hirschhron, Joel N.; Howard, Virginia J.; Karczewsk, Konrad J.; Lanktree, Matthew B.; Liu, Kiang; Liu, Yongmei; Loos, Ruth; Margolis, Karen; Snyder, Michael; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young; Jeon, Jae-Pil; Kim, Sung Soo; Han, Bok-Ghee; Cho, Yoon Shin; Sim, Xueling; Tay, Wan Ting; Ong, Rick Twee Hee; Seielstad, Mark; Liu, Jian Jun; Aung, Tin; Wong, Tien Yin; Teo, Yik Ying; Tai, E. Shyong; Chen, Chien-Hsiun; Chang, Li-ching; Chen, Yuan-Tsong; Wu, Jer-Yuarn; Kelly, Tanika N.; Gu, Dongfeng; Hixson, James E.; Sung, Yun Ju; He, Jiang; Tabara, Yasuharu; Kokubo, Yoshihiro; Miki, Tetsuro; Iwai, Naoharu; Kato, Norihiro; Takeuchi, Fumihiko; Katsuya, Tomohiro; Nabika, Toru; Sugiyama, Takao; Zhang, Yi; Huang, Wei; Zhang, Xuegong; Zhou, Xueya; Jin, Li; Zhu, Dingliang; Psaty, Bruce M.; Schork, Nicholas J.; Weir, David R.; Rotimi, Charles N.; Sale, Michele M.; Harris, Tamara; Kardia, Sharon L.R.; Hunt, Steven C.; Arnett, Donna; Redline, Susan; Cooper, Richard S.; Risch, Neil J.; Rao, D.C.; Rotter, Jerome I.; Chakravarti, Aravinda; Reiner, Alex P.; Levy, Daniel; Keating, Brendan J.; Zhu, Xiaofeng

    2013-01-01

    High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10−8) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability. PMID:23972371

  20. Association Analysis of Two Single-Nucleotide Polymorphisms of the RELN Gene with Autism in the South African Population

    PubMed Central

    Sharma, Jyoti Rajan; Gameeldien, Hajirah; Davids, Muneera; Kaur, Mandeep; van der Merwe, Lize

    2013-01-01

    Background: Autism (MIM209850) is a neurodevelopmental disorder characterized by a triad of impairments, namely impairment in social interaction, impaired communication skills, and restrictive and repetitive behavior. A number of family and twin studies have demonstrated that genetic factors play a pivotal role in the etiology of autistic disorder. Various reports of reduced levels of reelin protein in the brain and plasma in autistic patients highlighted the role of the reelin gene (RELN) in autism. There is no such published study on the South African (SA) population. Aims: The aim of the present study was to find the genetic association of intronic rs736707 and exonic rs362691 (single-nucleotide polymorphisms [SNPs] of the RELN gene) with autism in a SA population. Methods: Genomic DNA was isolated from cheek cell swabs from autistic (136) as well as control (208) subjects. The TaqMan® Real-Time polymerase chain reaction and genotyping assay was utilized to determine the genotypes. Results: A significant association of SNP rs736707, but not for SNP rs362691, with autism in the SA population is observed. Conclusion: There might be a possible role of RELN in autism, especially for SA populations. The present study represents the first report on genetic association studies on the RELN gene in the SA population. PMID:23216241

  1. Association analysis of two single-nucleotide polymorphisms of the RELN gene with autism in the South African population.

    PubMed

    Sharma, Jyoti Rajan; Arieff, Zainunisha; Gameeldien, Hajirah; Davids, Muneera; Kaur, Mandeep; van der Merwe, Lize

    2013-02-01

    Autism (MIM209850) is a neurodevelopmental disorder characterized by a triad of impairments, namely impairment in social interaction, impaired communication skills, and restrictive and repetitive behavior. A number of family and twin studies have demonstrated that genetic factors play a pivotal role in the etiology of autistic disorder. Various reports of reduced levels of reelin protein in the brain and plasma in autistic patients highlighted the role of the reelin gene (RELN) in autism. There is no such published study on the South African (SA) population. The aim of the present study was to find the genetic association of intronic rs736707 and exonic rs362691 (single-nucleotide polymorphisms [SNPs] of the RELN gene) with autism in a SA population. Genomic DNA was isolated from cheek cell swabs from autistic (136) as well as control (208) subjects. The TaqMan(®) Real-Time polymerase chain reaction and genotyping assay was utilized to determine the genotypes. A significant association of SNP rs736707, but not for SNP rs362691, with autism in the SA population is observed. There might be a possible role of RELN in autism, especially for SA populations. The present study represents the first report on genetic association studies on the RELN gene in the SA population.

  2. Meta-analysis indicates that SNP rs9939609 within FTO is not associated with major depressive disorder (MDD) in Asian population.

    PubMed

    Yao, Yao; Wen, Yueqiang; Du, Tingfu; Sun, Ning; Deng, Hong; Ryan, Joanne; Rao, Shuquan

    2016-03-15

    Major depressive disorder (MDD) is one of the most prevalent psychiatric illnesses with heritability of up to 38%. The fat mass- and obesity-associated (FTO) gene, in particular the single nucleotide polymorphism (SNP) rs9939609, has been identified as a genetic risk loci associated with MDD. However, most prior studies have involved European and American populations. Whether rs9939609 is an true risk SNP for MDD in Asian populations remains inconclusive. In the present study, we conducted a meta-analysis of the association between rs9939609 and MDD in Asian populations by combining 5 available case-control samples totaling 6531 cases and 12,359 controls. Our meta-analysis suggests that rs9939609 is not a risk SNP for MDD in Asian populations by fixed effect model (Z=1.04, P=0.30, OR=0.96, 95% CI=0.90-1.03). The age distribution and gender ratios were not matched well in the combined samples of cases and controls. Publication bias might be also considered with only a relatively small number of association studies of FTO rs9939609 with MDD in Asian populations. The absence of association of rs9939609 with MDD in our Asian populations suggests a potential genetic heterogeneity in the susceptibility of MDD on this locus. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Association between tobacco plain packaging and Quitline calls: a population-based, interrupted time-series analysis.

    PubMed

    Young, Jane M; Stacey, Ingrid; Dobbins, Timothy A; Dunlop, Sally; Dessaix, Anita L; Currow, David C

    2014-01-20

    To investigate whether the introduction of tobacco plain packaging in Australia from 1 October 2012 was associated with a change in the number of calls to the smoking cessation helpline, Quitline, and to compare this with the impact of the introduction of graphic health warnings from 1 March 2006. Whole-of-population interrupted time-series analysis in New South Wales and the Australian Capital Territory between 1 March 2005 and October 2006 for the comparator, graphic health warnings, and October 2011 and April 2013 for the intervention of interest, tobacco plain packaging. Weekly number of calls to the Quitline, after adjusting for seasonal trends, anti-tobacco advertising, cigarette costliness and the number of smokers in the community. There was a 78% increase in the number of calls to the Quitline associated with the introduction of plain packaging (baseline, 363/week; peak, 651/week [95% CI, 523-780/week; P < 0.001]). This peak occurred 4 weeks after the initial appearance of plain packaging and has been prolonged. The 2006 introduction of graphic health warnings had the same relative increase in calls (84%; baseline, 910/week; peak, 1673/week [95% CI, 1383-1963/week; P < 0.001]) but the impact of plain packaging has continued for longer. There has been a sustained increase in calls to the Quitline after the introduction of tobacco plain packaging. This increase is not attributable to anti-tobacco advertising activity, cigarette price increases nor other identifiable causes. This is an important incremental step in comprehensive tobacco control.

  4. Common variant of PDZ domain containing 1 (PDZK1) gene is associated with gout susceptibility: A replication study and meta-analysis in Japanese population.

    PubMed

    Higashino, Toshihide; Matsuo, Hirotaka; Sakiyama, Masayuki; Nakayama, Akiyoshi; Nakamura, Takahiro; Takada, Tappei; Ogata, Hiraku; Kawamura, Yusuke; Kawaguchi, Makoto; Naito, Mariko; Kawai, Sayo; Takada, Yuzo; Ooyama, Hiroshi; Suzuki, Hiroshi; Shinomiya, Nariyoshi

    2016-12-01

    PDZ domain containing 1 (PDZK1) is a scaffold protein that organizes a transportsome and regulates several transporters' functions including urate and drug transporters. Therefore, PDZK1 in renal proximal tubules may affect serum uric acid levels through PDZK1-binding renal urate transporters. Two previous studies in Japanese male population reported that a PDZK1 single nucleotide polymorphism (SNP), rs12129861, was not associated with gout. In the present study, we performed a further association analysis between gout and rs12129861 in a different large-scale Japanese male population and a meta-analysis with previous Japanese population studies. We genotyped rs12129861 in 1210 gout cases and 1224 controls of a Japanese male population by TaqMan assay. As a result, we showed that rs12129861 was significantly associated with gout susceptibility (P = 0.016, odds ratio [OR] = 0.80, 95% confidence interval [CI] 0.67-0.96). The result of the meta-analysis among Japanese populations also showed a significant association (P = 0.013, OR = 0.85, 95%CI 0.75-0.97). Our findings show the significant association between gout susceptibility and common variant of PDZK1 which reportedly regulates the functions of urate transporters in the urate transportsome. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  5. Association studies in consanguineous populations

    SciTech Connect

    Genin, E.; Clerget-Darpous, F.

    1996-04-01

    To study the genetic determinism of multifactorial diseases in large panmictic populations, a strategy consists in looking for an association with markers closely linked to candidate genes. A distribution of marker genotypes different in patients and controls may indicate that the candidate gene is involved in the disease. In panmictic populations, the power to detect the role of a candidate gene depends on the gametic disequilibrium with the marker locus. In consanguineous populations, we show that it depends on the inbreeding coefficient F as well. Inbreeding increases the power to detect the role of a recessive or quasi-recessive disease-susceptibility factor. The gain in power turns out to be greater for small values of the gametic disequilibrium. Moreover, even in the absence of gametic disequilibrium, the presence of inbreeding may allow to detect the role of a recessive factor. Ignoring inbreeding when it exists may lead to reject falsely a recessive model if the mode of inheritance is inferred on the distribution of genotypes among patients. 5 refs., 6 figs., 1 tab.

  6. [Spatial pattern analysis and associations of Quercus aquifolioides population at different growth stages in Southeast Tibet, China].

    PubMed

    Shen, Zhi-qiang; Hua, Min; Dan, Qu; Lu, Jie; Fang, Jiang-ping

    2016-02-01

    This article analyzed the spatial pattern and its correlation of Quercus aquifolioides, Southeast Tibet at different growing stages by using Ripley' s L function in the method of point pattern, analysis. The results showed the diameter structure of Q. aquifolioides population in Southeast Tibet followed a 'single peak' shape and the saplings and medium trees predominated in number in the whole population. The population had a high regeneration rate and was of increase type. In the growth process of Q. aquifolioides from saplings to large trees, saplings and medium trees showed aggregation distribution at.small scale, while large trees showed basically random distribution at whole scale. There was significant correlation between saplings with medium or large trees at small scale, however, there was no correlation between medium and large trees. In the growth process of Q. aquifolioides population from saplings, medium trees to large trees, its spatial pattern developed from aggregative distribution to random distribution. The natural regeneration of Q. aquifolioides population was affected not only by interspecific competition, but also by intraspecific competition. In the similar natural environment, the most important factors affecting the spatial pattern of Q. aquifoioides population were its own biological and ecological characteristics.

  7. Association of Climatic Variability, Vector Population and Malarial Disease in District of Visakhapatnam, India: A Modeling and Prediction Analysis

    PubMed Central

    Srimath-Tirumula-Peddinti, Ravi Chandra Pavan Kumar; Neelapu, Nageswara Rao Reddy; Sidagam, Naresh

    2015-01-01

    Background Malarial incidence, severity, dynamics and distribution of malaria are strongly determined by climatic factors, i.e., temperature, precipitation, and relative humidity. The objectives of the current study were to analyse and model the relationships among climate, vector and malaria disease in district of Visakhapatnam, India to understand malaria transmission mechanism (MTM). Methodology Epidemiological, vector and climate data were analysed for the years 2005 to 2011 in Visakhapatnam to understand the magnitude, trends and seasonal patterns of the malarial disease. Statistical software MINITAB ver. 14 was used for performing correlation, linear and multiple regression analysis. Results/Findings Perennial malaria disease incidence and mosquito population was observed in the district of Visakhapatnam with peaks in seasons. All the climatic variables have a significant influence on disease incidence as well as on mosquito populations. Correlation coefficient analysis, seasonal index and seasonal analysis demonstrated significant relationships among climatic factors, mosquito population and malaria disease incidence in the district of Visakhapatnam, India. Multiple regression and ARIMA (I) models are best suited models for modeling and prediction of disease incidences and mosquito population. Predicted values of average temperature, mosquito population and malarial cases increased along with the year. Developed MTM algorithm observed a major MTM cycle following the June to August rains and occurring between June to September and minor MTM cycles following March to April rains and occurring between March to April in the district of Visakhapatnam. Fluctuations in climatic factors favored an increase in mosquito populations and thereby increasing the number of malarial cases. Rainfall, temperatures (20°C to 33°C) and humidity (66% to 81%) maintained a warmer, wetter climate for mosquito growth, parasite development and malaria transmission. Conclusions

  8. Identifying associated factors with social capital using path analysis: A population-based survey in Tehran, Iran (Urban HEART-2).

    PubMed

    Asadi-Lari, Mohsen; Hassanzadeh, Jafar; Torabinia, Mansour; Vaez-Mahdavi, Mohammad Reza; Montazeri, Ali; Ghaem, Haleh; Menati, Rostam; Niazi, Mohsen; Kassani, Aziz

    2016-01-01

    Background: Social capital has been defined as norms, networks, and social links that facilitate collective actions. Social capital is related to a number of main social and public health variables. Therefore, the present study aimed to determine the factors associated with social capital among the residents of Tehran, Iran. Methods: In this large cross-sectional population-based study, 31531 residents aged 20 years and above were selected through multi-stage sampling method from 22 districts of Tehran in 2011. The social capital questionnaire, 28-item General Health Questionnaire (GHQ-28), and Short-Form Health Survey (SF-12) were used. Hypothetical causal models were designed to identify the pathways through which different variables influenced the components of social capital. Then, path analysis was conducted for identifying the determinants of social capital. Results: The most influential variables in 'individual trust' were job status (β=0.37, p=0.02), marital status (β=0.32, p=0.01), Physical Component Summary (PCS) (β=0.37, p=0.02), and age (β=0.34, p=0.03). On the other hand, education level (β=0.34, p=0.01), age (β=0.33, p=0.02), marital status (β=0.33, p=0.01), and job status (β=0.32, p=0.01) were effective in 'cohesion and social support'. Additionally, age (β=0.18, p=0.02), PCS (β=0.36, p=0.01), house ownership (β=0.23, p=0.03), and mental health (β=0.26, p=0.01) were influential in 'social trust/collective relations'. Conclusion: Social capital can be improved in communities by planning to improve education and occupation status, paying more attention to strengthening family bonds, and provision of local facilities and neighborhood bonds to reduce migration within the city.

  9. Prevalence of atrial fibrillation and its associated factors in Spain: An analysis of 6 population-based studies. DARIOS Study.

    PubMed

    Baena-Díez, J M; Grau, M; Forés, R; Fernández-Bergés, D; Elosua, R; Sorribes, M; Félix-Redondo, F J; Segura, A; Rigo, F; Cabrera de León, A; Sanz, H; Marrugat, J; Sala, J

    2014-12-01

    Atrial fibrillation (AF) is the most common type of arrhythmia. The purpose of this study was to determine the prevalence of atrial fibrillation and its relationship with cardiovascular risk factors in Spain. Cross-sectional study based on a grouped analysis of 17,291 randomized individuals recruited in 6 population studies. The prevalence of atrial fibrillation was 1.5% (95% CI:1.3-1.7%). Men had a greater prevalence of the disease than women (1.9 vs. 1.1%, respectively). The prevalence of atrial fibrillation progressively increased with age: 0.05% for patients younger than 45 years, 0.5% for those between 45-59 years of age, 2.3% for those between 60-74 years of age and 6.3% for those older than 75 years. The percentage of individuals who were underwent anticoagulant treatment was 74.3%. The risk factors significantly associated with arrhythmia were an age older than 60 years (odds ratio [OR]: 7.6; 95% CI: 5.1-11.2), the male sex (OR:1.8; 95% CI: 1.4-2.4), arterial hypertension (OR:1.6; 95% CI: 1.2-2.1), obesity (OR:1.5; 95% CI:1.2-2.1) and a history of coronary artery disease (OR:1.9; 95% CI: 1.3-3.0). Atrial fibrillation is a common disease in elderly individuals, while its prevalence is low in individuals younger than 60 years. Most individuals with atrial fibrillation were on anticoagulant treatment. The risk factors for this type of arrhythmia are age, the male sex, hypertension, obesity and a history of coronary artery disease. Copyright © 2014. Published by Elsevier Espana.

  10. Identifying associated factors with social capital using path analysis: A population-based survey in Tehran, Iran (Urban HEART-2)

    PubMed Central

    Asadi-Lari, Mohsen; Hassanzadeh, Jafar; Torabinia, Mansour; Vaez-Mahdavi, Mohammad Reza; Montazeri, Ali; Ghaem, Haleh; Menati, Rostam; Niazi, Mohsen; Kassani, Aziz

    2016-01-01

    Background: Social capital has been defined as norms, networks, and social links that facilitate collective actions. Social capital is related to a number of main social and public health variables. Therefore, the present study aimed to determine the factors associated with social capital among the residents of Tehran, Iran. Methods: In this large cross-sectional population-based study, 31531 residents aged 20 years and above were selected through multi-stage sampling method from 22 districts of Tehran in 2011. The social capital questionnaire, 28-item General Health Questionnaire (GHQ-28), and Short-Form Health Survey (SF-12) were used. Hypothetical causal models were designed to identify the pathways through which different variables influenced the components of social capital. Then, path analysis was conducted for identifying the determinants of social capital. Results: The most influential variables in ‘individual trust’ were job status (β=0.37, p=0.02), marital status (β=0.32, p=0.01), Physical Component Summary (PCS) (β=0.37, p=0.02), and age (β=0.34, p=0.03). On the other hand, education level (β=0.34, p=0.01), age (β=0.33, p=0.02), marital status (β=0.33, p=0.01), and job status (β=0.32, p=0.01) were effective in ‘cohesion and social support’. Additionally, age (β=0.18, p=0.02), PCS (β=0.36, p=0.01), house ownership (β=0.23, p=0.03), and mental health (β=0.26, p=0.01) were influential in ‘social trust/collective relations’. Conclusion: Social capital can be improved in communities by planning to improve education and occupation status, paying more attention to strengthening family bonds, and provision of local facilities and neighborhood bonds to reduce migration within the city. PMID:28210579

  11. Genetic diversity, population structure and genome-wide marker-trait association analysis of the USDA pea (Pisum sativum L.) core collection

    USDA-ARS?s Scientific Manuscript database

    Genetic diversity, population structure and genome-wide marker-trait association analysis was conducted for the USDA pea (Pisum sativum L.) core collection. The core collection contained 285 accessions with diverse phenotypes and geographic origins. The 137 DNA markers included 102 polymorphic fra...

  12. Association between 12p13 SNPs rs11833579/rs12425791 near NINJ2 gene and ischemic stroke in East Asian population: evidence from a meta-analysis.

    PubMed

    Li, Bing-Hu; Zhang, Li-Li; Yin, Yan-Wei; Pi, Yan; Guo, Lu; Yang, Qing-Wu; Gao, Chang-Yue; Fang, Chuan-Qin; Wang, Jing-Zhou; Li, Jing-Cheng

    2012-05-15

    Meta-analysis in European population found no association between rs12425791/rs11833579 and ischemic stroke. Several studies focused on East Asians have evaluated the association between this two SNPs and risk of ischemic stroke, but the results have been inconsistent. The aim of this study was to perform a meta-analysis to investigate a more authentic association between rs12425791 and rs11833579 G>A mutation and ischemic stroke in East Asian population, as well as in Chinese Han population. Systematic searches of electronic databases Embase, PubMed, Web of Science, and CBM as well as hand searching of the references of identified articles and the meeting abstracts were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were performed using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Different effects models were used according to the difference in heterogeneity. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 4 publications including 7 studies were involved. For rs12425791, significant association was found in allelic model (OR=1.06, 95%CI=1.00-1.11) and dominant model (OR=1.10, 95%CI=1.03-1.18), whereas no evidence of association was found for additive model (OR=1.04, 95%CI=0.93-1.17) and for recessive model (OR=0.99, 95%CI=0.88-1.10). For rs11833579, no evidence of association was found for all genetic models. In the analysis of Chinese Han population, there is lack of evidence for association of ischemic stroke for both SNPs. In summary, our meta-analysis suggests that rs12425791 is significantly associated with ischemic stroke in East Asian population but not Chinese Han population, of which A alleles increase the risk of ischemic stroke, whereas no evidence of association was found for rs11833579 in East Asian population as well as Chinese Han population. Copyright

  13. MicroRNA Genetic Variation: From Population Analysis to Functional Implications of Three Allele Variants Associated with Cancer.

    PubMed

    Torruella-Loran, Ignasi; Laayouni, Hafid; Dobon, Begoña; Gallego, Alicia; Balcells, Ingrid; Garcia-Ramallo, Eva; Espinosa-Parrilla, Yolanda

    2016-10-01

    Nucleotide variants in microRNA regions have been associated with disease; nevertheless, few studies still have addressed the allele-dependent effect of these changes. We studied microRNA genetic variation in human populations and found that while low-frequency variants accumulate indistinctly in microRNA regions, the mature and seed regions tend to be depleted of high-frequency variants, probably as a result of purifying selection. Comparison of pairwise population fixation indexes among regions showed that the seed had higher population fixation indexes than the other regions, suggesting the existence of local adaptation in the seed region. We further performed functional studies of three microRNA variants associated with cancer (rs2910164:C > G in MIR146A, rs11614913:C > T in MIR196A2, and rs3746444:A > G in both MIR499A and MIR499B). We found differences in the expression between alleles and in the regulation of several genes involved in cancer, such as TP53, KIT, CDH1, CLH, and TERT, which may result in changes in regulatory networks related to tumorigenesis. Furthermore, luciferase-based assays showed that MIR499A could be regulating the cadherin CDH1 and the cell adhesion molecule CLH1 in an allele-dependent fashion. A better understanding of the effect of microRNA variants associated with disease could be key in our way to a more personalized medicine.

  14. Combining family- and population-based imputation data for association analysis of rare and common variants in large pedigrees.

    PubMed

    Saad, Mohamad; Wijsman, Ellen M

    2014-11-01

    In the last two decades, complex traits have become the main focus of genetic studies. The hypothesis that both rare and common variants are associated with complex traits is increasingly being discussed. Family-based association studies using relatively large pedigrees are suitable for both rare and common variant identification. Because of the high cost of sequencing technologies, imputation methods are important for increasing the amount of information at low cost. A recent family-based imputation method, Genotype Imputation Given Inheritance (GIGI), is able to handle large pedigrees and accurately impute rare variants, but does less well for common variants where population-based methods perform better. Here, we propose a flexible approach to combine imputation data from both family- and population-based methods. We also extend the Sequence Kernel Association Test for Rare and Common variants (SKAT-RC), originally proposed for data from unrelated subjects, to family data in order to make use of such imputed data. We call this extension "famSKAT-RC." We compare the performance of famSKAT-RC and several other existing burden and kernel association tests. In simulated pedigree sequence data, our results show an increase of imputation accuracy from use of our combining approach. Also, they show an increase of power of the association tests with this approach over the use of either family- or population-based imputation methods alone, in the context of rare and common variants. Moreover, our results show better performance of famSKAT-RC compared to the other considered tests, in most scenarios investigated here.

  15. Polymorphism analysis in estrogen receptors alpha and beta genes and their association with infertile population in Pakistan

    PubMed Central

    Liaqat, Sinha; Hasnain, Shahida; Muzammil, Saima; Hayat, Sumreen

    2015-01-01

    Studies on polymorphism of estrogen receptor (ESR) alpha and beta genes have been mostly implicated in infertility, but the results have been controversial due to lack of comprehensive data. The present study focused on association of ESR genes with both male and female infertility. In ESRα, PvuII (rs2234693) and XbaI (rs9340799) were studied while in ESRβ gene, risk of infertility was determined for silent G/A RsaI (rs1256049) polymorphism. Total 124 subjects (74 cases and 50 controls) were part of this study having primary infertility. Restriction fragment length polymorphism (RFLP) was performed with PvuII, XbaI and RsaI to determine polymorphism. Correlation between age and follicle stimulating hormone (FSH) of cases and controls was determined and no association was found between infertility and FSH hormone. Heterozygous AG genotype of XbaI polymorphism (P= 2.505e-06) and heterozygous TC genotype (P= 0.00003) in PvuII polymorphism were strongly associated with risk of infertility. In ESRβ gene, there was lack of polymorphism for RsaI in our population as all subjects were homozygous (GG). Haplotype frequencies showed that XbaI and PvuII polymorphisms are in strong linkage disequilibrium. This study shows that in our population XbaI and PvuII polymorphisms of ESRα are associated with risk of infertility. PMID:27065769

  16. Genetic association of COL1A1 polymorphisms with high myopia in Asian population: a Meta-analysis

    PubMed Central

    Gong, Bo; Qu, Chao; Huang, Xiao-Fang; Ye, Zi-Meng; Zhang, Ding-Ding; Shi, Yi; Chen, Rong; Liu, Yu-Ping; Shuai, Ping

    2016-01-01

    AIM To comprehensively evaluate the potential association of COL1A1 polymorphisms with high myopia by a systematic review and Meta-analysis. METHODS All association studies on COL1A1 and high myopia reported up to June 10, 2014 in PubMed, Embase, Web of Science, and the Chinese Biomedical Database were retrieved. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were analyzed for single-nucleotide polymorphisms (SNPs) using fixed- and random- effects models according to between-study heterogeneity. Publication bias analyses were conducted by Egger's test. RESULTS A total of four studies from reported papers were included in this analysis. The Meta-analyses for COL1A1 rs2075555, composed of 2304 high myopia patients and 2272 controls, failed to detect any significant association with high myopia. A total of 971 cases and 649 controls were tested for COL1A1 rs2269336. The association of COL1A1 rs2269336 with high myopia was observed in recessive model (CC vs CG+GG, P=0.03) and in heterozygous model (CG vs GG, P=0.04), but not in other models. CONCLUSION This Meta-analysis shows that COL1A1 rs2269336 (CC vs CG+GG) affects individual susceptibility to high myopia, whereas there is no association detected between SNPs rs2075555 and high myopia. Given the limited sample size, further investigations including more ethnic groups are required to validate the association. PMID:27588274

  17. Polymorphisms in peptidylarginine deiminase associate with rheumatoid arthritis in diverse Asian populations: evidence from MyEIRA study and meta-analysis.

    PubMed

    Too, Chun Lai; Murad, Shahnaz; Dhaliwal, Jasbir Singh; Larsson, Per; Jiang, Xia; Ding, Bo; Alfredsson, Lars; Klareskog, Lars; Padyukov, Leonid

    2012-11-19

    The majority of our knowledge regarding disease-related mechanisms of uncontrolled citrullination and anti-citrullinated protein antibody development in rheumatoid arthritis (RA) was investigated in Caucasian populations. However, peptidylarginine deiminase (PADI) type 4 gene polymorphisms are associated with RA in East Asian populations and weak or no association was found in Caucasian populations. This study explores the association between the PADI4 polymorphisms and RA risk in a multiethnic population residing in South East Asia with the goal of elucidating generalizability of association in non-Caucasian populations. A total of 320 SNPs from the PADI locus (including PADI1, PADI2, PADI3, PADI4 and PADI6 genes) were genotyped in 1,238 RA cases and 1,571 control subjects from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) case-control study. Additionally, we conducted meta-analysis of our data together with the previously published studies of RA from East Asian populations. The overall odds ratio (ORoverall) for the PADI4 (rs2240340) allelic model was 1.11 (95% confidence interval (CI) = 1.00 to 1.23, P = 0.04) and for the genotypic model was 1.20 (95% CI = 1.01 to 1.44, P = 0.04). Haplotype analysis for four selected PADI4 SNPs revealed a significant association of one with susceptibility (P = 0.001) and of another with a protective effect (P = 0.02). The RA susceptibility was further confirmed when combined meta-analysis was performed using these data together with data from five previously published studies from Asia comprising 5,192 RA cases and 4,317 control subjects (ORoverall = 1.23 (95% CI = 1.16 to 1.31, Pheterogeneity = 0.08) and 1.31 (95% CI = 1.20 to 1.44, Pheterogeneity = 0.32) in allele and genotype-based models, respectively). In addition, we also detected a novel association of PADI2 genetic variant rs1005753 with RA (ORoverall = 0.87 (95% CI = 0.77 to 0.99)). Our study demonstrates an association between PADI4 and

  18. Polymorphisms in peptidylarginine deiminase associate with rheumatoid arthritis in diverse Asian populations: evidence from MyEIRA study and meta-analysis

    PubMed Central

    2012-01-01

    Introduction The majority of our knowledge regarding disease-related mechanisms of uncontrolled citrullination and anti-citrullinated protein antibody development in rheumatoid arthritis (RA) was investigated in Caucasian populations. However, peptidylarginine deiminase (PADI) type 4 gene polymorphisms are associated with RA in East Asian populations and weak or no association was found in Caucasian populations. This study explores the association between the PADI4 polymorphisms and RA risk in a multiethnic population residing in South East Asia with the goal of elucidating generalizability of association in non-Caucasian populations. Methods A total of 320 SNPs from the PADI locus (including PADI1, PADI2, PADI3, PADI4 and PADI6 genes) were genotyped in 1,238 RA cases and 1,571 control subjects from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) case-control study. Additionally, we conducted meta-analysis of our data together with the previously published studies of RA from East Asian populations. Results The overall odds ratio (ORoverall) for the PADI4 (rs2240340) allelic model was 1.11 (95% confidence interval (CI) = 1.00 to 1.23, P = 0.04) and for the genotypic model was 1.20 (95% CI = 1.01 to 1.44, P = 0.04). Haplotype analysis for four selected PADI4 SNPs revealed a significant association of one with susceptibility (P = 0.001) and of another with a protective effect (P = 0.02). The RA susceptibility was further confirmed when combined meta-analysis was performed using these data together with data from five previously published studies from Asia comprising 5,192 RA cases and 4,317 control subjects (ORoverall = 1.23 (95% CI = 1.16 to 1.31, Pheterogeneity = 0.08) and 1.31 (95% CI = 1.20 to 1.44, Pheterogeneity = 0.32) in allele and genotype-based models, respectively). In addition, we also detected a novel association of PADI2 genetic variant rs1005753 with RA (ORoverall = 0.87 (95% CI = 0.77 to 0.99)). Conclusion Our study

  19. Associations of ACE I/D, AGT M235T gene polymorphisms with pregnancy induced hypertension in Chinese population: a meta-analysis.

    PubMed

    Zhu, Ming; Zhang, Jie; Nie, Shaofa; Yan, Weirong

    2012-09-01

    There have been many studies concerning the associations of angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T polymorphisms with pregnancy induced hypertension (PIH) among Chinese populations. However, the results were inconsistent, prompting the necessity of meta-analysis. Studies published in English and Chinese were mainly searched in EMbase, PubMed and CBM up to January 2012. Twenty-three studies with 3,551 subjects for ACE I/D and seven studies with 1,296 subjects for AGT M235T were included. Significant associations were found between ACE I/D and PIH under dominant, recessive and allelic models. A separate analysis confined to preeclampsia suggested that ACE I/D was associated with preeclampsia under recessive model and allelic model, but not dominant model. Stratified analyses were conducted as meta-regression analysis indicated that the sample size of case group was a significant source of heterogeneity, which suggested no significant association between ACE I/D and PIH in the subgroup of more than 100 cases. Associations were found between AGT M235T and PIH under dominant genetic model (OR = 1.59; 95 %CI: 1.04-2.42), recessive genetic model (OR = 1.60; 95 %CI: 1.07-2.40), and allelic model (OR = 1.40; 95 %CI: 1.17-1.68). No publication bias was found in either meta-analysis. The present meta-analysis suggested significant associations between ACE I/D, AGT M235T and PIH in Chinese populations. However, no significant association was found between ACE I/D and PIH in the subgroup of more than 100 cases. Studies with larger sample sizes are necessary to investigate the associations between gene polymorphisms and PIH in Chinese populations.

  20. Analysis of the association between the LUM rs3759223 variant and high myopia in a Japanese population

    PubMed Central

    Okui, Shintaro; Meguro, Akira; Takeuchi, Masaki; Yamane, Takahiro; Okada, Eiichi; Iijima, Yasuhito; Mizuki, Nobuhisa

    2016-01-01

    Purpose Many studies have investigated the relationship of the lumican gene (LUM) rs3759223 variant with the risk of high myopia, but the results have been inconsistent and inconclusive. In this study, we investigated whether LUM rs3759223 is associated with high myopia in a Japanese population. Methods We recruited 1,585 Japanese patients with high myopia (spherical equivalent [SE] <−9.00 diopters [D]) and 1,011 Japanese healthy controls (SE ≥−1.00 D). The rs3759223 variant was genotyped using the TaqMan assay, and the allelic and genotypic diversity among cases and controls was analyzed according to the SE level. Results In the allelic tests, the odds ratio (OR) for the T allele of rs3759223 tended to increase with the progression of SE, and the highest OR (1.56) was found in patients with SE <−15 D in both eyes. The OR of the T allele tended to increase with the progression of SE in the additive, dominant, and recessive inheritance models. However, we found no significant associations for any of the alleles or genotype models. Conclusion These data support the possibility that the LUM rs3759223 T allele accelerates the progression of SE in the Japanese population, although no significant associations were observed in this study. Additional genetic studies with larger samples that take into account the degree of SE are needed to clarify the contribution of rs3759223 to the risk of high myopia. PMID:27826181

  1. Molecular taxonomic analysis of the plant associations of adult pollen beetles (Nitidulidae: Meligethinae), and the population structure of Brassicogethes aeneus.

    PubMed

    Ouvrard, Pierre; Hicks, Damien M; Mouland, Molly; Nicholls, James A; Baldock, Katherine C R; Goddard, Mark A; Kunin, William E; Potts, Simon G; Thieme, Thomas; Veromann, Eve; Stone, Graham N

    2016-12-01

    Pollen beetles (Nitidulidae: Meligethinae) are among the most abundant flower-visiting insects in Europe. While some species damage millions of hectares of crops annually, the biology of many species is little known. We assessed the utility of a 797 base pair fragment of the cytochrome oxidase 1 gene to resolve molecular operational taxonomic units (MOTUs) in 750 adult pollen beetles sampled from flowers of 63 plant species sampled across the UK and continental Europe. We used the same locus to analyse region-scale patterns in population structure and demography in an economically important pest, Brassicogethes aeneus. We identified 44 Meligethinae at ∼2% divergence, 35 of which contained published sequences. A few specimens could not be identified because the MOTUs containing them included published sequences for multiple Linnaean species, suggesting either retention of ancestral haplotype polymorphism or identification errors in published sequences. Over 90% of UK specimens were identifiable as B. aeneus. Plant associations of adult B. aeneus were found to be far wider taxonomically than for their larvae. UK B. aeneus populations showed contrasting affiliations between the north (most similar to Scandinavia and the Baltic) and south (most similar to western continental Europe), with strong signatures of population growth in the south.

  2. Associations between two polymorphisms (FokI and BsmI) of vitamin D receptor gene and type 1 diabetes mellitus in Asian population: a meta-analysis.

    PubMed

    Wang, Guofeng; Zhang, Qingqing; Xu, Ning; Xu, Kuanfeng; Wang, Jian; He, Wei; Yang, Tao

    2014-01-01

    Vitamin D receptor (VDR) gene polymorphisms are possibly involved in the development of type 1 diabetes mellitus (T1DM). However, the results to date have been inconclusive. We performed a meta-analysis to examine the association between 2 polymorphisms (FokI and BsmI) of the VDR gene and T1DM in the Asian population. Literature was retrieved from PubMed, Web of Science, CBM, Embase and Chinese databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random or fixed effect model. In total, 20 papers (BsmI: 13 studies; FokI: 13 studies) were included. In contrast to the FokI polymorphism, the BsmI polymorphism was associated with an increased risk of T1DM in the Asian population (OR = 1.47, 95% CI = 1.13-1.91, P = 0.004 for B vs. b). Upon stratification by regional geography, an increased risk of T1DM in association with the BsmI polymorphism was observed in the East Asian population (OR = 1.97, 95% CI = 1.38-2.83, P<0.001 for B vs. b), whereas the FokI polymorphism was associated with an increased risk of T1DM in the West Asian population (OR = 1.45, 95% CI = 1.12-1.88, P = 0.004 for F vs. f). Our meta-analysis suggests that the BsmI polymorphism may be a risk factor for susceptibility to T1DM in the East Asian population, and the FokI polymorphism is associated with an increased risk of T1DM in the West Asian population. However, because the study size was limited, further studies are essential to confirm our results.

  3. Association of chromosome 9p21 genetic variants with risk of coronary heart disease in the East Asian population: a meta-analysis.

    PubMed

    Dong, Liping; Wang, Haoran; Wang, Dao Wen; Ding, Hu

    2013-05-01

    Our aim was to evaluate the effect of SNPs in the 9p21 locus on genetic susceptibility of coronary heart disease in the East Asian population. We searched PubMed, EMBASE and CNKI for publications relating to the association between SNPs within the 9p21 locus and coronary heart disease in the East Asian population. This meta-analysis was assessed by STATA 9.2. Twenty-one studies from 15 eligible papers composing 25,945 cases and 31,777 control subjects were included in the meta-analysis. The odds ratio (OR) and 95% confidence interval (CI) for the risk allele was 1.30 (1.25-1.35) with moderate heterogeneity. No publication bias was observed in this study. Sensitivity analysis further strengthened the validity of this association. In conclusion, SNPs within the 9p21 locus were strongly associated with the risk of coronary heart disease in the East Asian population with a similar risk OR to the Caucasian population. © 2013 Blackwell Publishing Ltd/University College London.

  4. Genome-Wide Association Analysis of Meat Quality Traits in a Porcine Large White × Minzhu Intercross Population

    PubMed Central

    Luo, Weizhen; Cheng, Duxue; Chen, Shaokang; Wang, Ligang; Li, Yong; Ma, Xiaojun; Song, Xin; Liu, Xin; Li, Wen; Liang, Jing; Yan, Hua; Zhao, Kebin; Wang, Chuduan; Wang, Lixian; Zhang, Longchao

    2012-01-01

    Pork quality is an economically important trait and one of the main selection criteria for breeding in the swine industry. In this genome-wide association study (GWAS), 455 pigs from a porcine Large White × Minzhu intercross population were genotyped using the Illumina PorcineSNP60K Beadchip, and phenotyped for intramuscular fat content (IMF), marbling, moisture, color L*, color a*, color b* and color score in the longissimus muscle (LM). Association tests between each trait and the SNPs were performed via the Genome Wide Rapid Association using the Mixed Model and Regression-Genomic Control (GRAMMAR-GC) approach. From the Ensembl porcine database, SNP annotation was implemented using Sus scrofa Build 9. A total of 45 SNPs showed significant association with one or multiple meat quality traits. Of the 45 SNPs, 36 were located on SSC12. These significantly associated SNPs aligned to or were in close approximation to previously reported quantitative trait loci (QTL) and some were located within introns of previously reported candidate genes. Two haplotype blocks ASGA0100525-ASGA0055225-ALGA0067099-MARC0004712-DIAS0000861, and ASGA0085522-H3GA0056170 were detected in the significant region. The first block contained the genes MYH1, MYH2 and MYH4. A SNP (ASGA0094812) within an intron of the USP43 gene was significantly associated with five meat quality traits. The present results effectively narrowed down the associated regions compared to previous QTL studies and revealed haplotypes and candidate genes on SSC12 for meat quality traits in pigs. PMID:22532790

  5. Host Plant-Associated Population Variation in the Carob Moth Ectomyelois ceratoniae in Iran: A Geometric Morphometric Analysis Suggests a Nutritional Basis.

    PubMed Central

    Mozaffarian, Fariba; Sarafrazi, Alimorad; Ganbalani, Gadir Nouri

    2007-01-01

    The carob moth, Ectomyelois ceratoniae (Zeller, 1839) (Lepidoptera: Pyralidae), is the most important pest of pomegranate in Iran. As it has been rarely recorded on other host plants, control methods have mostly been focused on its populations on pomegranate. In this study, shapes and sizes of wings were compared in populations on 4 host plants (pomegranate, fig, pistachio and walnut) using a landmark-based geometric morphometric method, and analysis of partial warp scores and centroid sizes. The results showed significantly smaller wing size in populations on pomegranate and a significant host plant-associated shape difference among populations as a consequence of allometric growth. This suggests that the wing size and shape differences among test populations may not have a genetic basis and could happen because of differences in the nutritional content of host plants. The results of the analysis suggest that the female carob moth lays her eggs on host plants that provide suitable conditions for hatching. The larger size of moths on hosts other than pomegranate showed that some host plants such as fig, pistachio and walnut can provide for increased stored nutritional reserves by larvae that may result in more successful over-wintering and higher fecundity in adults. This suggests that in spite of the more extensive activity of carob moth on pomegranate in Iran, populations on other host plants can have an important effect on expanding pest population sizes in following years which should be considered in control methods. PMID:20337550

  6. Pilot study for family-based association analysis of schizophrenia in a Korean population: Analysis for candidate genes positionally on chromosome 18q21.

    PubMed

    Cho, Min Jung; Lee, Byung Dae; Kim, Choongrak

    2015-09-01

    Schizophrenia is the most devastating mental illness that causes severe deterioration in social and occupational functioning. This is a pilot study for family-based association analysis of schizophrenia in a Korean population to search candidate genes functionally relevant and positionally on chromosome 18. We have recruited 27 probands (with psychosis) with their parents and siblings whenever possible. We analyzed 20 SNPs (Single Nucleotide Polymorphism) of seven neuronal genes in chromosome 18 for DNA samples that was checked for the data quality and genotype error. For testing of association, we performed family-based association tests analyses with each individual SNP, using the phenotype of psychosis. And then, we performed family-based association tests haplotype analyses with each individual SNP, using the phenotype of psychosis. Finally, we performed linkage disequilibrium analyses for the phenotype of schizophrenia. We found one significant SNPs of one neuronal gene in chromosome 18 (P value < 0.05) for the qualitative phenotype of psychosis (rs1893490:MAPK4). We also found significant haplotypes of four SNPs in mitogen-activated protein kinase 4 (MAPK4) gene of chromosome 18 (P value < 0.1) for the phenotype of psychosis (rs1893490-rs3892158-rs3752088-rs3794899). Two SNPS within the MAPK4 gene (rs3794899, rs3794901), plus SNPs within the malic enzyme 2 (rs685533, rs12277), and SMAD4 genes (rs8096092, rs2298617) were in strong linkage disequilibrium with each other (D' > 0.60). The present findings provide convergent evidence (fine mapping of a chromosomal locus 18q21 associated with schizophrenia) suggesting that a specific MAPK4 could be a candidate gene for causing a spectrum of schizophrenia phenotype. © 2014 Wiley Publishing Asia Pty Ltd.

  7. Association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke in the Chinese population: a meta-analysis.

    PubMed

    Zhu, Xiao-Yan; Hou, Rong-Yao; Pan, Xu-Dong; Wang, Yu-Chun; Zhang, Zheng-Shou; Guo, Rui-You

    2015-01-01

    The association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke (IS) has been extensively studied; however, the results from genetic association studies have been inconsistent even in the Chinese population. As far as we know, there was no previous meta-analysis concerning this association in the Chinese population. Therefore, the aim of our meta-analysis was to further evaluate the association in the Chinese population. We collected all of the relevant studies from Pubmed, OVID, Embase, Chinese Wan Fang database, CNKI, Chongqing VIP database and CBM up to August 2014. The available data was analyzed by Stata (version 12.0). We used odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to present the strength of the association. Heterogeneity was evaluated by the Q-test and I(2) statistic. Different genetic models, subgroup analysis, publication bias and sensitivity analysis were used to improve the comprehensive understanding. The results showed a significant association between the MTHFR gene C677T polymorphism and IS in six genetic models (additive model: OR = 1.34, 95%CI: 1.17 ∼ 1.54, p < 0.001; dominant model: OR = 1.44, 95% CI:1.26 ∼ 1.64, p < 0.001; recessive model: OR = 1.45, 95% CI: 1.15 ∼ 1.83, p = 0.001; heterozygote model: OR = 1.35, 95% CI: 1.18 ∼ 1.55, p < 0.001; homozygote model: OR = 1.80, 95% CI: 1.34 ∼ 2.41, p < 0.001; and allelic model: OR = 1.34, 95% CI: 1.17 ∼ 1.53, p < 0.001) based on the overall population, as well as subgroup analysis. In addition, the similar results were obtained in the sensitivity analysis based on studies with the high quality. This meta-analysis presented a significant association between the MTHFR gene C677T polymorphism and IS, the T allele might be a risk factor for IS in the Chinese population.

  8. Gene-wide association study between the methylenetetrahydrofolate reductase gene (MTHFR) and schizophrenia in the Japanese population, with an updated meta-analysis on currently available data.

    PubMed

    Yoshimi, Akira; Aleksic, Branko; Kawamura, Yukiko; Takahashi, Nagahide; Yamada, Shinnosuke; Usui, Hinako; Saito, Shinichi; Ito, Yoshihito; Iwata, Nakao; Inada, Toshiya; Noda, Yukihiro; Yamada, Kiyofumi; Ozaki, Norio

    2010-12-01

    Methylenetetrahydrofolate reductase (MTHFR) is a critical molecule for single-carbon transfer reactions. Recent evidence suggests that polymorphisms of MTHFR are related to neural tube deficits and the pathogenesis of schizophrenia. While several studies have demonstrated associations between the gene encoding the MTHFR (MTHFR) polymorphisms and schizophrenia, these studies lack consistency. Therefore, we conducted a gene-wide association study (patients with schizophrenia = 696, control subjects = 747) and performed imputation analysis. Additionally, we performed meta-analysis on currently available data from 18 studies for two common functional polymorphisms (rs1801131 and rs1801133). There were no significant associations with schizophrenia in the single marker analysis for the seven tagging SNPs of MTHFR. In the haplotypic analysis, a nominally significant association was observed between the haplotypes, which included four SNPs (rs1801133, rs17421511, rs17037396, and rs9651118) and the schizophrenic patients. Additionally, the imputation analysis demonstrated there were several associated markers on the MTHFR chromosomal region. However, confirmatory analyses of three tagging SNPs (rs1801133, rs17037396, and rs9651118) and the top SNP (rs17421511) for the imputation results (patients with schizophrenia = 797, control subjects = 1025) failed to replicate the haplotypic analysis and the imputation results. These findings suggest that MTHFR polymorphisms are unlikely to be related to the development of schizophrenia in the Japanese population. However, since our meta-analysis results demonstrated strong support for association of rs1801133 with schizophrenia, further replication studies based on a gene-wide approach need to be considered.

  9. Rank-based genome-wide analysis reveals the association of Ryanodine receptor-2 gene variants with childhood asthma among human populations

    PubMed Central

    2013-01-01

    Background The standard approach to determine unique or shared genetic factors across populations is to identify risk alleles in one population and investigate replication in others. However, since populations differ in DNA sequence information, allele frequencies, effect sizes, and linkage disequilibrium patterns, SNP association using a uniform stringent threshold on p values may not be reproducible across populations. Here, we developed rank-based methods to investigate shared or population-specific loci and pathways for childhood asthma across individuals of diverse ancestry. We performed genome-wide association studies on 859,790 SNPs genotyped in 527 affected offspring trios of European, African, and Hispanic ancestry using publically available asthma database in the Genotypes and Phenotypes database. Results Rank-based analyses showed that there are shared genetic factors for asthma across populations, more at the gene and pathway levels than at the SNP level. Although the top 1,000 SNPs were not shared, 11 genes (RYR2, PDE4D, CSMD1, CDH13, ROBO2, RBFOX1, PTPRD, NPAS3, PDE1C, SEMA5A, and CTNNA2) mapped by these SNPs were shared across populations. Ryanodine receptor 2 (RYR2, a statin response-related gene) showed the strongest association in European (p value = 2.55 × 10−7) and was replicated in African (2.57 × 10−4) and Hispanic (1.18 × 10−3) Americans. Imputation analyses based on the 1000 Genomes Project uncovered additional RYR2 variants associated with asthma. Network and functional ontology analyses revealed that RYR2 is an integral part of dermatological or allergic disorder biological networks, specifically in the functional classes involving inflammatory, eosinophilic, and respiratory diseases. Conclusion Our rank-based genome-wide analysis revealed for the first time an association of RYR2 variants with asthma and replicated previously discovered PDE4D asthma gene across human populations. The replication of top

  10. Association between chronic osteomyelitis and deep-vein thrombosis. Analysis of a nationwide population-based registry.

    PubMed

    Lin, T-Y; Chen, Y-G; Huang, W-Y; Lin, C-L; Peng, C-L; Sung, F-C; Kao, C-H

    2014-09-02

    Studies on the association between chronic osteomyelitis and deep vein thrombosis (DVT) and pulmonary thromboembolism (PE) are scarce. The aim of this study was to analyse a nationwide population-based database for association between DVT or PE after a diagnosis of chronic osteomyelitis. This nationwide population-based cohort study was based on data obtained from the Taiwan National Health Insurance Database from 1998 to 2008, with a follow-up period extending to the end of 2010. We identified patients with chronic osteomyelitis using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. The patients with chronic osteomyelitis and comparison controls were selected by 1:1 matching on a propensity score. The propensity score was calculated by a logistic regression to estimate the probability of the treatment assignment given the baseline variables including age, sex, and Charlson comorbidity index score. We analysed the risks of DVT and PE by using Cox proportional hazards regression models, including sex, age, and comorbidities. In total, 24,335 chronic osteomyelitis patients and 24,335 controls were enrolled in the study. The risk of developing DVT was 2.49-fold in patients with chronic osteomyelitis compared with the comparison cohort, after adjusting for age, sex, and comorbidities. The multiplicative increased risks of DVT were also significant in patients with chronic osteomyelitis with any comorbidity. In conclusion, physicians should consider chronic osteomyelitis in their evaluation of risk factors for DVT.

  11. Genetic association between IL-27 rs153109 polymorphism and cancer risk in Chinese population: a meta-analysis.

    PubMed

    Xu, Xiu-Peng; Hua, Ling-Yang; Chao, Hong-Lu; Chen, Zheng-Xin; Wang, Xie-Feng; Ji, Jing; Liu, Ning

    2017-08-01

    IL-27 plays an important role in anti-cancer activity. The -964A/G polymorphism in IL-27 gene has been implicated in susceptibility to cancer, but the results were conflicting. The aim of this study was to assess the association between this polymorphism and cancer risk. Pubmed and Wanfang database were searched for all publications concerning IL-27 -964A/G polymorphism and cancer risk. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of association. Statistical analysis was performed using Stata 11.0 software. A total of eight case-control studies including 2044 cancer cases and 2197 controls were identified. Overall, significant association between IL-27 -964A/G polymorphism and cancer risk was observed (GG versus AA: OR = 1.26, 95% CI = 1.03-1.52; GG versus AG + AA: OR = 1.20, 95% CI = 1.00-1.44). In subgroup analysis based on cancer type, significant association was found in colorectal cancer (GG versus AA: OR = 1.55, 95% CI = 1.07-2.27; AG versus AA: OR = 1.31, 95% CI = 1.02-1.67). The current meta-analysis suggests that IL-27 -964A/G polymorphism might enhance cancer risk. However, large-scale and well-designed studies are still needed to confirm the result of our meta-analysis. The association of IL-27 polymorphism with colorectal cancer may provide insight for future therapies.

  12. Association of Sjögrens Syndrome in Patients with Chronic Hepatitis Virus Infection: A Population-Based Analysis

    PubMed Central

    Yeh, Chih-Ching; Wang, Wen-Chang; Wu, Chien-Sheng; Sung, Fung-Chang; Su, Chien-Tien; Shieh, Ying-Hua; Chang, Shih-Ni; Su, Fu-Hsiung

    2016-01-01

    Objective The association between Sjögren’s syndrome (SS) and chronic hepatitis virus infection is inconclusive. Hepatitis B (HBV) and hepatitis C virus (HCV) infections are highly prevalent in Taiwan. We used a population-based case-control study to evaluate the associations between SS and HBV and HCV infections. Materials and Methods We identified 9,629 SS patients without other concomitant autoimmune diseases and 38,516 sex- and age-matched controls without SS from the Taiwan National Health Insurance claims data between 2000 and 2011. We utilized multivariate logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between SS and HBV and HCV infections. Sex- and age-specific (<55 and ≥55 years) risks of SS were evaluated. Results The risk of SS was higher in patients with HCV than in those without chronic viral hepatitis (OR = 2.49, 95% CI = 2.16–2.86). Conversely, HBV infection was not associated with SS (OR = 1.10, 95% CI = 0.98–1.24). Younger HCV patients were at a higher risk for SS (<55 years: OR = 3.37, 95% CI = 2.62–4.35; ≥55 years: OR = 2.20, 95% CI = 1.84–2.62). Men with HCV were at a greater risk for SS (women: OR = 2.26, 95% CI = 1.94–2.63; men: OR = 4.22, 95% CI = 2.90–6.16). Only men with chronic HBV exhibited a higher risk of SS (OR = 1.61, 95% CI = 1.21–2.14). Conclusion HCV infection was associated with SS; however, HBV only associated with SS in men. PMID:27560377

  13. Association between triglycerides and cardiovascular events in primary populations: a meta-regression analysis and synthesis of evidence.

    PubMed

    Stauffer, Melissa E; Weisenfluh, Lauren; Morrison, Alan

    2013-01-01

    Triglyceride levels were found to be independently predictive of the development of primary coronary heart disease in epidemiologic studies. The objective of this study was to determine whether triglyceride levels were predictive of cardiovascular events in randomized controlled trials (RCTs) of lipid-modifying drugs. We performed a systematic review and meta-regression analysis of 40 RCTs of lipid-modifying drugs with cardiovascular events as an outcome. The log of the rate ratio of cardiovascular events (eg, coronary death or myocardial infarction) was plotted against the proportional difference between treatment and control groups in triglyceride and other lipid levels (high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C], and total cholesterol) for all trials and for trials of primary and secondary prevention populations. Linear regression was used to determine the statistical significance of the relationship between lipid values and cardiovascular events. The proportional difference in triglyceride levels was predictive of cardiovascular events in all trials (P=0.005 for the slope of the regression line; N=40) and in primary prevention trials (P=0.010; N=11), but not in secondary prevention trials (P=0.114; N=25). The proportional difference in HDL-C was not predictive of cardiovascular events in all trials (P=0.822; N=40), or in trials of primary (P=0.223; N=11) or secondary (P=0.487; N=25) prevention. LDL-C levels were predictive of cardiovascular events in both primary (P=0.002; N=11) and secondary (P<0.001; N=25) populations. Changes in triglyceride levels were predictive of cardiovascular events in RCTs. This relationship was significant in primary prevention populations but not in secondary prevention populations.

  14. Association between triglycerides and cardiovascular events in primary populations: a meta-regression analysis and synthesis of evidence

    PubMed Central

    Stauffer, Melissa E; Weisenfluh, Lauren; Morrison, Alan

    2013-01-01

    Background Triglyceride levels were found to be independently predictive of the development of primary coronary heart disease in epidemiologic studies. The objective of this study was to determine whether triglyceride levels were predictive of cardiovascular events in randomized controlled trials (RCTs) of lipid-modifying drugs. Methods We performed a systematic review and meta-regression analysis of 40 RCTs of lipid-modifying drugs with cardiovascular events as an outcome. The log of the rate ratio of cardiovascular events (eg, coronary death or myocardial infarction) was plotted against the proportional difference between treatment and control groups in triglyceride and other lipid levels (high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C], and total cholesterol) for all trials and for trials of primary and secondary prevention populations. Linear regression was used to determine the statistical significance of the relationship between lipid values and cardiovascular events. Results The proportional difference in triglyceride levels was predictive of cardiovascular events in all trials (P=0.005 for the slope of the regression line; N=40) and in primary prevention trials (P=0.010; N=11), but not in secondary prevention trials (P=0.114; N=25). The proportional difference in HDL-C was not predictive of cardiovascular events in all trials (P=0.822; N=40), or in trials of primary (P=0.223; N=11) or secondary (P=0.487; N=25) prevention. LDL-C levels were predictive of cardiovascular events in both primary (P=0.002; N=11) and secondary (P<0.001; N=25) populations. Conclusions Changes in triglyceride levels were predictive of cardiovascular events in RCTs. This relationship was significant in primary prevention populations but not in secondary prevention populations. PMID:24204156

  15. Gene-Based Genome-Wide Association Analysis in European and Asian Populations Identified Novel Genes for Rheumatoid Arthritis

    PubMed Central

    Zhu, Hong; Xia, Wei; Mo, Xing-Bo; Lin, Xiang; Qiu, Ying-Hua; Yi, Neng-Jun; Zhang, Yong-Hong; Deng, Fei-Yan; Lei, Shu-Feng

    2016-01-01

    Objective Rheumatoid arthritis (RA) is a complex autoimmune disease. Using a gene-based association research strategy, the present study aims to detect unknown susceptibility to RA and to address the ethnic differences in genetic susceptibility to RA between European and Asian populations. Methods Gene-based association analyses were performed with KGG 2.5 by using publicly available large RA datasets (14,361 RA cases and 43,923 controls of European subjects, 4,873 RA cases and 17,642 controls of Asian Subjects). For the newly identified RA-associated genes, gene set enrichment analyses and protein-protein interactions analyses were carried out with DAVID and STRING version 10.0, respectively. Differential expression verification was conducted using 4 GEO datasets. The expression levels of three selected ‘highly verified’ genes were measured by ELISA among our in-house RA cases and controls. Results A total of 221 RA-associated genes were newly identified by gene-based association study, including 71‘overlapped’, 76 ‘European-specific’ and 74 ‘Asian-specific’ genes. Among them, 105 genes had significant differential expressions between RA patients and health controls at least in one dataset, especially for 20 genes including 11 ‘overlapped’ (ABCF1, FLOT1, HLA-F, IER3, TUBB, ZKSCAN4, BTN3A3, HSP90AB1, CUTA, BRD2, HLA-DMA), 5 ‘European-specific’ (PHTF1, RPS18, BAK1, TNFRSF14, SUOX) and 4 ‘Asian-specific’ (RNASET2, HFE, BTN2A2, MAPK13) genes whose differential expressions were significant at least in three datasets. The protein expressions of two selected genes FLOT1 (P value = 1.70E-02) and HLA-DMA (P value = 4.70E-02) in plasma were significantly different in our in-house samples. Conclusion Our study identified 221 novel RA-associated genes and especially highlighted the importance of 20 candidate genes on RA. The results addressed ethnic genetic background differences for RA susceptibility between European and Asian populations and

  16. Lactic acid bacteria associated with vacuum-packed cooked meat product spoilage: population analysis by rDNA-based methods.

    PubMed

    Chenoll, E; Macián, M C; Elizaquível, P; Aznar, R

    2007-02-01

    To determine the lactic acid bacteria (LAB) implicated in bloating spoilage of vacuum-packed and refrigerated meat products. A total of 18 samples corresponding to four types of meat products, with and without spoilage symptoms, were studied. In all, 387 colonies growing on de Man, Rogosa and Sharpe, yeast glucose lactose peptone and trypticase soy yeast extract plates were identified by internal spacer region (ISR), ISR-restriction fragment length polymorphism and rapid amplified ribosomal DNA restriction analysis profiles as Lactobacillus (37%), Leuconostoc (43%), Carnobacterium (11%), Enterococcus (4%) and Lactococcus (2%). Leuconostoc mesenteroides dominated the microbial population of spoiled products and was always present at the moment bloating occurred. Lactobacillus sakei, Lactobacillus plantarum and Lactobacillus curvatus were found in decreasing order of abundance. The analysis of two meat products, 'morcilla' and 'fiambre de magro adobado' obtained from production lines revealed a common succession pattern in LAB populations in both products and showed that Leuc. mesenteroides became the main species during storage, despite being below the detection level of culture methods after packing. Our results pointed to Leuc. mesenteroides as the main species responsible for bloating spoilage in vacuum-packed meat products. Prevention of bloating spoilage in vacuum-packed cooked meat products requires the sensitive detection of Leuc. mesenteroides (i.e. by PCR).

  17. The G894T polymorphism on endothelial nitric oxide synthase gene is associated with increased coronary heart disease among Asia population: evidence from a Meta analysis.

    PubMed

    Zhang, Kui; Bai, Peng; Shi, Shaoqing; Zhou, Bin; Wang, Yanyun; Song, Yaping; Rao, Li; Zhang, Lin

    2012-08-01

    Growing studies have revealed the underlying association between eNOS 894G/T (rs1799983) polymorphism and coronary heart disease (CHD) among Asia population. Results from these studies remained conflicting. We conducted this meta-analysis to estimate the overall CHD risk of eNOS 894G/T polymorphism regarding Asia population. Up to October 2011, databases including PubMed, Embase and CNKI (China National Knowledge Infrastructure) were searched to access the relevant genetic association studies. Summary odds ratios and corresponding 95% confidence intervals (CIs) for eNOS 894G/T polymorphism and CHD risk were estimated using fixed or random-effects models when appropriate. 18 case-control studies with 2,994 cases and 3,130 controls were available for this study, including 13 studies of East-Asia descendents, 5 studies of Non East-Asian descendents. The mean T allele frequency was 0.111 in the East-Asia population and 0.147 in the Non East-Asia population, respectively. The summary OR for CHD associated with the T allele was 1.52 (95% confidence intervals (95%CI), 1.37-1.69) by random effects model. Similarly, significantly increased risks were observed in the East-Asia population (OR=1.54; 95%CI=1.35-1.76) and in the Non East-Asia population (OR=1.48; 95%CI=1.24-1.77), respectively. This meta-analysis indicated that eNOS 894G/T polymorphism may play an important role in CHD development among Asia population. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Lack of Association Between MTHFR, MTR, MTRR, and TCN2 Genes and Nonsyndromic CL±P in a Chinese Population: Case-Control Study and Meta-Analysis.

    PubMed

    Jiang, Chanyuan; Yin, Ningbei; Zhao, Zhenmin; Wu, Di; Wang, Yongqian; Li, Haidong; Song, Tao

    2015-09-01

    Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common congenital deformity, often associated with folate deficiency. The genes MTHFR, MTR, MTRR, and TCN2 play key roles in folate metabolism. The risk of NSCLP associated with particular variants in the folic acid pathway differs among ethnic groups. The goal of this study was to explore whether genetic variations in these four genes, as well as gene-gene interactions, are associated with NSCLP. We investigated 7 tagSNPs for MTHFR, 18 tagSNPs for MTR, 15 tagSNPs for MTRR, and 7 tagSNPs for TCN2 selected from HapMap data in a Chinese population. These single nucleotide polymorphisms (SNPs) were examined for associations with NSCLP in 204 patients and 226 controls. We then performed a meta-analysis of association between rs1801133 and NSCLP. There was a significant difference in the allele frequency and haplotype analysis of rs4077829 and rs10802565 in MTR between the NSCLP and control groups but not a significant difference after correction with 10,000 times permutations. The allele frequency, haplotype analysis, and gene-gene interactions of other SNPs did not show a significant difference. The meta-analysis results showed that no significant differences were found for allele comparison, heterozygote comparison, homozygote comparison, dominant model comparison, or recessive model comparison. The alterations of folate metabolism related to these polymorphisms are not involved in NSCLP in the Chinese population.

  19. Association of lncRNA H19 rs217727 polymorphism and cancer risk in the Chinese population: a meta-analysis

    PubMed Central

    Shen, Na; Peng, Jing; Wang, Chunyu; Zhu, Yaowu; Wang, Xiong

    2016-01-01

    Reports on the relationship between the lncRNA H19 rs217727 polymorphism and the risk of cancer in the Chinese population have been inconsistent. Therefore, we performed a meta-analysis to evaluate this association, by searching the Embase, PubMed, Web of Science, Wanfang, and CNKI databases. Four case-control studies with 3,157 cases and 3,564 controls were selected for this meta-analysis. The odds ratios with 95% confidence intervals were examined using the random effect model. Allelic (A vs. G), dominant (AA + GA vs. GG), recessive (AA vs. GA + GG), and additive (AA vs. GG) genetic models were used to determine the association. Overall, no significant association was observed between the rs217727 polymorphism and cancer susceptibility in any of the four genetic models. Sensitivity analysis revealed that the results were stable in the allelic and dominant genetic models, but those from the recessive and additive models were unstable, which should be treated with caution. Our meta-analysis suggests that the lncRNA H19 rs217727 polymorphism might not be associated with overall cancer risk. However, well-designed, large-scale studies with different ethnic populations need to be conducted in the future to elucidate the potential association. PMID:27486980

  20. Association between the V Leiden G1691A mutation and sudden sensorineural hearing loss in Italian population: a meta-analysis.

    PubMed

    Shu, Jingcheng; Si, Yongfeng; Yin, Shihua; He, Meirong

    2016-09-01

    Epidemiological studies have reported inconsistent findings on the association between the V Leiden G1691A mutation and sudden sensorineural hearing loss (SSNHL) in Italian population. The aim of this meta-analysis was to clarify this association. PubMed, Embase, and the China National Knowledge Infrastructure (CNKI) were searched up to April 1, 2015. We used STATA12.0 to calculate summary odds ratios (ORs) with 95 % confidence intervals (CIs). Four studies including 958 patients were identified. Pooled data showed no significant association between V Leiden G1691A mutation and risk of SSNHL in Italian population: A vs. G (OR = 1.660, 95 % CI 0.428-6.446, P OR = 0.464) and AG vs. GG (OR = 1.680, 95 % CI 0.422-6.688, P OR = 0.462). The present meta-analysis suggests that V Leiden G1691A mutation is not significantly associated with increased risk of SSNHL disease in Italian population. Further large and well-designed studies are needed to confirm this association.

  1. Exploring causal associations of alcohol with cardiovascular and metabolic risk factors in a Chinese population using Mendelian randomization analysis

    PubMed Central

    Taylor, Amy E.; Lu, Feng; Carslake, David; Hu, Zhibin; Qian, Yun; Liu, Sijun; Chen, Jiaping; Shen, Hongbing; Smith, George Davey

    2015-01-01

    Observational studies suggest that moderate alcohol consumption may be protective for cardiovascular disease, but results may be biased by confounding and reverse causality. Mendelian randomization, which uses genetic variants as proxies for exposures, can minimise these biases and therefore strengthen causal inference. Using a genetic variant in the ALDH2 gene associated with alcohol consumption, rs671, we performed a Mendelian randomization analysis in 1,712 diabetes cases and 2,076 controls from Nantong, China. Analyses were performed using linear and logistic regression, stratified by sex and diabetes status. The A allele of rs671 was strongly associated with reduced odds of being an alcohol drinker in all groups, but prevalence of alcohol consumption amongst females was very low. The A allele was associated with reduced systolic and diastolic blood pressure and decreased total and HDL cholesterol in males. The A allele was also associated with decreased triglyceride levels, but only robustly in diabetic males. There was no strong evidence for associations between rs671 and any outcomes in females. Our results suggest that associations of alcohol consumption with blood pressure and HDL-cholesterol are causal. Alcohol also appeared to have adverse effects on triglyceride levels, although this may be restricted to diabetics. PMID:26364564

  2. Exploring causal associations of alcohol with cardiovascular and metabolic risk factors in a Chinese population using Mendelian randomization analysis.

    PubMed

    Taylor, Amy E; Lu, Feng; Carslake, David; Hu, Zhibin; Qian, Yun; Liu, Sijun; Chen, Jiaping; Shen, Hongbing; Smith, George Davey

    2015-09-14

    Observational studies suggest that moderate alcohol consumption may be protective for cardiovascular disease, but results may be biased by confounding and reverse causality. Mendelian randomization, which uses genetic variants as proxies for exposures, can minimise these biases and therefore strengthen causal inference. Using a genetic variant in the ALDH2 gene associated with alcohol consumption, rs671, we performed a Mendelian randomization analysis in 1,712 diabetes cases and 2,076 controls from Nantong, China. Analyses were performed using linear and logistic regression, stratified by sex and diabetes status. The A allele of rs671 was strongly associated with reduced odds of being an alcohol drinker in all groups, but prevalence of alcohol consumption amongst females was very low. The A allele was associated with reduced systolic and diastolic blood pressure and decreased total and HDL cholesterol in males. The A allele was also associated with decreased triglyceride levels, but only robustly in diabetic males. There was no strong evidence for associations between rs671 and any outcomes in females. Our results suggest that associations of alcohol consumption with blood pressure and HDL-cholesterol are causal. Alcohol also appeared to have adverse effects on triglyceride levels, although this may be restricted to diabetics.

  3. Confirmatory factor analysis of the Adult Asperger Assessment: the association of symptom domains within a clinical population.

    PubMed

    Kuenssberg, Renate; McKenzie, Karen

    2011-01-01

    Autism Spectrum Disorder (ASD) is a behaviourally defined disorder characterised by impairments in three domains of social interaction, communication, and repetitive, stereotyped behaviours and activities. Proposed changes to diagnostic criteria suggest that the diagnostic triad may no longer fit as the best way to conceptualise ASD, and that social and communication impairments should be considered as a single domain. The aim of this study was to examine the structure of symptom domains within the Adult Asperger Assessment (AAA; Baron-Cohen, Wheelwright, Robinson, & Woodbury-Smith, 2005), a diagnostic tool for high functioning adults. As theoretical models already exist, confirmatory factor analysis was used to examine data from a clinical population of adults (n = 153) diagnosed with Asperger Syndrome (AS) and High Functioning Autism (HFA). Confirmatory factor analysis was used to fit different models based on the structure proposed by the authors of the AAA, the traditional triad and the newly proposed diagnostic dyad. Analysis suggested that none of the tested models were a good fit on the AAA dataset. However, it did highlight very high correlations between social and communication factors (r > 0.9) within unmodified models. The results of the analysis provide tentative support for the move towards considering ASD as a dyad of 'social-communication' impairments and repetitive/restricted interests behaviours and activities, rather than the traditional triad.

  4. The association analysis of hOGG1 genetic variants and gastric cancer risk in a Chinese population

    PubMed Central

    Ma, Gaoxiang; Ge, Yuqiu; Zhang, Qiang; Chu, Haiyan; Tong, Na; Wang, Meilin; Qiu, Jinrong; Zhang, Zhengdong

    2016-01-01

    Human 8-oxoguanine DNA glycosylase (hOGG1) is known to play an important role in the prevention of carcinogenesis, including gastric cancer (GC). We performed a case-control study to investigate whether single nucleotide polymorphisms (SNPs) of hOGG1 are associated with GC risk in a Chinese population. Two potential functional tagSNPs (rs159153 and rs1052133) and a previously reported risk SNP (rs125701) were genotyped in 1,275 GC patients and 1,436 controls. We found that SNP rs125701 G > A was significantly associated with the increased GC risk [adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.05-1.79 in additive model]. Besides, the functional studies demonstrated that the minor A allele of rs125701 significantly reduced the transcriptional activity of hOGG1 promoter and enhanced the methylation level of CpG site of cg15357639. In conclusion, our results suggested that the SNP rs125701 in hOGG1 promoter was associated with the elevated GC risk, which could act as a new potential biomarker for GC susceptibility. Further functional verification of rs125701 in GC pathogenesis is warranted. PMID:27603140

  5. Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans

    PubMed Central

    Taravella, Angela M.; Bustamante, Carlos D.; Sikora, Martin

    2017-01-01

    The human DARC (Duffy antigen receptor for chemokines) gene encodes a membrane-bound chemokine receptor crucial for the infection of red blood cells by Plasmodium vivax, a major causative agent of malaria. Of the three major allelic classes segregating in human populations, the FY*O allele has been shown to protect against P. vivax infection and is at near fixation in sub-Saharan Africa, while FY*B and FY*A are common in Europe and Asia, respectively. Due to the combination of strong geographic differentiation and association with malaria resistance, DARC is considered a canonical example of positive selection in humans. Despite this, details of the timing and mode of selection at DARC remain poorly understood. Here, we use sequencing data from over 1,000 individuals in twenty-one human populations, as well as ancient human genomes, to perform a fine-scale investigation of the evolutionary history of DARC. We estimate the time to most recent common ancestor (TMRCA) of the most common FY*O haplotype to be 42 kya (95% CI: 34–49 kya). We infer the FY*O null mutation swept to fixation in Africa from standing variation with very low initial frequency (0.1%) and a selection coefficient of 0.043 (95% CI:0.011–0.18), which is among the strongest estimated in the human genome. We estimate the TMRCA of the FY*A mutation in non-Africans to be 57 kya (95% CI: 48–65 kya) and infer that, prior to the sweep of FY*O, all three alleles were segregating in Africa, as highly diverged populations from Asia and ≠Khomani San hunter-gatherers share the same FY*A haplotypes. We test multiple models of admixture that may account for this observation and reject recent Asian or European admixture as the cause. PMID:28282382

  6. ERAP1 variants are associated with ankylosing spondylitis in East Asian population: a new Chinese case-control study and meta-analysis of published series.

    PubMed

    Chen, C; Zhang, X

    2015-06-01

    Endoplasmic reticulum aminopeptidase 1 (ERAP1) has been confirmed to be associated with ankylosing spondylitis (AS) in Caucasian. However, whether they are associated with AS in East Asian population remains unidentified. We investigated this relationship by a new Chinese case-control study and a meta-analysis of published series. 368 cases and 460 controls were recruited in the Chinese case-control study. Genotyping was completed using the chip-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Allelic associations were analysed using contingency tables. In the meta-analysis, up to 2748 cases and 2774 controls from seven different studies and the new Chinese study were combined using Review Manager software version 5.1.1. Mantel-Haenszel or Inverse Variance test was used to calculate fixed or random-effects pooled ORs. In the new Chinese study, strong association with AS was observed for marker rs10050860, rs27434 and rs1065407 at P value of <0.001. Moderate association was observed for rs30187 at P value of <0.01, while no association was observed for rs27044 (P = 0.37) and rs2287987 (P = 0.23). The meta-analysis showed that rs27037 and rs30187 were strongly associated with AS (P < 0.00001). Significant association was also observed for rs27434 (P = 0.001). No association was shown for rs27044 (P = 0.70). We concluded that ERAP1 variants are associated with AS in East Asian population, indicating a common pathogenic mechanism for AS in East Asians and Caucasians.

  7. Association analysis of the IL-1 gene cluster polymorphisms with aggressive and chronic periodontitis in the Algerian population.

    PubMed

    Boukortt, Kawther Nourelhouda; Saidi-Ouahrani, Nadjia; Boukerzaza, Boubaker; Ouhaibi-Djellouli, Hadjira; Hachmaoui, Khalida; Benaissa, Fatima Zohra; Taleb, Leila; Drabla-Ouahrani, Hayet; Deba, Tahria; Ouledhamou, Sid Ahmed; Mehtar, Nadhera; Boudjema, Abdellah

    2015-10-01

    There is strong evidence that genetic as well as environmental factors affect the development of periodontitis. Various studies suggest that genetic polymorphisms of the interleukin-1 (IL-1) genes are associated with an increased risk of developing the pathogenesis. The aim of the present study was to investigate the possible relationship between two polymorphisms of IL-1 gene cluster IL-1B (C+3954T) (rs1143634) and IL-1A (C-889T) (rs1800587) SNPs and the aggressive and chronic periodontitis risk in a case control study in Algerian population. 279 subjects were recruited and received a periodontal examination: 128 healthy controls and 151 cases. From cases, 91 patients were having a chronic disease whereas 60 subjects with aggressive form. All these subjects were genotyped for IL-1A (C-889T) and IL-1B (C+3954T) polymorphisms using TaqMan real time PCR technology. Frequencies of IL-1 alleles, genotypes and the haplotypes were also examined. Significant differences were found in the carriage rate of both minor alleles of the IL-1A (C-889T) and IL-1B (C+3954T) polymorphisms of aggressive periodontitis cases compared with healthy controls (OR [95%CI]=1.61 [1.03-2.49], p=0.03), (OR [95%CI]=1.69 [1.09-2.63], p=0.01), respectively. The result did not reach significance with the chronic form. The studied polymorphisms of the IL-1 genes appear to be associated with susceptibility to aggressive periodontitis (AgP) in the Algerian population. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Association between C677T polymorphism of MTHFR gene and risk of amyotrophic lateral sclerosis: Polish population study and a meta-analysis.

    PubMed

    Żur-Wyrozumska, Kamila; Pera, Joanna; Dziubek, Anna; Sado, Małgorzata; Golenia, Aleksandra; Słowik, Agnieszka; Dziedzic, Tomasz

    Genetic factors play a role in pathogenesis of amyotrophic lateral sclerosis (ALS). A few studies demonstrated that the TT genotype of C677T polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene can increase the risk of sporadic ALS. The aim of our study was to determine the relationship between C677T polymorphism of MTHFR gene and the risk of sporadic ALS in Polish population and to perform the meta-analysis assessing the significance this polymorphism for the risk of ALS in Caucasian population. We included 251 patients with ALS and 500 control subjects recruited from Polish population and performed the meta-analysis of published data from Caucasian population. MTHFR C677T polymorphism was genotyped using a TaqMan assay and 7900HT Fast real Time PCR System. The frequency of genotypes did not differ significantly between Polish ALS patients and control subjects (CC: 45.0 vs 45.8%, CT: 48.2 vs 45.0%, TT: 6.8 vs 9.2%, P=0.46). The meta-analysis including 863 ALS patients and 1362 controls revealed that TT genotype increases the risk of sporadic ALS in Caucasian population. Although we did not find the association between C677T polymorphism of MTHRF gene and risk of ALS in Polish population, the results of meta-analysis suggest that the TT genotype can be a genetic risk factor for ALS in Caucasian population. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  9. Differential factors associated with challenge-proven food allergy phenotypes in a population cohort of infants: a latent class analysis.

    PubMed

    Peters, R L; Allen, K J; Dharmage, S C; Lodge, C J; Koplin, J J; Ponsonby, A-L; Wake, M; Lowe, A J; Tang, M L K; Matheson, M C; Gurrin, L C

    2015-05-01

    Food allergy, eczema and wheeze are early manifestations of allergic disease and commonly co-occur in infancy although their interrelationship is not well understood. Data from population studies are essential to determine whether there are differential drivers of multi-allergy phenotypes. We aimed to define phenotypes and risk factors of allergic disease using latent class analysis (LCA). The HealthNuts study is a prospective, population-based cohort of 5276 12-month-old infants in Melbourne, Australia. LCA was performed using the following baseline data collected at age 12 months: food sensitization (skin prick test ≥ 2 mm) and allergy (oral food challenge) to egg, peanut and sesame; early (< 4 months) and late-onset eczema; and wheeze in the first year of life. Risk factors were modelled using multinomial logistic regression. Five distinct phenotypes were identified: no allergic disease (70%), non-food-sensitized eczema (16%), single egg allergy (9%), multiple food allergies (predominantly peanut) (3%) and multiple food allergies (predominantly egg) (2%). Compared to the baseline group of no allergic disease, shared risk factors for all allergic phenotypes were parents born overseas (particularly Asia), delayed introduction of egg, male gender (except for single egg allergy) and family history of allergic disease, whilst exposure to pet dogs was protective for all phenotypes. Other factors including filaggrin mutations, vitamin D and the presence of older siblings differed by phenotype. Multiple outcomes in infancy can be used to determine five distinct allergy phenotypes at the population level, which have both shared and separate risk factors suggesting differential mechanisms of disease. © 2014 John Wiley & Sons Ltd.

  10. Mutational analysis in podocin-associated hereditary nephrotic syndrome in Polish patients: founder effect in the Kashubian population.

    PubMed

    Lipska, Beata S; Balasz-Chmielewska, Irena; Morzuch, Lucyna; Wasielewski, Kacper; Vetter, Dominika; Borzecka, Halina; Drozdz, Dorota; Firszt-Adamczyk, Agnieszka; Gacka, Ewa; Jarmolinski, Tomasz; Ksiazek, Joanna; Kuzma-Mroczkowska, Elzbieta; Litwin, Mieczyslaw; Medynska, Anna; Silska, Magdalena; Szczepanska, Maria; Tkaczyk, Marcin; Wasilewska, Anna; Schaefer, Franz; Zurowska, Aleksandra; Limon, Janusz

    2013-08-01

    Hereditary nephrotic syndrome is caused by mutations in a number of different genes, the most common being NPHS2. The aim of the study was to identify the spectrum of NPHS2 mutations in Polish patients with the disease. A total of 141 children with steroid-resistant nephrotic syndrome (SRNS) were enrolled in the study. Mutational analysis included the entire coding sequence and intron boundaries of the NPHS2 gene. Restriction fragment length polymorphism (RFLP) and TaqMan genotyping assay were applied to detect selected NPHS2 sequence variants in 575 population-matched controls. Twenty patients (14 %) had homozygous or compound heterozygous NPHS2 mutations, the most frequent being c.1032delT found in 11 children and p.R138Q found in four patients. Carriers of the c.1032delT allele were exclusively found in the Pomeranian (Kashubian) region, suggesting a founder effect origin. The 14 % NPHS2 gene mutation detection rate is similar to that observed in other populations. The heterogeneity of mutations detected in the studied group confirms the requirement of genetic testing the entire NPHS2 coding sequence in Polish patients, with the exception of Kashubs, who should be initially screened for the c.1032delT deletion.

  11. The -116C/G polymorphism in XBP1 gene is associated with psychiatric illness in Asian population: A meta-analysis.

    PubMed

    Cheng, Dan; Zhang, Kan; Zhen, Guohua; Xue, Zheng

    2014-12-01

    X-box binding protein 1 (XBP1) is a pivotal transcription factor and plays an important role in the pathogenesis of psychiatric illness. The association between XBP1-116C/G polymorphism and risk of psychiatric illness has been investigated in different populations. However, the results of these studies remain conflicting. Therefore, we performed a systematic meta-analysis to evaluate the association between XBP1-116C/G polymorphism and the overall psychiatric illness risk. Pubmed, Embase, and Chinese Biomedical Literature Database (CBM) were searched for case-control studies on the association between XBP1-116C/G polymorphism and psychiatric illness risk published up to July 31, 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to access the strength of this association. Fourteen case-control studies including 3,512 cases and 4,889 controls were included. Overall, no significant association was found between XBP1-116C/G polymorphism and the risk of psychiatric illness (C/G vs. C/C: OR = 1.04, 95%CI = 0.92-1.17, P = 0.54). However, there was a significant association between this polymorphism and the psychiatric illness in Asian population (C/G vs. C/C: OR = 1.27, 95%CI = 1.00-1.61, P = 0.05; G/G + C/G vs. C/C: OR = 1.32, 95%CI = 1.05-1.65, P = 0.02). Furthermore, we found a significant association between XBP1-116C/G polymorphism and the risk of bipolar disorder in Asian population (C/G vs. C/C: OR = 1.81, 95%CI = 1.15-2.86, P = 0.01). The XBP1-116C/G polymorphism is associated with an increased risk of bipolar disorder in Asian population. © 2014 Wiley Periodicals, Inc.

  12. Genotyping-by-Sequencing-Based Genetic Analysis of African Rice Cultivars and Association Mapping of Blast Resistance Genes Against Magnaporthe oryzae Populations in Africa.

    PubMed

    Mgonja, Emmanuel M; Park, Chan Ho; Kang, Houxiang; Balimponya, Elias G; Opiyo, Stephen; Bellizzi, Maria; Mutiga, Samuel K; Rotich, Felix; Ganeshan, Veena Devi; Mabagala, Robert; Sneller, Clay; Correll, Jim; Zhou, Bo; Talbot, Nicholas J; Mitchell, Thomas K; Wang, Guo-Liang

    2017-09-01

    Understanding the genetic diversity of rice germplasm is important for the sustainable use of genetic materials in rice breeding and production. Africa is rich in rice genetic resources that can be utilized to boost rice productivity on the continent. A major constraint to rice production in Africa is rice blast, caused by the hemibiotrophic fungal pathogen Magnaporthe oryzae. In this report, we present the results of a genotyping-by-sequencing (GBS)-based diversity analysis of 190 African rice cultivars and an association mapping of blast resistance (R) genes and quantitative trait loci (QTLs). The 190 African cultivars were clustered into three groups based on the 184K single nucleotide polymorphisms generated by GBS. We inoculated the rice cultivars with six African M. oryzae isolates. Association mapping identified 25 genomic regions associated with blast resistance (RABRs) in the rice genome. Moreover, PCR analysis indicated that RABR_23 is associated with the Pi-ta gene on chromosome 12. Our study demonstrates that the combination of GBS-based genetic diversity population analysis and association mapping is effective in identifying rice blast R genes/QTLs that contribute to resistance against African populations of M. oryzae. The identified markers linked to the RABRs and 14 highly resistant cultivars in this study will be useful for rice breeding in Africa.

  13. Association between Interleukin-6 Gene Polymorphisms and Rheumatoid Arthritis in Chinese Han Population: A Case-Control Study and A Meta-analysis

    PubMed Central

    Li, Feng; Xu, Jing; Zheng, Jiatian; Sokolove, Jeremy; Zhu, Kai; Zhang, Yuanchao; Sun, Hongsheng; Evangelou, Evangelos; Pan, Zhenglun

    2014-01-01

    The aim of this study was to investigate the possible association in the interleukin-6 (IL-6) gene with Rheumatoid arthritis (RA) in Chinese Han population from Shandong Province. Target regions of IL-6 gene were amplified by polymerase chain reaction (PCR) and genotyped. A logistic regression analysis was performed to detect potential associations in our case-control sample, the odd ratio(OR) and 95% confidence intervals(CIs) were calculated. Furthermore, we systematically tracked all the published studies in the field and performed a meta-analysis for the single nucleotide polymorphisms (SNPs) under study. 256 RA patients and 331 healthy controls were recruited into the case-control study. We found allele frequencies of rs1800795, rs1800797 and rs1474347 in RA patients differ from control subjects (P = 0.016, 0.024, 0.020, respectively). Significant difference was observed in haplotype frequencies of GCCGCT between RA patients and controls (P = 0.0001, OR = 4.066, 95%CI = 1.891 ~ 8.746), while GGCGCT frequencies was found lower in RA than controls (P = 0.006, OR = 0.669, 95%CI = 0.501 ~ 0.894). The results of the meta-analysis showed association polymorphism within the IL-6 promoter with RA. These findings suggest that rare IL-6 gene polymorphisms may associate with RA susceptibility in Han Chinese populations; however further studies are needed to assess the validity of the association of IL-6 with RA. PMID:25030201

  14. Meta-analysis added power to identify variants in FTO associated with type 2 diabetes and obesity in the Asian population.

    PubMed

    Liu, Yun; Liu, Zhe; Song, Yiqing; Zhou, Daizhan; Zhang, Di; Zhao, Teng; Chen, Zhuo; Yu, Lan; Yang, Yifeng; Feng, Guoyin; Li, Jun; Zhang, Jie; Liu, Simin; Zhang, Zuofeng; He, Lin; Xu, He

    2010-08-01

    Several common variants in the intron 1 of FTO (fat mass and associated obesity) gene have been reliably associated with BMI and obesity in European populations. We analyzed two variants (rs9939609 and rs8050136) in 4,189 Chinese Han individuals and conducted a meta-analysis of published studies in Asian population to investigate whether these variants are associated with type 2 diabetes (T2D) and obesity in Asian population. In this study, both the minor allele A of rs9939609 and the minor allele A of rs805136 were associated with increased risk of T2D, independent of measures of BMI; the odds ratios (ORs) per copy of the risk allele were 1.19 for rs9939609 (95% confidence interval (CI), 1.04-1.37; P = 0.01) and 1.22 for rs8050136 (95% CI, 1.07-1.40; P = 0.004) after adjusting for age, sex, and BMI. Our results also showed association with risk of obesity (rs9939609: OR = 1.39 (95% CI 1.04-1.85), P = 0.02; rs8050136: OR = 1.45 (95% CI 1.09-1.93), P = 0.01) but no association with overweight. These results were consistent with the pooled results from our meta-analysis study (for diabetes, rs8050136, P = 1.3 x 10(-3); rs9939609, P = 9.8 x 10(-4); for obesity, rs8050136, P = 2.2 x 10(-7); rs9939609, P = 9.0 x 10(-9)). Our findings indicate that the two variants (rs9939609 and rs8050136) in the FTO gene contribute to obesity and T2D in the Asian populations.

  15. Diversity of Pea-Associated F. proliferatum and F. verticillioides Populations Revealed by FUM1 Sequence Analysis and Fumonisin Biosynthesis

    PubMed Central

    Waśkiewicz, Agnieszka; Stępień, Łukasz; Wilman, Karolina; Kachlicki, Piotr

    2013-01-01

    Fusarium proliferatum and F. verticillioides are considered as minor pathogens of pea (Pisum sativum L.). Both species can survive in seed material without visible disease symptoms, but still contaminating it with fumonisins. Two populations of pea-derived F. proliferatum and F. verticillioides strains were subjected to FUM1 sequence divergence analysis, forming a distinct group when compared to the collection strains originating from different host species. Furthermore, the mycotoxigenic abilities of those strains were evaluated on the basis of in planta and in vitro fumonisin biosynthesis. No differences were observed in fumonisin B (FB) levels measured in pea seeds (maximum level reached 1.5 μg g−1); however, in rice cultures, the majority of F. proliferatum genotypes produced higher amounts of FB1–FB3 than F. verticillioides strains. PMID:23470545

  16. Genome-wide analysis of CNV (copy number variation) and their associations with narcolepsy in a Japanese population.

    PubMed

    Yamasaki, Maria; Miyagawa, Taku; Toyoda, Hiromi; Khor, Seik-Soon; Koike, Asako; Nitta, Aino; Akiyama, Kumi; Sasaki, Tsukasa; Honda, Yutaka; Honda, Makoto; Tokunaga, Katsushi

    2014-05-01

    In humans, narcolepsy with cataplexy (narcolepsy) is a sleep disorder that is characterized by sleepiness, cataplexy and rapid eye movement (REM) sleep abnormalities. Narcolepsy is caused by a reduction in the number of neurons that produce hypocretin (orexin) neuropeptide. Both genetic and environmental factors contribute to the development of narcolepsy.Rare and large copy number variations (CNVs) reportedly play a role in the etiology of a number of neuropsychiatric disorders. Narcolepsy is considered a neurological disorder; therefore, we sought to investigate any possible association between rare and large CNVs and human narcolepsy. We used DNA microarray data and a CNV detection software application, PennCNV-Affy, to detect CNVs in 426 Japanese narcoleptic patients and 562 healthy individuals. Overall, we found a significant enrichment of rare and large CNVs (frequency ≤1%, size ≥100 kb) in the patients (case-control ratio of CNV count=1.54, P=5.00 × 10(-4)). Next, we extended a region-based association analysis by including CNVs with its size ≥30 kb. Rare and large CNVs in PARK2 region showed a significant association with narcolepsy. Four patients were assessed to carry duplications of the gene region, whereas no controls carried the duplication, which was further confirmed by quantitative PCR assay. This duplication was also found in 2 essential hypersomnia (EHS) patients out of 171 patients. Furthermore, a pathway analysis revealed enrichments of gene disruptions by rare and large CNVs in immune response, acetyltransferase activity, cell cycle regulation and regulation of cell development. This study constitutes the first report on the risk association between multiple rare and large CNVs and the pathogenesis of narcolepsy. In the future, replication studies are needed to confirm the associations.

  17. The association analysis of RELN and GRM8 genes with autistic spectrum disorder in Chinese Han population.

    PubMed

    Li, Hui; Li, Yun; Shao, Jie; Li, Rong; Qin, Yufeng; Xie, Chunhong; Zhao, Zhengyan

    2008-03-05

    The region on chromosome 7q stands out as the region of suggestive linkage to aetiology of autism with the greatest concordance in many independent genome-wide scans. RELN and GRM8, the two genes selected in this study, are located within this region. The protein products of both genes are considered to play a pivotal role in the development of the central nervous system. In addition, biochemical and neuroanatomical data indicated that RELN and GRM8 genes are likely involved in the pathogenesis of autistic disorder. Therefore, both RELN and GRM8 genes are considered to be not only the positional but also the functional candidate genes to autism for association research. In this study, we genotyped 12 single nucleotide polymorphisms (SNPs) located within the RELN and GRM8 genes in 213 children with autistic spectrum disorder (ASD) and 160 controls. A significant genetic association between SNP2 (located in intron 59 of RELN) and ASD was observed, and the log-additive model was accepted as the best inheritance model fitting this data (OR: 0.72, 95% CI: 0.54-0.97, P = 0.03). Haplotype-specific association analysis revealed that the result was consistent with the individual SNP study; the combination of SNP1/SNP2/SNP3/SNP4 which are in strong linkage disequilibrium (LD) (D' > 0.75) showed significant association with ASD (P = 0.027). Neither the single SNP nor the haplotype analysis showed significant association between ASD and the markers of GRM8 gene. Hence, our study suggested the possible involvement of RELN gene in the susceptibility to ASD. Future replications are warranted before definitive conclusion can be drawn. (c) 2007 Wiley-Liss, Inc.

  18. Association of GSTT1 and GSTM1 polymorphisms with early pregnancy loss in an Indian population and a meta-analysis.

    PubMed

    Nair, Rohini R; Khanna, Anuradha; Singh, Kiran

    2013-04-01

    Glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase Mu 1 (GSTM1) enzymes of the glutathione detoxification pathway protect the embryo from oxidative stress. This study investigated GSTT1 and GSTM1 in relation to their role in conferring genetic susceptibility to pregnancy loss. In a case-control study, 174 early pregnancy loss (EPL) patients, of which 130 were recurrent pregnancy loss (RPL) patients, and 180 healthy controls were investigated. Null genotypes of GSTT1 and GSTM1 were identified in duplex PCR reaction systems. Age-adjusted odds ratios (aOR) were calculated by logistic regression analysis. A meta-analysis was also conducted. The GSTT1 null genotype was significantly associated with EPL (aOR 4.47, P=0.004) and RPL (aOR 4.39, P=0.006). No significant association of the GSTM1 null genotype was found with RPL. In a meta-analysis study, the presence of the GSTM1 null genotype was shown to be a risk for RPL. The GSTT1 null genotype was not found to be a risk factor for pregnancy loss in the pooled population but its association with RPL was found in the Indian population. This study suggests that women carriers of GSTT1 and GSTM1 null genotypes are more often at genetic risk of pregnancy loss. Glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase mu 1 (GSTM1), enzymes of detoxification pathway, protect the embryo from oxidative stress. In the present study we have investigated GSTT1 and GSTM1 in relation to their role in conferring genetic susceptibility for early pregnancy loss (EPL) and recurrent pregnancy loss (RPL). Meta-analysis on the polymorphisms was conducted to support our findings that the presence of mutant genotypes at this site increases the risk of pregnancy loss. The GSTT1 null genotype was significantly associated with both EPL and RPL. In the meta-analysis, the overall result showed that the association between GSTM1 null genotype and risk for RPL was statistically significant. On comparing the GSTT1

  19. Association analysis between 12 genetic variants of ten genes and personality traits in a young chinese Han population.

    PubMed

    Gong, Pingyuan; Zheng, Anyun; Zhang, Kejin; Lei, Xu; Li, Fengchao; Chen, Dongmei; Chi, Wanyu; Tong, Xueli; Zheng, Zijian; Gao, Xiaocai; Zhang, Fuchang

    2010-09-01

    Some genes involved in neurotransmission synthesis and transmission have been hypothesized to affect personality traits. To investigate the possible roles of these genes in personality traits of 16 Personality Factor Questionnaire, we performed a population-based study in a young Chinese Han cohort. In the study, we selected some functional variations in ten candidate genes (COMT, DBH, DRD(2), DRD(3), DAT, MAOA, GRM(1), GRIN2B, 5-TH(2A), and 5-TH(6)) encoding components in dopamine, glutamate, and 5-hydroxytryptamine pathways. The results showed the T102C in 5-TH(2A) was associated with X3 (emotional and quiet alertness) and B (reasoning) (F = 4.71 and 6.23; p = 0.009 and 0.002), Val158Met in COMT with E (dominance) (F = 7.01; p = 0.0009), while the variations in DBH, DRD(2), DRD(3), MAOA, GRM(1), GRIN2B, and 5-TH(6) were not associated with any of the personality traits. This finding suggests that T102C in 5-TH(2A) and Val158Met in COMT play roles in some human personality traits.

  20. Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

    PubMed Central

    Wen, Wanqing; Zheng, Wei; Okada, Yukinori; Takeuchi, Fumihiko; Tabara, Yasuharu; Hwang, Joo-Yeon; Dorajoo, Rajkumar; Li, Huaixing; Tsai, Fuu-Jen; Yang, Xiaobo; He, Jiang; Wu, Ying; He, Meian; Zhang, Yi; Liang, Jun; Guo, Xiuqing; Sheu, Wayne Huey-Herng; Delahanty, Ryan; Guo, Xingyi; Kubo, Michiaki; Yamamoto, Ken; Ohkubo, Takayoshi; Go, Min Jin; Liu, Jian Jun; Gan, Wei; Chen, Ching-Chu; Gao, Yong; Li, Shengxu; Lee, Nanette R.; Wu, Chen; Zhou, Xueya; Song, Huaidong; Yao, Jie; Lee, I-Te; Long, Jirong; Tsunoda, Tatsuhiko; Akiyama, Koichi; Takashima, Naoyuki; Cho, Yoon Shin; Ong, Rick TH; Lu, Ling; Chen, Chien-Hsiun; Tan, Aihua; Rice, Treva K; Adair, Linda S.; Gui, Lixuan; Allison, Matthew; Lee, Wen-Jane; Cai, Qiuyin; Isomura, Minoru; Umemura, Satoshi; Kim, Young Jin; Seielstad, Mark; Hixson, James; Xiang, Yong-Bing; Isono, Masato; Kim, Bong-Jo; Sim, Xueling; Lu, Wei; Nabika, Toru; Lee, Juyoung; Lim, Wei-Yen; Gao, Yu-Tang; Takayanagi, Ryoichi; Kang, Dae-Hee; Wong, Tien Yin; Hsiung, Chao Agnes; Wu, I-Chien; Juang, Jyh-Ming Jimmy; Shi, Jiajun; Choi, Bo Youl; Aung, Tin; Hu, Frank; Kim, Mi Kyung; Lim, Wei Yen; Wang, Tzung-Dao; Shin, Min-Ho; Lee, Jeannette; Ji, Bu-Tian; Lee, Young-Hoon; Young, Terri L.; Shin, Dong Hoon; Chun, Byung-Yeol; Cho, Myeong-Chan; Han, Bok-Ghee; Hwu, Chii-Min; Assimes, Themistocles L.; Absher, Devin; Yan, Xiaofei; Kim, Eric; Kuo, Jane Z.; Kwon, Soonil; Taylor, Kent D.; Chen, Yii-Der I.; Rotter, Jerome I.; Qi, Lu; Zhu, Dingliang; Wu, Tangchun; Mohlke, Karen L.; Gu, Dongfeng; Mo, Zengnan; Wu, Jer-Yuarn; Lin, Xu; Miki, Tetsuro; Tai, E. Shyong; Lee, Jong-Young; Kato, Norihiro; Shu, Xiao-Ou; Tanaka, Toshihiro

    2014-01-01

    Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488–47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10−13), ALDH2/MYL2 (rs671, P = 3.40 × 10−11; rs12229654, P = 4.56 × 10−9), ITIH4 (rs2535633, P = 1.77 × 10−10) and NT5C2 (rs11191580, P = 3.83 × 10−8) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10−8) and an additional 14 at P < 1.0 × 10−3 with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity. PMID:24861553

  1. Meta-analysis of Genome-wide Association Studies of Asthma In Ethnically Diverse North American Populations

    PubMed Central

    Torgerson, Dara G.; Ampleford, Elizabeth J.; Chiu, Grace Y.; Gauderman, W. James; Gignoux, Christopher R.; Graves, Penelope E.; Himes, Blanca E.; Levin, Albert M.; Mathias, Rasika A.; Hancock, Dana B.; Baurley, James W.; Eng, Celeste; Stern, Debra A.; Celedón, Juan C.; Rafaels, Nicholas; Capurso, Daniel; Conti, David V.; Roth, Lindsey A.; Soto-Quiros, Manuel; Togias, Alkis; Li, Xingnan; Myers, Rachel A.; Romieu, Isabelle; Van Den Berg, David J.; Hu, Donglei; Hansel, Nadia N.; Hernandez, Ryan D.; Israel, Elliott; Salam, Muhammad T.; Galanter, Joshua; Avila, Pedro C.; Avila, Lydiana; Rodriquez-Santana, Jose R.; Chapela, Rocio; Rodriguez-Cintron, William; Diette, Gregory B.; Adkinson, N. Franklin; Abel, Rebekah A.; Ross, Kevin D.; Shi, Min; Faruque, Mezbah U.; Dunston, Georgia M.; Watson, Harold R.; Mantese, Vito J.; Ezurum, Serpil C.; Liang, Liming; Ruczinski, Ingo; Ford, Jean G.; Huntsman, Scott; Chung, Kian Fan; Vora, Hita; Li, Xia; Calhoun, William J.; Castro, Mario; Sienra-Monge, Juan J.; del Rio-Navarro, Blanca; Deichmann, Klaus A.; Heinzmann, Andrea; Wenzel, Sally E.; Busse, William W.; Gern, James E.; Lemanske, Robert F.; Beaty, Terri H.; Bleecker, Eugene R.; Raby, Benjamin A.; Meyers, Deborah A.; London, Stephanie J.; Gilliland, Frank D.; Burchard, Esteban G.; Martinez, Fernando D.; Weiss, Scott T.; Williams, L. Keoki; Barnes, Kathleen C.; Ober, Carole; Nicolae, Dan L.

    2011-01-01

    Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies (GWAS) of asthma in 5,416 asthma cases representing European Americans, African Americans/African Caribbeans, and Latinos, and replicated five regions among the most significant signals in 12,649 individuals from the same ethnic groups. Four were at previously reported loci on 17q21, and near the IL1RL1, TSLP, and IL33, genes, but we report for the first time that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a novel association with asthma in the PYHIN1, gene that was specific to individuals of African descent (p=3.9×10−9). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma. PMID:21804549

  2. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

    PubMed

    Torgerson, Dara G; Ampleford, Elizabeth J; Chiu, Grace Y; Gauderman, W James; Gignoux, Christopher R; Graves, Penelope E; Himes, Blanca E; Levin, Albert M; Mathias, Rasika A; Hancock, Dana B; Baurley, James W; Eng, Celeste; Stern, Debra A; Celedón, Juan C; Rafaels, Nicholas; Capurso, Daniel; Conti, David V; Roth, Lindsey A; Soto-Quiros, Manuel; Togias, Alkis; Li, Xingnan; Myers, Rachel A; Romieu, Isabelle; Van Den Berg, David J; Hu, Donglei; Hansel, Nadia N; Hernandez, Ryan D; Israel, Elliott; Salam, Muhammad T; Galanter, Joshua; Avila, Pedro C; Avila, Lydiana; Rodriquez-Santana, Jose R; Chapela, Rocio; Rodriguez-Cintron, William; Diette, Gregory B; Adkinson, N Franklin; Abel, Rebekah A; Ross, Kevin D; Shi, Min; Faruque, Mezbah U; Dunston, Georgia M; Watson, Harold R; Mantese, Vito J; Ezurum, Serpil C; Liang, Liming; Ruczinski, Ingo; Ford, Jean G; Huntsman, Scott; Chung, Kian Fan; Vora, Hita; Li, Xia; Calhoun, William J; Castro, Mario; Sienra-Monge, Juan J; del Rio-Navarro, Blanca; Deichmann, Klaus A; Heinzmann, Andrea; Wenzel, Sally E; Busse, William W; Gern, James E; Lemanske, Robert F; Beaty, Terri H; Bleecker, Eugene R; Raby, Benjamin A; Meyers, Deborah A; London, Stephanie J; Gilliland, Frank D; Burchard, Esteban G; Martinez, Fernando D; Weiss, Scott T; Williams, L Keoki; Barnes, Kathleen C; Ober, Carole; Nicolae, Dan L

    2011-07-31

    Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.

  3. Association between HTR2A T102C polymorphism and major depressive disorder: a meta-analysis in the Chinese population.

    PubMed

    Lin, Chun-Xia; Hu, Zhe; Yan, Ze-Ming; Li, Wen; Chen, Yu-Sen; Zhao, Jiang-Hao; Zhang, Liang-Qing; Zhao, Bin; Zhong, Wang-Tao; Feng, Du

    2015-01-01

    Although a number of studies have been conducted on the association between HTR2A T102C polymorphism and major depressive disorder (MDD) in Chinese, this association remains elusive and controversial. To clarify the effects of HTR2A T102C polymorphism on the risk of MDD, a meta-analysis was performed in the Chinese population. Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) till 5 May 2015. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations. Statistical analyses were conducted with Version 10.0 STATA statistical software. A total of 12 case-control studies including 1444 MDD cases and 1445 controls were involved in this meta-analysis. Overall, no significant association with MDD risk was provided in the Chinese population (C vs. T: OR=0.97, 95% CI: 0.81-1.17, 95%; CC vs. TT: OR=0.95, 95% CI: 0.65-1.37; CC+TC vs. TT: OR=0.96, 95% CI: 0.75-1.12; CC vs. TT+TC: OR=0.94, 95% CI: 0.78-1.12). In subgroup analyses stratified by geographic area and source of controls, no significant association was found in any of the subgroups. In conclusion, this meta-analysis indicate that the HTR2A T102C polymorphism is not associated with susceptibility to MDD in Chinese population.

  4. Association between HTR2A T102C polymorphism and major depressive disorder: a meta-analysis in the Chinese population

    PubMed Central

    Lin, Chun-Xia; Hu, Zhe; Yan, Ze-Ming; Li, Wen; Chen, Yu-Sen; Zhao, Jiang-Hao; Zhang, Liang-Qing; Zhao, Bin; Zhong, Wang-Tao; Feng, Du

    2015-01-01

    Although a number of studies have been conducted on the association between HTR2A T102C polymorphism and major depressive disorder (MDD) in Chinese, this association remains elusive and controversial. To clarify the effects of HTR2A T102C polymorphism on the risk of MDD, a meta-analysis was performed in the Chinese population. Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) till 5 May 2015. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations. Statistical analyses were conducted with Version 10.0 STATA statistical software. A total of 12 case-control studies including 1444 MDD cases and 1445 controls were involved in this meta-analysis. Overall, no significant association with MDD risk was provided in the Chinese population (C vs. T: OR=0.97, 95% CI: 0.81-1.17, 95%; CC vs. TT: OR=0.95, 95% CI: 0.65-1.37; CC+TC vs. TT: OR=0.96, 95% CI: 0.75-1.12; CC vs. TT+TC: OR=0.94, 95% CI: 0.78-1.12). In subgroup analyses stratified by geographic area and source of controls, no significant association was found in any of the subgroups. In conclusion, this meta-analysis indicate that the HTR2A T102C polymorphism is not associated with susceptibility to MDD in Chinese population. PMID:26885016

  5. Allelic association and extended haplotype analysis of the spinal muscular atrophy (SMA) candidate region in the French Candadian population

    SciTech Connect

    Simard, L.R.; Prescott, G.; Rochette, C. |

    1994-09-01

    SMA is a common lower motor neuron disease characterized by progressive proximal limb and trunk muscle weakness. Despite the wide range in phenotypic severity, all three clinical types of childhood SMAs map to chromosome 5q11.2-5q13.3. The proximal (D5S557) flanking markers span about 1 Mb. We have previously demonstrated significant linkage disequilibrium between D5S125, D5S435, D5S351, JK53CA1/2 and SMA in the French Canadian population. We now present data for three new DNA markers mapping between D5S435 and D5S557 kindly provided to us by Drs. B. Wirth (A31), A. Burghes (Ag1) and A. MacKenzie (CATT-40G1). We identified 10 different A31 Alleles whose frequencies were similar for both normal and SMA chromosomes. Ag1 is a complex multi-allelic marker and specific primers amplified 1 (Class I), 2 or rarely 3 (Class II) alleles per chromosome. We observed significant association between Ag1 and SMA. For example, the 100 bp Ag1 fragment was typed on 20 of 73 SMA chromosomes and 0 of 74 normal chromosomes (p=<10{sup -4}). We also observed significant association between Ag1 Class genotypes and phenotypic severity. Class I chromosomes predominated in Type I SMA (p=.001) while Type II SMA individuals were generally heterozygous Class I/Class II (p=.001). Finally, we provide evidence for allelic association between Type I SMA and CATT-40G1, a tri-allelic sublocus of CATT-1. All of our Type I SMA chromosomes (n=20) carried a null allele compared to 40% of normal chromosomes (p=<10{sup -4}). Extended haplotype analyses indicated that > 19% of French Canadian SMA chromosomes appear to be ancestrally related to two unique haplotypes indicating their utility for linkage disequilibrium mapping.

  6. Iron deficiency is associated with increased levels of blood cadmium in the Korean general population: Analysis of 2008-2009 Korean National Health and Nutrition Examination Survey data

    SciTech Connect

    Lee, Byung-Kook; Kim, Yangho

    2012-01-15

    Introduction: We present data from the Korean National Health and Nutrition Examination Survey 2008-2009 on the distribution of blood cadmium levels and their association with iron deficiency in a representative sample of the adult Korean population. Methods: Serum ferritin was categorized into three levels: low (serum ferritin <15.0 {mu}g/L), low normal (15.0-30.0 {mu}g/L for women and 15.0-50.0 for men), and normal ({>=}30.0 {mu}g/L for women and {>=}50.0 for men), and its association with blood cadmium level was assessed after adjustment for various demographic and lifestyle factors. Results: Geometric means of blood cadmium in the low serum ferritin group in women, men, and all participants were significantly higher than in the normal group. Additionally, multiple regression analysis after adjusting for various covariates showed that blood cadmium was significantly higher in the low-ferritin group in women, men, and all participants compared with the normal group. We also found an association between serum ferritin and blood cadmium among never-smoking participants. Discussion: We found, similar to other recent population-based studies, an association between iron deficiency and increased blood cadmium in men and women, independent of smoking status. The results of the present study show that iron deficiency is associated with increased levels of blood cadmium in the general population.

  7. Association between monoamine oxidase B A644G polymorphism and Parkinson's disease risk: a meta-analysis in the Chinese population.

    PubMed

    Liu, J J; Wang, W; Meng, M; Liang, C S; Zhang, J W

    2016-07-14

    Although various individual studies have evaluated the correlation between monoamine oxidase B (MAOB), polymorphism, and Parkinson's disease (PD), the results remain inconclusive. Therefore, we performed a meta-analysis in the Chinese population to provide comprehensive data on the association between the MAOB polymorphism and PD. Eligible studies were identified via databases such as PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine, throughout November 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strengths of these associations. Eight studies documenting a total of 1385 cases of PD and 1426 controls were included in this meta-analysis. Overall, no significant association was found between the MAOB A644G polymorphism and PD risk in the Chinese population. However, in subgroup analyses, where results were stratified by geographical areas and source of controls, increased risk for PD in Northern China was observed (allele A vs G: OR = 1.33, 95%CI = 1.11-1.58; AA vs GG: OR = 1.46, 95%CI = 1.09-1.97; AA + AG vs GG: OR = 1.42, 95%CI = 1.06-1.90). Similarly, population-based studies also showed significant association between the MAOB A644G polymorphism and PD risk among different populations (allele A vs G: OR = 1.29, 95%CI = 1.11-1.51; AA vs GG: OR = 1.41, 95%CI = 1.09-1.82; AA + AG vs GG: OR = 1.34, 95%CI = 1.04- 1.71). In conclusion, this meta-analysis provided evidence that the MAOB A644G polymorphism may contribute to PD development in Northern China. Further studies conducted in other ethnic groups are required for definite conclusions.

  8. Association between the PADI4 -94G/A polymorphism and rheumatoid arthritis: a meta-analysis in the Chinese population.

    PubMed

    Chang, H X

    2016-03-31

    Although a number of studies have been conducted on the association between the peptidylarginine deiminase (PADI4) -94G/A polymorphism and rheumatoid arthritis (RA) in the Chinese population, the association remains elusive and controversial. To clarify the impact of the PADI4 -94G/A polymorphism on the risk of RA, a meta-analysis was performed in the Chinese population. Related studies were identified from databases such as, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) up to May 21, 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of associations. A total of 10 studies with 2783 RA cases and 2887 controls were included in this meta-analysis. Overall, a significantly elevated risk of RA was associated with all variants of PADI4 -94G/A (A vs G: OR = 1.24, 95%CI = 1.15-1.34; AA + GA vs GG: OR = 1.45, 95%CI = 1.29-1.62; AA vs GG: OR = 1.49, 95%CI = 1.28-1.73; AA vs GG + GA: OR = 1.19, 95%CI = 1.04-1.35). Subgroup analyses stratified by geographic areas and source of controls revealed significant results in the population-based studies in North and South China. In conclusion, this meta-analysis showed that the PADI4 -94G/A variants may influence RA risk in the Chinese population. However, further studies with gene-gene and gene-environment interactions are required for definite conclusions.

  9. Association of occupation with prevalent hypertension in an elderly East German population: an exploratory cross-sectional analysis.

    PubMed

    Schumann, Barbara; Seidler, Andreas; Kluttig, Alexander; Werdan, Karl; Haerting, Johannes; Greiser, Karin Halina

    2011-04-01

    Hypertension is one of the most relevant risk factors for cardiovascular disease; however, little is known about differences in hypertension by occupation. The aim of this study was to explore the association between occupational group and prevalent hypertension. Cross-sectional data of the CARLA study were used, a representative sample of an East German population aged 45-83. Job titles of the current or last held occupation of 967 men and 808 women were coded using the German classification of occupation. Hypertension was defined as blood pressure of ≥140 mmHg (systolic), ≥90 mmHg (diastolic) or use of antihypertensives. Sex-stratified, age-adjusted prevalence risk ratios (PR) with 95% confidence intervals (CI) were calculated for 31 occupational groups. Hypertension was prevalent in 79% of the population. In men, highest age-adjusted prevalence ratios were observed in metal-processing workers, carpenters/painters, and electricians with PRs of 1.31 (CI 1.04-1.65), 1.28 (CI 1.00-1.64), and 1.21 (0.95-1.53), respectively, compared to office clerks. In women, highest PRs were found in technicians/forewomen, scrutinisers/storekeepers, and food-processing occupations with PR 1.28 (1.09-1.49), 1.23 (0.99-1.51), and 1.22 (1.01-1.48), respectively. Adjustment for education, smoking, body mass index, and current work hours did not fully explain occupational differences. Excluding currently non-working subjects lead to decreased PRs in men and to increased PR in women. Differences in the prevalences of hypertension by occupational group were only partly explained by conventional risk factors and may require workplace interventions targeted at high-risk occupations. Longitudinal data with large cohorts and work-related exposure assessment are needed to confirm a temporal relationship between occupation and incident hypertension.

  10. Association analysis of endothelial nitric oxide synthase G894T gene polymorphism and erectile dysfunction complaints in a population-based survey.

    PubMed

    Andersen, Monica L; Guindalini, Camila; Santos-Silva, Rogerio; Bittencourt, Lia Rita A; Tufik, Sergio

    2010-03-01

    Erectile dysfunction (ED) is a common disorder leading to a serious, negative impact on the quality of the patient's life. The gene encoding endothelial nitric oxide synthase (eNOS) is an interesting candidate gene for understanding the physiopathology of ED, as it is involved in the catalytic production of nitric oxide (NO), the neurotransmitter that plays a critical role in penile tumescence and erection. To evaluate a potential association between the G894T polymorphism in the eNOS gene and ED complaints in a population-based sample in São Paulo, Brazil. The prevalence of ED complaints was estimated according to the answer to the question "How would you describe your ability to get and keep an erection that is adequate for satisfactory intercourse?" ED was considered to be present if the response was "sometimes" or "never." A total of 449 men were enrolled in the study and answered an eight-item questionnaire to ascertain sexual performance/ED and satisfaction. The eNOS G894T polymorphism was genotyped using a standard polymerase chain reaction method. Univariate analysis demonstrated that ED was associated with diabetes, hypertension, sleep apnea severity, increasing age and body mass index, as well as testosterone levels (P < 0.05). Forward multiple regression models indicated that age was the only independent factor associated with ED in this population (odds ratio = 1.09; 95% CI 1.06-1.11; P < 0.0001). Genotypic and allelic analyses provided no evidence for an association between this polymorphism and the risk for ED complaints in this sample. Population stratification did not affect the association test results. This is the first study to examine the effect of polymorphisms in the eNOS gene and the risk for ED utilizing a case-control approach in the Brazilian population. Our results do not support a major role for eNOS gene polymorphisms in ED in this population.

  11. Lack of association between the connexin 37 C1019T gene polymorphism and coronary artery disease in a Chinese population: Meta-analysis of 2,206 subjects.

    PubMed

    Li, Yan-Yan; Qian, Yun; Zhou, Chuan-Wei

    2013-05-01

    The connexin 37 (Cx37) C1019T gene polymorphism has been suggested to be correlated with increased coronary artery disease (CAD) risk, but research results remain inconsistent. To explore the relationship between the Cx37 C1019T gene polymorphism and CAD in a Chinese population, the current meta-analysis of 6 individual studies involving 1,244 CAD patients and 962 controls was conducted. The pooled odds ratios (ORs) as well as the corresponding 95% confidence intervals (CIs) were estimated using a random- or fixed-effect model. No significant association was found between Cx37 C1019T gene polymorphism and CAD in the Chinese population under the allelic (OR=0.96; 95% CI=0.59-1.56, P=0.87), recessive (OR=0.77, 95% CI=0.28-2.08, P=0.60), dominant (OR=0.990, 95% CI=0.773-1.266, P=0.934), additive (OR=1.000, 95% CI=0.736-1.359, P=1.000), homozygous (OR=1.062, 95% CI=0.598-1.887, P=0.836) or heterozygous (OR=1.017, 95% CI=0.802-1.291, P=0.888) genetic models. Cx37 C1019T gene polymorphism was not suggested to be associated with CAD susceptibility in the Chinese population. In conclusion, no association was found between Cx37 C1019T gene polymorphism and CAD in the Chinese population.

  12. Assessment of association between common variants at 17q12 and prostate cancer risk-evidence from Serbian population and meta--analysis.

    PubMed

    Nikolić, Zorana Z; Branković, Ana S; Savić-Pavićević, Dušanka L J; Preković, Stefan M; Vukotić, Vinka D; Cerović, Snežana J; Filipović, Nataša N; Tomović, Saša M; Romac, Stanka P; Brajušković, Goran N

    2014-08-01

    This study aimed to evaluate possible association between genotypes and alleles of two 17q12 polymorphisms (rs3760511 and rs7501939) and prostate cancer (PCa) risk and progression. Two hundred seventy-one patients with PCa, 261 patients with benign prostatic hyperplasia (BPH), and 171 controls were included in the study. Single nucleotide polymorphisms (SNPs) were genotyped by using PCR followed by restriction fragment length (PCR-RFLP) analysis. We conducted meta-analysis of published studies regarding association of these SNPs with PCa risk. Evidence of positive association between the AC genotype of the SNP rs3760511 and BPH risk for the best-fitting overdominant model of association (BPH vs. controls comparison, p = 0.026; odds ratio [OR] = 1.58; 95% confidence interval [95%CI] 1.05-2.36) were obtained. The association between T allele of rs7501939 and PCa risk was determined in PCa versus controls comparison (p = 0.0032; OR = 0.66, 95%CI 0.50-0.87) with the best-fitting model of inheritance being log-additive. This variant was also found to be associated with the risk of BPH (p = 0.0023; OR = 0.65, 95%CI 0.49-0.86). We found no association between parameters of PCa progression and the analyzed SNPs. Meta-analysis showed strong association between these variants and PCa risk. Our study shows association between SNPs at locus 17q12 and the risk of prostatic diseases in Serbian population. At the same time, results of meta-analysis suggest the association of these SNPs with PCa risk.

  13. Association of CYP1A1 MspI polymorphism with oral cancer risk in Asian populations: a meta-analysis.

    PubMed

    Xu, J L; Xia, R; Sun, L; Min, X; Sun, Z H; Liu, C; Zhang, H; Zhu, Y M

    2016-05-23

    Numerous studies regarding the association between the CYP1A1 MspI polymorphism and oral cancer risk in Asian populations have shown controversial results. To get a more precise estimation of this relationship, we conducted a comprehensive meta-analysis. PubMed, the Cochrane Library, Elsevier Science Direct, Web of Knowledge, the Chinese National Knowledge Infrastructure, VIP, and Wan Fang Med Online were searched. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated using fixed-effects or random-effects models. Heterogeneity among studies was assessed using the Cochran Q test and I(2) statistics. Twelve articles including 1925 oral cancer patients and 2335 controls were ultimately included in the meta-analysis. Overall, the meta-analysis showed that the CYP1A1 MspI polymorphism was associated with oral cancer risk in Asians (m1/m1 vs m2/m2: OR = 0.46, 95%CI = 0.30-070, POR = 0.000; m1/m1 vs m1/m2+m2/m2: OR = 0.70, 95%CI = 0.51-0.98, POR = 0.037; m1/m1+m1/m2 vs m2/m2: OR = 0.48, 95%CI = 0.35-0.65, POR = 0.000). Subgroup analyses showed that the control source (hospital-based or population-based), the genotyping method [polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism], the country in which the study was conducted, and Hardy-Weinberg equilibrium (Yes or No) were positively related to the association. Sensitivity analysis suggested that the overall results showed no significant change in three genetic models when any one study was removed, and publication bias was undetected by the Egger test. The CYP1A1 MspI polymorphism may be associated with oral cancer risk in Asian populations.

  14. Replication Study in a Japanese Population of Six Susceptibility Loci for Type 2 Diabetes Originally Identified by a Transethnic Meta-Analysis of Genome-Wide Association Studies

    PubMed Central

    Matsuba, Ren; Imamura, Minako; Tanaka, Yasushi; Iwata, Minoru; Hirose, Hiroshi; Kaku, Kohei; Maegawa, Hiroshi; Watada, Hirotaka; Tobe, Kazuyuki; Kashiwagi, Atsunori; Kawamori, Ryuzo; Maeda, Shiro

    2016-01-01

    Aim We performed a replication study in a Japanese population to evaluate the association between type 2 diabetes and six susceptibility loci (TMEM154, SSR1, FAF1, POU5F1, ARL15, and MPHOSPH9) originally identified by a transethnic meta-analysis of genome-wide association studies (GWAS) in 2014. Methods We genotyped 7,620 Japanese participants (5,817 type 2 diabetes patients and 1,803 controls) for each of the single nucleotide polymorphisms (SNPs) using a multiplex polymerase chain reaction invader assay. The association of each SNP locus with the disease was evaluated using logistic regression analysis. Results Of the six SNPs examined in this study, four (rs6813195 near TMEM154, rs17106184 in FAF1, rs3130501 in POU5F1 and rs4275659 near MPHOSPH9) had the same direction of effect as in the original reports, but two (rs9505118 in SSR1 and rs702634 in ARL15) had the opposite direction of effect. Among these loci, rs3130501 and rs4275659 were nominally associated with type 2 diabetes (rs3130501; p = 0.017, odds ratio [OR] = 1.113, 95% confidence interval [CI] 1.019–1.215, rs4275659; p = 0.012, OR = 1.127, 95% CI 1.026–1.238, adjusted for sex, age and body mass index), but we did not observe a significant association with type 2 diabetes for any of the six evaluated SNP loci in our Japanese population. Conclusions Our results indicate that effects of the six SNP loci identified in the transethnic GWAS meta-analysis are not major among the Japanese, although SNPs in POU5F1 and MPHOSPH9 loci may have some effect on susceptibility to type 2 diabetes in this population. PMID:27115357

  15. Genome-wide association mapping and pathway analysis of leukosis incidence in a US Holstein cattle population.

    PubMed

    Abdalla, E A; Peñagaricano, F; Byrem, T M; Weigel, K A; Rosa, G J M

    2016-08-01

    Bovine leukosis virus is an oncogenic virus that infects B cells, causing bovine leukosis disease. This disease is known to have a negative impact on dairy cattle production and, because no treatment or vaccine is available, finding a possible genetic solution is important. Our objective was to perform a comprehensive genetic analysis of leukosis incidence in dairy cattle. Data on leukosis occurrence, pedigree and molecular information were combined into multitrait GBLUP models with milk yield (MY) and somatic cell score (SCS) to estimate genetic parameters and to perform whole-genome scans and pathway analysis. Leukosis data were available for 11 554 Holsteins daughters of 3002 sires from 112 herds in 16 US states. Genotypes from a 60K SNP panel were available for 961 of those bulls as well as for 2039 additional bulls. Heritability for leukosis incidence was estimated at about 8%, and the genetic correlations of leukosis disease incidence with MY and SCS were moderate at 0.18 and 0.20 respectively. The genome-wide scan indicated that leukosis is a complex trait, possibly modulated by many genes. The gene set analysis identified many functional terms that showed significant enrichment of genes associated with leukosis. Many of these terms, such as G-Protein Coupled Receptor Signaling Pathway, Regulation of Nucleotide Metabolic Process and different calcium-related processes, are known to be related to retrovirus infection. Overall, our findings contribute to a better understanding of the genetic architecture of this complex disease. The functional categories associated with leukosis may be useful in future studies on fine mapping of genes and development of dairy cattle breeding strategies. © 2016 Stichting International Foundation for Animal Genetics.

  16. Association between fluid intake and kidney function, and survival outcomes analysis: a nationwide population-based study

    PubMed Central

    Wu, Li-Wei; Chen, Wei-Liang; Liaw, Fang-Yih; Sun, Yu-Shan; Yang, Hui-Fang; Wang, Chung-Ching; Lin, Chien-Ming; Tsao, Yu-Tzu

    2016-01-01

    Objectives Fluid intake, one of the most common daily activities, has not been well studied in chronic kidney disease (CKD) populations, and clinical outcomes are rarely addressed. The aim of this nationwide study is to explore the influence of daily fluid intake on cardiovascular and all-cause mortality and its association with renal function. Design Observational cohort study. Participants In all, 2182 participants aged more than 20 years participated in the Third National Health and Nutrition Examination Survey (1988–1994). Main outcome measures Survival outcomes in patients with or without CKD, using multiple variable adjusted Cox proportional hazard models. Results In a longitudinal survey with a median follow-up length of 15.4 years, 1080 participants died and 473 cardiovascular deaths were recorded. For all-cause mortality in the CKD group, individuals in the highest quartile of fluid intake (≧3.576 L/day) had better survival outcomes than those in the lowest quartile of fluid intake (≤2.147 L/day) (p=0.029) after adjustment of several pertinent variables. Conclusions Although the interpretation of this observational study was limited by the failure to identify the compositions of ingested fluids, adequate hydration may offer some advantages in patients with CKD. However, the underlying pathophysiological mechanisms of the responses of normal and injured kidneys to chronic changes in fluid consumption warrant further investigation. PMID:27173809

  17. A serotonin transporter gene (SLC6A4) polymorphism is associated with reduced risk of irritable bowel syndrome in American and Asian population: a meta-analysis.

    PubMed

    Areeshi, Mohammed Y; Haque, Shafiul; Panda, Aditya K; Mandal, Raju K

    2013-01-01

    Association studies of serotonin transporter gene SLC6A4 I/S polymorphism and irritable bowel syndrome (IBS) have shown inconsistent and contradictory results among different populations. In the present study, meta-analysis was performed to evaluate the association between SLC6A4 I/S polymorphism and IBS susceptibility. Systemic assessment was performed for the published studies based on the association of SLC6A4 I/S polymorphism and IBS risk from PubMed (Medline), EMBASE search. A meta-analysis was done to appraise the said association. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic model. A total of twelve studies comprising 2068 IBS cases and 2076 controls were included in this meta-analysis. Overall, no significant results were obtained for S allele carrier (S vs. I: p=0.488; OR=1.073, 95% CI=0.879 to 1.311) Co-dominant (SS vs. II; p=0.587; OR=1.112, 95% CI=0.758 to 1.631), (IS vs. II; p=0.361; OR=0.878, 95% CI=0.665 to 1.160). Similarly, dominant (SS+IS vs. II: p=0.853; OR=0.974, 95% CI=0.736 to 1.288) and recessive (SS vs. II+IS: p=0.267; OR=1.172, 95% CI=0.886 to 1.522) genetic models did not demonstrate risk. In the subgroup population based analysis, reduced risks were found in American (IS vs. II: p=0.009; OR=0.685, 95% CI=0.516 to 0.908) and Asian (SS+IS vs. II; p=0.001; OR=0.116, 95% CI=0.068 to 0.197) population. However, no risk was observed in European population. This investigation clearly demonstrates that SLC6A4 (Ins/Del) polymorphism is associated with reduced risk of IBS in American and Asian population. However, future well-designed studies with stratified case control and biological characterization will be needed to validate this finding.

  18. Association of ApoE gene with type 2 diabetic nephropathy in a Chinese population: a meta-analysis of case-control studies.

    PubMed

    Zhang, Cheng; Li, Shengbing; Zhang, Xianxiang; Liu, Hua; Luo, Yong

    2015-10-01

    Studies based on Chinese populations reported that inconsistent results were found on the association of ApoE gene polymorphisms with type 2 diabetic nephropathy (T2DN). Therefore, we performed this meta-analysis to provide a reliable evaluation of the associations between ApoE gene polymorphisms and T2DN. MEDLINE, EMBASE, Chinese Wanfang database and Chinese VIP database were searched for studies that reported the associations of ApoE gene polymorphisms with type 2 diabetic nephropathy in a Chinese population up to Dec 2013. A meta-analysis was performed to assess heterogeneity and combine results by using software RevMan 4.3.1. Sensitivity analysis and publication bias were conducted. Data from 16 published studies involving 4320 individuals were eligible for inclusion. After heterogeneity test in each analysis, corresponding effect models were applied to quantitatively syntheses data. The ApoE allele e2 and genotype e2/e3 occurred more frequently in T2DN than in T2DNN and NC group. Their ORs and 95%CIs in T2DN were 1.75 (1.27-2.42) and 1.68 (1.20-2.38) when compared with T2DNN, respectively (P<0.05); 2.59 (1.74-3.85) and 2.43 (1.61-3.65) when compared with NC, respectively (P<0.05). The publication bias diagnostics test and sensitivity analysis confirmed the reliability and stability of this meta-analysis. These findings support the significant association between ApoE gene polymorphisms and T2DN. It was revealed that allele e2 and genotype e2/e3 were risk factors for T2DN and allele e3 and genotype e3/e3 played a protective role in T2DN. Further studies will be needed to confirm the conclusion.

  19. The association and predictive value analysis of metabolic syndrome combined with resting heart rate on cardiovascular autonomic neuropathy in the general Chinese population

    PubMed Central

    2013-01-01

    Background The purpose of this study was to explore the extent of associations of cardiovascular autonomic neuropathy (CAN) with metabolic syndrome (MetS) and resting heart reate (HR), and to evaluate the predictive value of MetS combined with HR on CAN in a large sample derived from a Chinese population. Materials and methods We conducted a large-scale, population-based, cross-sectional study to explore the relationships of CAN with MetS and resting HR. This study included 2092 participants aged 30–80 years, and a total of 387 subjects were diagnosed with CAN in our dataset. The associations of CAN with MetS and resting HR were assessed by a multivariate logistic regression (MLR) analysis (using subjects without CAN as a reference group) after controlling for potential confounding factors. The predictive performance of resting HR and MetS was evaluated using the area under the receiver-operating characteristic curve (AUC). Results A tendency toward increased CAN prevalence with increasing resting HR was reported (p for trend < 0.001). MLR analysis showed that MetS and resting HR were very significantly and independently associated with CAN (β = 0.495 for MetS and β = 0.952 for HR, P < 0.001 for both). Resting HR alone and combined with MetS (MetS-HR) strongly predicted CAN (AUC = 0.719, P < 0.001 for resting HR and AUC = 0.735, P < 0.001 for MetS-HR). Conclusion Our findings signify that MetS and resting HR were very significantly and independently associated with CAN in the general Chinese population. Resting HR and MetS-HR both have a high value in predicting CAN in the general population. PMID:24238358

  20. The association and predictive value analysis of metabolic syndrome combined with resting heart rate on cardiovascular autonomic neuropathy in the general Chinese population.

    PubMed

    Lu, Yu; Tang, Zi-Hui; Zeng, Fangfang; Li, Yiming; Zhou, Linuo

    2013-11-17

    The purpose of this study was to explore the extent of associations of cardiovascular autonomic neuropathy (CAN) with metabolic syndrome (MetS) and resting heart reate (HR), and to evaluate the predictive value of MetS combined with HR on CAN in a large sample derived from a Chinese population. We conducted a large-scale, population-based, cross-sectional study to explore the relationships of CAN with MetS and resting HR. This study included 2092 participants aged 30-80 years, and a total of 387 subjects were diagnosed with CAN in our dataset. The associations of CAN with MetS and resting HR were assessed by a multivariate logistic regression (MLR) analysis (using subjects without CAN as a reference group) after controlling for potential confounding factors. The predictive performance of resting HR and MetS was evaluated using the area under the receiver-operating characteristic curve (AUC). A tendency toward increased CAN prevalence with increasing resting HR was reported (p for trend < 0.001). MLR analysis showed that MetS and resting HR were very significantly and independently associated with CAN (β = 0.495 for MetS and β = 0.952 for HR, P < 0.001 for both). Resting HR alone and combined with MetS (MetS-HR) strongly predicted CAN (AUC = 0.719, P < 0.001 for resting HR and AUC = 0.735, P < 0.001 for MetS-HR). Our findings signify that MetS and resting HR were very significantly and independently associated with CAN in the general Chinese population. Resting HR and MetS-HR both have a high value in predicting CAN in the general population.

  1. MTHFR gene A1298C polymorphisms are associated with breast cancer risk among Chinese population: evidence based on an updated cumulative meta-analysis.

    PubMed

    Wang, Yadong; Yang, Haiyan; Duan, Guangcai

    2015-01-01

    Published studies on the association between methylenetetrahydrofolate reductase (MTHFR) gene A1298C polymorphisms and breast cancer risk among Chinese population have yielded conflicting results. The purpose of this study was to clarify the association between MTHFR gene A1298C polymorphisms and breast cancer risk among Chinese population. Systematic searches were performed through the database of Medline/PubMed, Science Direct, Elsevier, CNKI and Wanfang Medical Online. Overall, a significantly increased risk of breast cancer was observed among the subjects carrying MTHFR gene A1298C AC+CC genotype (odds ratio [OR]=1.05 with 95% confidence interval [CI]: 1.01-1.10) as compared to those carrying AA genotype among total Chinese population. We did not observe any significant association between MTHFR gene A1298C polymorphisms and the risk of breast cancer under the additional genetic models of AC vs. AA, CC vs. AA and C-allele vs. A-allele (OR=1.00 with 95% CI: 0.97-1.02, OR=1.01 with 95% CI: 1.00-1.02 and OR=1.00 with 95% CI: 0.99-1.02, respectively). The cumulative meta-analysis showed similar results. In subgroup analysis, we observed subjects carrying AC+CC genotype had an increased breast cancer risk compared with those carrying AA genotype among the studies of sample size less than 1000. We did not observe any significant association between MTHFR gene A1298C polymorphisms and breast cancer risk in additional subgroup analyses. Our results suggest that MTHFR gene A1298C AC+CC genotype may be a risk factor for the development of breast cancer among Chinese population. Well-designed studies with a large sample size are needed to further confirm our findings.

  2. Association analysis of p16 (CDKN2A) and RB1 polymorphisms with susceptibility to cervical cancer in Indian population.

    PubMed

    Thakur, Nisha; Hussain, Showket; Nasare, Vilas; Das, Bhudev C; Basir, Seemi Farhat; Bharadwaj, Mausumi

    2012-01-01

    The potent tumor suppressors P16 and RB1 are the key regulators of cell cycle machinery in eukaryotes. Polymorphisms in these genes play an important role in the outcome of various diseases including cancer. In the present study, we evaluated the association of p16 and RB1 polymorphisms with cervical cancer susceptibility in Indian population. We screened 150 histologically confirmed cervical cancer cases along with equal number of healthy controls with normal cervical cytology. PCR-RFLP method was employed for genotyping of SNPs in p16 C540G (rs11515), C580T (rs3088440) in the 3'-UTR of exon 3 and RB1 A153104G (rs4151580) located in the intron 18 and confirmed by direct sequencing. Both patients and controls were screened for HPV infection. In this case-control study 84.67% (127/150) of cases were found to be positive for HPV DNA sequence. Women carrying p16 C540G carrier genotypes 540 (CG/GG) may have protective effect for the development of cervical cancer (P=0.0001, OR=0.31, 95% CI=0.17-0.56). And SNP at C580T of p16 gene was found to be negatively associated with the risk of cervical cancer (P=0.0004, OR=0.04, 95% CI=0.002-0.63). p16 (540C/580T) has emerged as a major risk haplotype (P=0.033, OR=1.47, 95% CI=1.05-2.07) whereas p16 (540G/580T) as a chief protective haplotype (P=0.014, OR=0.39, 95% CI=0.18-0.83) for the development of cervical cancer among Indian women. Contrary to this, SNP at A153104G of RB1 gene showed statistically significant association (P=0.035, OR=1.69, 95% CI=1.06-2.68) with increased susceptibility for the development of cervical cancer. Our results suggest that single nucleotide polymorphisms in p16, RB1 genes may affect the susceptibility to cervical cancer collectively.

  3. Volatility and Growth in Populations of Rural Associations

    ERIC Educational Resources Information Center

    Wollebaek, Dag

    2010-01-01

    This article uses unique community-level data aggregated from censuses of associations to analyze growth and volatility in rural populations of grassroots associations. A qualitative comparative analysis (QCA) shows that the two main paths to growth were (1) centralization in polycephalous (multicentered) municipalities and (2) population growth…

  4. Volatility and Growth in Populations of Rural Associations

    ERIC Educational Resources Information Center

    Wollebaek, Dag

    2010-01-01

    This article uses unique community-level data aggregated from censuses of associations to analyze growth and volatility in rural populations of grassroots associations. A qualitative comparative analysis (QCA) shows that the two main paths to growth were (1) centralization in polycephalous (multicentered) municipalities and (2) population growth…

  5. Joint-multiple family linkage analysis predicts within-family variation better than single-family analysis of the maize nested association mapping population

    USDA-ARS?s Scientific Manuscript database

    Quantitative trait loci (QTL) mapping has been used to dissect the genetic architecture of a trait and predict phenotypes for marker-assisted selection. Many QTL mapping studies in plants have been limited to one biparental family population. Joint analysis of multiple biparental families offers an ...

  6. Population Analysis: Communicating in Context

    NASA Technical Reports Server (NTRS)

    Rajulu, Sudhakar; Thaxton, Sherry

    2008-01-01

    Providing accommodation to a widely varying user population presents a challenge to engineers and designers. It is often even difficult to quantify who is accommodated and who is not accommodated by designs, especially for equipment with multiple critical anthropometric dimensions. An approach to communicating levels of accommodation referred to as population analysis applies existing human factors techniques in novel ways. This paper discusses the definition of population analysis as well as major applications and case studies. The major applications of population analysis consist of providing accommodation information for multivariate problems and enhancing the value of feedback from human-in-the-loop testing. The results of these analyses range from the provision of specific accommodation percentages of the user population to recommendations of design specifications based on quantitative data. Such feedback is invaluable to designers and results in the design of products that accommodate the intended user population.

  7. A general semi-parametric approach to the analysis of genetic association studies in population-based designs.

    PubMed

    Lutz, Sharon; Yip, Wai-Ki; Hokanson, John; Laird, Nan; Lange, Christoph

    2013-02-28

    For genetic association studies in designs of unrelated individuals, current statistical methodology typically models the phenotype of interest as a function of the genotype and assumes a known statistical model for the phenotype. In the analysis of complex phenotypes, especially in the presence of ascertainment conditions, the specification of such model assumptions is not straight-forward and is error-prone, potentially causing misleading results. In this paper, we propose an alternative approach that treats the genotype as the random variable and conditions upon the phenotype. Thereby, the validity of the approach does not depend on the correctness of assumptions about the phenotypic model. Misspecification of the phenotypic model may lead to reduced statistical power. Theoretical derivations and simulation studies demonstrate both the validity and the advantages of the approach over existing methodology. In the COPDGene study (a GWAS for Chronic Obstructive Pulmonary Disease (COPD)), we apply the approach to a secondary, quantitative phenotype, the Fagerstrom nicotine dependence score, that is correlated with COPD affection status. The software package that implements this method is available. The flexibility of this approach enables the straight-forward application to quantitative phenotypes and binary traits in ascertained and unascertained samples. In addition to its robustness features, our method provides the platform for the construction of complex statistical models for longitudinal data, multivariate data, multi-marker tests, rare-variant analysis, and others.

  8. Association between fluid intake and kidney function, and survival outcomes analysis: a nationwide population-based study.

    PubMed

    Wu, Li-Wei; Chen, Wei-Liang; Liaw, Fang-Yih; Sun, Yu-Shan; Yang, Hui-Fang; Wang, Chung-Ching; Lin, Chien-Ming; Tsao, Yu-Tzu

    2016-05-12

    Fluid intake, one of the most common daily activities, has not been well studied in chronic kidney disease (CKD) populations, and clinical outcomes are rarely addressed. The aim of this nationwide study is to explore the influence of daily fluid intake on cardiovascular and all-cause mortality and its association with renal function. Observational cohort study. In all, 2182 participants aged more than 20 years participated in the Third National Health and Nutrition Examination Survey (1988-1994). Survival outcomes in patients with or without CKD, using multiple variable adjusted Cox proportional hazard models. In a longitudinal survey with a median follow-up length of 15.4 years, 1080 participants died and 473 cardiovascular deaths were recorded. For all-cause mortality in the CKD group, individuals in the highest quartile of fluid intake (≧3.576 L/day) had better survival outcomes than those in the lowest quartile of fluid intake (≤2.147 L/day) (p=0.029) after adjustment of several pertinent variables. Although the interpretation of this observational study was limited by the failure to identify the compositions of ingested fluids, adequate hydration may offer some advantages in patients with CKD. However, the underlying pathophysiological mechanisms of the responses of normal and injured kidneys to chronic changes in fluid consumption warrant further investigation. 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/

  9. Postmastectomy Radiation Therapy Is Associated With Improved Survival in Node-Positive Male Breast Cancer: A Population Analysis.

    PubMed

    Abrams, Matthew J; Koffer, Paul P; Wazer, David E; Hepel, Jaroslaw T

    2017-06-01

    Because of its rarity, there are no randomized trials investigating postmastectomy radiation therapy (PMRT) in male breast cancer. This study retrospectively examines the impact of PMRT in male breast cancer patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. The SEER database 8.3.2 was queried for men ages 20+ with a diagnosis of localized or regional nonmetastatic invasive ductal/lobular carcinoma from 1998 to 2013. Included patients were treated by modified radical mastectomy (MRM), with or without adjuvant external beam radiation. Univariate and multivariate analyses evaluated predictors for PMRT use after MRM. Kaplan-Meier overall survival (OS) curves of the entire cohort and a case-matched cohort were calculated and compared by the log-rank test. Cox regression was used for multivariate survival analyses. A total of 1933 patients were included in the unmatched cohort. There was no difference in 5-year OS between those who received PMRT and those who did not (78% vs 77%, respectively, P=.371); however, in the case-matched analysis, PMRT was associated with improved OS at 5 years (83% vs 54%, P<.001). On subset analysis of the unmatched cohort, PMRT was associated with improved OS in men with 1 to 3 positive nodes (5-year OS 79% vs 72% P=.05) and those with 4+ positive nodes (5-year OS 73% vs 53% P<.001). On multivariate analysis of the unmatched cohort, independent predictors for improved OS were use of PMRT: HR=0.551 (0.412-0.737) and estrogen receptor-positive disease: HR=0.577 (0.339-0.983). Predictors for a survival detriment were higher grade 3/4: HR=1.825 (1.105-3.015), larger tumor T2: HR=1.783 (1.357-2.342), T3/T4: HR=2.683 (1.809-3.978), higher N-stage: N1 HR=1.574 (1.184-2.091), N2/N3: HR=2.328 (1.684-3.218), black race: HR=1.689 (1.222-2.336), and older age 81+: HR=4.164 (1.497-11.582). There may be a survival benefit with the addition of PMRT for male breast cancer with node-positive disease

  10. GIS Early-Warning System for Vectors of Rift Valley Fever: Anomaly Analysis of Climate-Population Associations

    USDA-ARS?s Scientific Manuscript database

    A critical component of predicting the risk of transmission of mosquito-borne viruses is knowing the status of vector populations. Mosquito control agencies have good systems for measuring mosquito populations at county or district levels, but these data are not synthesized to regional or national ...

  11. [Meta-analysis of the association of Pro12Ala polymorphism of peroxisome proliferator activated receptor gamma gene with type 2 diabetes in Chinese Han population].

    PubMed

    Guo, Wu-Lan; Tang, Yong; Han, Xue-Yao; Ji, Li-Nong

    2011-12-01

    To evaluate the association of Pro12Ala polymorphism of peroxisome proliferator activated receptor gamma (PPARgamma) gene with type 2 diabetes (T2DM) in Chinese Han population. The present investigation was carried out using the keywords "PPARgamma", "pparg", "Pro12Ala", "type 2 diabetes", and "Chinese. The odds ratios (OR) for Ala12 used as the metric of choice were calculated in the dominant and additive model separately. The Meta-analysis was conducted by software STATA 11.0. (1) We identified 22 studies, of which 17 studies involving 3927 type 2 diabetes cases and 3364 controls fell into the inclusion criteria. The analysis indicated no significant inter-study heterogeneity and publication bias. (2) The frequencies of the minor allele Ala12 in type 2 diabetes and control groups were 4.8% and 4.6% respectively. (3) The combined overall OR of dominant and additive model calculated by fix-effects meta-analysis for type 2 diabetes and the Pro12Ala polymorphism, were 0.95 (95% CI: 0.80, 1.12) and 0.93 (95% CI: 0.79, 1.09) respectively. In this meta-analysis, the Pro12Ala gene variant (rs1801282) is not found to be associated with the susceptibility for type 2 diabetes in Chinese Han population.

  12. Associations of All-Cause Mortality with Census-Based Neighbourhood Deprivation and Population Density in Japan: A Multilevel Survival Analysis

    PubMed Central

    Nakaya, Tomoki; Honjo, Kaori; Hanibuchi, Tomoya; Ikeda, Ai; Iso, Hiroyasu; Inoue, Manami; Sawada, Norie; Tsugane, Shoichiro

    2014-01-01

    Background Despite evidence that neighbourhood conditions affect residents' health, no prospective studies of the association between neighbourhood socio-demographic factors and all-cause mortality have been conducted in non-Western societies. Thus, we examined the effects of areal deprivation and population density on all-cause mortality in Japan. Methods We employed census and survival data from the Japan Public Health Center-based Prospective Study, Cohort I (n = 37,455), consisting of middle-aged residents (40 to 59 years at the baseline in 1990) living in four public health centre districts. Data spanned between 1990 and 2010. A multilevel parametric proportional-hazard regression model was applied to estimate the hazard ratios (HRs) of all-cause mortality by two census-based areal variables —areal deprivation index and population density—as well as individualistic variables such as socioeconomic status and various risk factors. Results We found that areal deprivation and population density had moderate associations with all-cause mortality at the neighbourhood level based on the survival data with 21 years of follow-ups. Even when controlling for individualistic socio-economic status and behavioural factors, the HRs of the two areal factors (using quartile categorical variables) significantly predicted mortality. Further, this analysis indicated an interaction effect of the two factors: areal deprivation prominently affects the health of residents in neighbourhoods with high population density. Conclusions We confirmed that neighbourhood socio-demographic factors are significant predictors of all-cause death in Japanese non-metropolitan settings. Although further study is needed to clarify the cause-effect relationship of this association, the present findings suggest that health promotion policies should consider health disparities between neighbourhoods and possibly direct interventions towards reducing mortality in densely populated and highly

  13. Associations of all-cause mortality with census-based neighbourhood deprivation and population density in Japan: a multilevel survival analysis.

    PubMed

    Nakaya, Tomoki; Honjo, Kaori; Hanibuchi, Tomoya; Ikeda, Ai; Iso, Hiroyasu; Inoue, Manami; Sawada, Norie; Tsugane, Shoichiro

    2014-01-01

    Despite evidence that neighbourhood conditions affect residents' health, no prospective studies of the association between neighbourhood socio-demographic factors and all-cause mortality have been conducted in non-Western societies. Thus, we examined the effects of areal deprivation and population density on all-cause mortality in Japan. We employed census and survival data from the Japan Public Health Center-based Prospective Study, Cohort I (n = 37,455), consisting of middle-aged residents (40 to 59 years at the baseline in 1990) living in four public health centre districts. Data spanned between 1990 and 2010. A multilevel parametric proportional-hazard regression model was applied to estimate the hazard ratios (HRs) of all-cause mortality by two census-based areal variables--areal deprivation index and population density--as well as individualistic variables such as socioeconomic status and various risk factors. We found that areal deprivation and population density had moderate associations with all-cause mortality at the neighbourhood level based on the survival data with 21 years of follow-ups. Even when controlling for individualistic socio-economic status and behavioural factors, the HRs of the two areal factors (using quartile categorical variables) significantly predicted mortality. Further, this analysis indicated an interaction effect of the two factors: areal deprivation prominently affects the health of residents in neighbourhoods with high population density. We confirmed that neighbourhood socio-demographic factors are significant predictors of all-cause death in Japanese non-metropolitan settings. Although further study is needed to clarify the cause-effect relationship of this association, the present findings suggest that health promotion policies should consider health disparities between neighbourhoods and possibly direct interventions towards reducing mortality in densely populated and highly deprived neighbourhoods.

  14. A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Paediatric Cohorts

    PubMed Central

    Groen-Blokhuis, Maria M.; Pourcain, Beate St.; Greven, Corina U.; Pappa, Irene; Tiesler, Carla M.T.; Ang, Wei; Nolte, Ilja M.; Vilor-Tejedor, Natalia; Bacelis, Jonas; Ebejer, Jane L.; Zhao, Huiying; Davies, Gareth E.; Ehli, Erik A.; Evans, David M.; Fedko, Iryna O.; Guxens, Mònica; Hottenga, Jouke-Jan; Hudziak, James J.; Jugessur, Astanand; Kemp, John P.; Krapohl, Eva; Martin, Nicholas G.; Murcia, Mario; Myhre, Ronny; Ormel, Johan; Ring, Susan M.; Standl, Marie; Stergiakouli, Evie; Stoltenberg, Camilla; Thiering, Elisabeth; Timpson, Nicholas J.; Trzaskowski, Maciej; van der Most, Peter J.; Wang, Carol; Nyholt, Dale R.; Medland, Sarah E.; Neale, Benjamin; Jacobsson, Bo; Sunyer, Jordi; Hartman, Catharina A.; Whitehouse, Andrew J.O.; Pennell, Craig E.; Heinrich, Joachim; Plomin, Robert; Smith, George Davey; Tiemeier, Henning; Posthuma, Danielle; Boomsma, Dorret I.

    2016-01-01

    Objective To elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. Method Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (< 13 years) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. Results SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46×10-6 and 2.66×10-6). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. Conclusion The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and improve statistical power for identifying genetic variants. PMID:27663945

  15. A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts.

    PubMed

    Middeldorp, Christel M; Hammerschlag, Anke R; Ouwens, Klaasjan G; Groen-Blokhuis, Maria M; Pourcain, Beate St; Greven, Corina U; Pappa, Irene; Tiesler, Carla M T; Ang, Wei; Nolte, Ilja M; Vilor-Tejedor, Natalia; Bacelis, Jonas; Ebejer, Jane L; Zhao, Huiying; Davies, Gareth E; Ehli, Erik A; Evans, David M; Fedko, Iryna O; Guxens, Mònica; Hottenga, Jouke-Jan; Hudziak, James J; Jugessur, Astanand; Kemp, John P; Krapohl, Eva; Martin, Nicholas G; Murcia, Mario; Myhre, Ronny; Ormel, Johan; Ring, Susan M; Standl, Marie; Stergiakouli, Evie; Stoltenberg, Camilla; Thiering, Elisabeth; Timpson, Nicholas J; Trzaskowski, Maciej; van der Most, Peter J; Wang, Carol; Nyholt, Dale R; Medland, Sarah E; Neale, Benjamin; Jacobsson, Bo; Sunyer, Jordi; Hartman, Catharina A; Whitehouse, Andrew J O; Pennell, Craig E; Heinrich, Joachim; Plomin, Robert; Smith, George Davey; Tiemeier, Henning; Posthuma, Danielle; Boomsma, Dorret I

    2016-10-01

    The aims of this study were to elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (<13 years of age) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46 × 10(-6) and 2.66 × 10(-6)). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture, and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and to improve statistical power for identifying genetic variants. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights

  16. SNP discovery in common bean by restriction-associated DNA (RAD) sequencing for genetic diversity and population structure analysis.

    PubMed

    Valdisser, Paula Arielle M R; Pappas, Georgios J; de Menezes, Ivandilson P P; Müller, Bárbara S F; Pereira, Wendell J; Narciso, Marcelo G; Brondani, Claudio; Souza, Thiago L P O; Borba, Tereza C O; Vianello, Rosana P

    2016-06-01

    Researchers have made great advances into the development and application of genomic approaches for common beans, creating opportunities to driving more real and applicable strategies for sustainable management of the genetic resource towards plant breeding. This work provides useful polymorphic single-nucleotide polymorphisms (SNPs) for high-throughput common bean genotyping developed by RAD (restriction site-associated DNA) sequencing. The RAD tags were generated from DNA pooled from 12 common bean genotypes, including breeding lines of different gene pools and market classes. The aligned sequences identified 23,748 putative RAD-SNPs, of which 3357 were adequate for genotyping; 1032 RAD-SNPs with the highest ADT (assay design tool) score are presented in this article. The RAD-SNPs were structurally annotated in different coding (47.00 %) and non-coding (53.00 %) sequence components of genes. A subset of 384 RAD-SNPs with broad genome distribution was used to genotype a diverse panel of 95 common bean germplasms and revealed a successful amplification rate of 96.6 %, showing 73 % of polymorphic SNPs within the Andean group and 83 % in the Mesoamerican group. A slightly increased He (0.161, n = 21) value was estimated for the Andean gene pool, compared to the Mesoamerican group (0.156, n = 74). For the linkage disequilibrium (LD) analysis, from a group of 580 SNPs (289 RAD-SNPs and 291 BARC-SNPs) genotyped for the same set of genotypes, 70.2 % were in LD, decreasing to 0.10 %in the Andean group and 0.77 % in the Mesoamerican group. Haplotype patterns spanning 310 Mb of the genome (60 %) were characterized in samples from different origins. However, the haplotype frameworks were under-represented for the Andean (7.85 %) and Mesoamerican (5.55 %) gene pools separately. In conclusion, RAD sequencing allowed the discovery of hundreds of useful SNPs for broad genetic analysis of common bean germplasm. From now, this approach provides an excellent panel

  17. Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.

    PubMed

    Wen, Wanqing; Zheng, Wei; Okada, Yukinori; Takeuchi, Fumihiko; Tabara, Yasuharu; Hwang, Joo-Yeon; Dorajoo, Rajkumar; Li, Huaixing; Tsai, Fuu-Jen; Yang, Xiaobo; He, Jiang; Wu, Ying; He, Meian; Zhang, Yi; Liang, Jun; Guo, Xiuqing; Sheu, Wayne Huey-Herng; Delahanty, Ryan; Guo, Xingyi; Kubo, Michiaki; Yamamoto, Ken; Ohkubo, Takayoshi; Go, Min Jin; Liu, Jian Jun; Gan, Wei; Chen, Ching-Chu; Gao, Yong; Li, Shengxu; Lee, Nanette R; Wu, Chen; Zhou, Xueya; Song, Huaidong; Yao, Jie; Lee, I-Te; Long, Jirong; Tsunoda, Tatsuhiko; Akiyama, Koichi; Takashima, Naoyuki; Cho, Yoon Shin; Ong, Rick Th; Lu, Ling; Chen, Chien-Hsiun; Tan, Aihua; Rice, Treva K; Adair, Linda S; Gui, Lixuan; Allison, Matthew; Lee, Wen-Jane; Cai, Qiuyin; Isomura, Minoru; Umemura, Satoshi; Kim, Young Jin; Seielstad, Mark; Hixson, James; Xiang, Yong-Bing; Isono, Masato; Kim, Bong-Jo; Sim, Xueling; Lu, Wei; Nabika, Toru; Lee, Juyoung; Lim, Wei-Yen; Gao, Yu-Tang; Takayanagi, Ryoichi; Kang, Dae-Hee; Wong, Tien Yin; Hsiung, Chao Agnes; Wu, I-Chien; Juang, Jyh-Ming Jimmy; Shi, Jiajun; Choi, Bo Youl; Aung, Tin; Hu, Frank; Kim, Mi Kyung; Lim, Wei Yen; Wang, Tzung-Dao; Shin, Min-Ho; Lee, Jeannette; Ji, Bu-Tian; Lee, Young-Hoon; Young, Terri L; Shin, Dong Hoon; Chun, Byung-Yeol; Cho, Myeong-Chan; Han, Bok-Ghee; Hwu, Chii-Min; Assimes, Themistocles L; Absher, Devin; Yan, Xiaofei; Kim, Eric; Kuo, Jane Z; Kwon, Soonil; Taylor, Kent D; Chen, Yii-Der I; Rotter, Jerome I; Qi, Lu; Zhu, Dingliang; Wu, Tangchun; Mohlke, Karen L; Gu, Dongfeng; Mo, Zengnan; Wu, Jer-Yuarn; Lin, Xu; Miki, Tetsuro; Tai, E Shyong; Lee, Jong-Young; Kato, Norihiro; Shu, Xiao-Ou; Tanaka, Toshihiro

    2014-10-15

    Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Association between killer cell immunoglobulin-like receptor (KIR) polymorphisms and systemic lupus erythematosus (SLE) in populations: A PRISMA-compliant meta-analysis.

    PubMed

    Liang, Hui-Ling; Ma, Shu-Juan; Tan, Hong-Zhuan

    2017-03-01

    Recently, a growing number of studies show that the killer cell immunoglobulin-like receptor (KIR) gene polymorphisms may play a role in the systemic lupus erythematosus (SLE) susceptibility. Nonetheless, the results were inconsistent. Thus, a meta-analysis was carried out by integrating multiple research to clarify the association between KIR polymorphisms and SLE susceptibility. The Web of Science, Embase (Ovid), PubMed, Elsevier Science Direct, the Chinese Biomedical Database and CNKI, Wanfang databases (last search was updated on May 15, 2016) were systematically searched to select studies on addressing the association between the KIR polymorphisms and susceptibility to SLE in populations. The odds ratio (OR) with 95% confidence interval (95% CI) was calculated. A total of 10 published case-control studies involving 1450 SLE patients and 1758 controls were available for this meta-analysis. Results suggested that KIR2DL1 might be a risk factor for SLE (OR 2DL1 =1.047, 95% CI=1.011-1.083) in all subjects. The KIR2DL3, KIR2DL5 were identified as protective factors for SLE in Asian populations (OR2DL3= 0.215, 95% CI = 0.077-0.598; OR2DL5 = 0.588, 95% CI = 0.393-0.881), but not in Caucasians. The meta-analysis results suggested that 2DL1 might be a potential risk factor and 2DL3, 2DL5 might be protective factors for SLE in Asians but not in Caucasians.

  19. Association of interleukin 1 receptor antagonist (IL1RN) gene polymorphism with recurrent pregnancy loss risk in the North Indian Population and a meta-analysis.

    PubMed

    Nair, Rohini Ravindran; Khanna, Anuradha; Singh, Kiran

    2014-09-01

    An appropriate ratio of interleukin 1 beta to interleukin 1 receptor antagonist (IL1Ra) is required for successful pregnancy. Our objective was to study the genetic association between IL1RN variable numbers of tandem repeat (VNTR) polymorphism and recurrent pregnancy loss (RPL). To analyze the association between IL1RN VNTR allele and RPL, we investigated the IL1RN VNTR polymorphism in 136 RPL patients and in 200 healthy control women. Meta-analysis on this polymorphism was conducted to support our findings. PCR based approach was used to analyze IL1RN VNTR polymorphism and it was further confirmed by sequencing. Systematic review and meta-analysis was done using electronic database (Pub-Med, Google Scholar and Ovid) up to February 27, 2013. This meta-analysis was assessed by comprehensive meta-analysis software version 2. For meta-analysis 549 cases and 1,450 controls were included. The frequency of IL1RN genotype 2/2 was significantly higher in RPL compared to control group (AORs 3.10, 95 % CI 1.58-6.11, p = 0.001). The presence of rare allele also increased the risk of RPL significantly (ORs 1.63, 95 % CI 1.16-2.29, p = 0.004). The meta-analysis stratified by ethnicity showed that individuals with allele 2 had increased risk of RPL (OR 1.29, 95 % CI 1.04-1.61, p = 0.01), in Asians population by using fixed model. However the data of the present study clearly suggests that IL1RN VNTR polymorphism is a genetic risk factor for pregnancy loss in the study population.

  20. Random amplified polymorphic DNA analysis of kinship within host-associated populations of the symbiotic water mite Unionicola foili (Acari: Unionicolidae).

    PubMed

    Edwards, Dale D; Deatherage, Daniel E; Ernsting, Brian R

    2004-01-01

    Kinship relations within populations of unionicolid water mites are not well known, owing to their complex life cycles and the fact that interactions between active and resting stages for some species are transitory. A number of species of unionicolid water mites are, however, obligate symbionts of freshwater mussels and spend most of their life cycle in association with these hosts. Among these species of mites, parents and offspring are more likely to co-occur and thus provide opportunities to address questions related to the structure of the mating system. The present study employs random amplified polymorphic DNA (RAPD) analysis to address kinship within populations of Unionicola foili living in symbiotic association with the host mussel Utterbackia imbecillis. DNA was amplified from adult mites and a representative number of eggs or larvae (n = 20-30) that were removed from mussels collected on three separate occasions (July, November, and March) over a 12-month period. Parsimony analyses of the molecular data for adults and progeny collected from mussels during July, November, and March revealed distinct groupings, that for the most part, corresponded to mites collected from each of the sampling periods. Many of the genetic markers obtained for male and female U. foili were not evident among the larvae or eggs, suggesting that adults obtained from a host mussel at the time of collection were not the parents of a majority of the progeny. However, female mites and eggs collected from mussels during March and November shared more markers than did females and progeny examined during July. Furthermore, many offspring in the July sampling period were found to have one or more parents absent from the sampled population. Overall, RAPD profiling appears to have limited usage in determining kinship within populations of U. foili, due to its recruitment patterns, and the relatively large number of adults and progeny per mussel. It may, however, prove to be a useful

  1. ADH1B Arg47His polymorphism is associated with esophageal cancer risk in high-incidence Asian population: evidence from a meta-analysis.

    PubMed

    Zhang, Guohong; Mai, Ruiqin; Huang, Bo

    2010-10-27

    Incidence of Esophageal squamous cell carcinoma (ESCC) is prevalent in Asian populations, especially in the ones from the "Asian esophageal cancer belt" along the Silk Road and the ones from East Asia (including Japan). Silk Road and Eastern Asia population genetics are relevant to the ancient population migration from central China. The Arg47His (rs1229984) polymorphism of ADH1B is the highest in East Asians, and ancient migrations along the Silk Road were thought to be contributive to a frequent ADH1B*47His allele in Central Asians. This polymorphism was identified as responsible for susceptibility in the first large-scale genome-wide association study of ESCC and that's explained by its modulation of alcohol oxidization capability. To investigate the association of ADH1B Arg47His with ESCC in Asian populations under a common ancestry scenario of the susceptibility loci, we combined all available studies into a meta-analysis. A dataset composed of 4,220 cases and 8,946 controls from twelve studies of Asian populations was analyzed for ADH1B Arg47His association with ESCC and its interactions with alcohol drinking and ALDH2 Glu504Lys. Heterogeneity among studies and their publication bias were also tested. The ADH1B*47Arg allele was found to be associated to increased risk of ESCC, with the odds ratios (OR) being 1.62 (95% CI: 1.49-1.76) and 3.86 (2.96-5.03) for the His/Arg and the Arg/Arg genotypes, respectively. When compared with the His/His genotype of non-drinkers, the Arg/Arg genotype can interact with alcohol drinking and greatly increase the risk of ESCC (OR = 20.69, 95%CI: 5.09-84.13). Statistical tests also showed gene-gene interaction of ADH1B Arg+ with ALDH2 Lys+ can bring more risk to ESCC (OR  = 13.46, 95% CI: 2.32-78.07). Revealed by this meta-analysis, ADH1B*47Arg as a common ancestral allele can significantly increase the risk of ESCC in Asians, especially when coupled with alcohol drinking or the ALDH2*504Lys allele.

  2. Analysis of Mechanisms Associated with Loss of Infectivity of Clonal Populations of Borrelia burgdorferi B31MI

    PubMed Central

    McDowell, John V.; Sung, Shian Ying; Labandeira-Rey, Maria; Skare, Jon T.; Marconi, Richard T.

    2001-01-01

    Numerous studies have provided suggestive evidence that the loss of plasmids correlates with the loss of infectivity of the Lyme disease spirochetes. In this study we have further investigated this correlation. Clonal populations were obtained from the skin of a mouse infected for 3 months with a clonal population of Borrelia burgdorferi B31MI. The complete plasmid compositions of these populations were determined using a combination of PCR and Southern hybridization. The infectivities of clones differing in plasmid composition were tested using the C3H-HeJ murine model for Lyme disease. While several clones were found to be noninfectious, a correlation between the loss of a specific plasmid and loss of infectivity in the clones analyzed in this report was not observed. While it is clear from recent studies that the loss of some specific plasmids results in attenuated virulence, this study demonstrates that additional mechanisms also contribute to the loss of infectivity. PMID:11349029

  3. Examining the work–crime association in emerging adulthood: A longitudinal analysis based on a Dutch population sample

    PubMed Central

    Wensveen, Maaike; Palmen, Hanneke; Blokland, Arjan; Meeus, Wim

    2016-01-01

    Social control theory links being employed with reduced criminal behaviour. In particular, the indirect social control generated by the perceived benefits of the current job are expected to underlie the work–crime association. Features specific to the emerging adult period, however, call into question the strength of the work–crime association during this new life stage. This study uses data from the Utrecht Study of Adolescent Development (USAD), a longitudinal self-report study among 669 men and women aged 18 to 24 at the start of the study to examine the extent to which working a paid job is associated with reduced levels of delinquency and crime, and the extent to which this association is conditional on individual job perceptions. We also test for gender differences in these associations. Results indicate that for men – but not for women – paid work is associated with lower levels of delinquency and crime, but only from age 24 onwards. PMID:28781582

  4. Analysis of Factors Associated With Sagittal Balance in Normal Asymptomatic Individuals: A Retrospective Study in a Population of East China.

    PubMed

    Yang, Mingyuan; Yang, Changwei; Zhai, Xiao; Zhao, Jian; Zhu, Xiaodong; Li, Ming

    2017-02-15

    A retrospective study. To determine primary contributors to sagittal balance and establish a predictive equation of sagittal balance in normal asymptomatic subjects. Sagittal balance has been verified to be associated with health-related quality of life. Although many studies have been performed to explore factors contributing to sagittal balance in various disease states, no study has been conducted in normal asymptomatic subjects in East China. Medical records of 340 asymptomatic healthy volunteers were reviewed from January 2014 to August 2015, including 311 for exploring the risk factors and predictive equation, and 29 for validation. Demographic and radiological parameters were evaluated. Correlation analysis between spinopelvic parameters was pursued. Regression analyses were performed to establish predictive radiographic parameters for sagittal balance. Paired t test was conducted to test the regression equation. There was a very good correlation between T1 sagittal angle and maxTK, maxLL and SS, SS and PI, and PT and PI; a moderate correlation between maxTK and maxLL, and maxLL and PI; a weak correlation between T1 sagittal angle and age, age and maxTK, age and SS, age and PT, age and SVA, T1 sagittal angel and SVA, SVA and PT, and SVA and PI; and very weak correlation between T1 sagittal angle and maxLL, maxLL and PT, SVA and LL, and PT and SS. Age, T1 sagittal angle, maxLL, PT, and PI were primary contributors to sagittal balance, which could be predicted by the regression equation: SVA = 0.294 × age + 0.367 × T1 sagittal angle - 1.149 × maxLL-0.704 × PT + 1.378 × PI - 34.164. No significant difference was found between actual SVA and predicted SVA using our equation (P = 0.307). Age, T1 sagittal angle, maxLL, PT, and PI were primary contributors to maintaining sagittal balance in normal asymptomatic subjects, and sagittal balance could be predicted by calculation using the equation derived in this study. 2.

  5. A Colorectal Cancer Susceptibility New Variant at 4q26 in the Spanish Population Identified by Genome-Wide Association Analysis

    PubMed Central

    Real, Luis M.; Ruiz, Agustín; Gayán, Javier; González-Pérez, Antonio; Sáez, María E.; Ramírez-Lorca, Reposo; Morón, Francisco J.; Velasco, Juan; Marginet-Flinch, Ruth; Musulén, Eva; Carrasco, José M.; Moreno-Rey, Concha; Vázquez, Enrique; Chaves-Conde, Manuel; Moreno-Nogueira, Jose A.; Hidalgo-Pascual, Manuel; Ferrero-Herrero, Eduardo; Castellví-Bel, Sergi; Castells, Antoni; Fernandez-Rozadilla, Ceres; Ruiz-Ponte, Clara; Carracedo, Angel; González, Beatriz; Alonso, Sergio; Perucho, Manuel

    2014-01-01

    Background Non-hereditary colorectal cancer (CRC) is a complex disorder resulting from the combination of genetic and non-genetic factors. Genome–wide association studies (GWAS) are useful for identifying such genetic susceptibility factors. However, the single loci so far associated with CRC only represent a fraction of the genetic risk for CRC development in the general population. Therefore, many other genetic risk variants alone and in combination must still remain to be discovered. The aim of this work was to search for genetic risk factors for CRC, by performing single-locus and two-locus GWAS in the Spanish population. Results A total of 801 controls and 500 CRC cases were included in the discovery GWAS dataset. 77 single nucleotide polymorphisms (SNP)s from single-locus and 243 SNPs from two-locus association analyses were selected for replication in 423 additional CRC cases and 1382 controls. In the meta-analysis, one SNP, rs3987 at 4q26, reached GWAS significant p-value (p = 4.02×10−8), and one SNP pair, rs1100508 CG and rs8111948 AA, showed a trend for two-locus association (p = 4.35×10−11). Additionally, our GWAS confirmed the previously reported association with CRC of five SNPs located at 3q36.2 (rs10936599), 8q24 (rs10505477), 8q24.21(rs6983267), 11q13.4 (rs3824999) and 14q22.2 (rs4444235). Conclusions Our GWAS for CRC patients from Spain confirmed some previously reported associations for CRC and yielded a novel candidate risk SNP, located at 4q26. Epistasis analyses also yielded several novel candidate susceptibility pairs that need to be validated in independent analyses. PMID:24978480

  6. Strong association of 677 C>T substitution in the MTHFR gene with male infertility--a study on an indian population and a meta-analysis.

    PubMed

    Gupta, Nishi; Gupta, Saraswati; Dama, Madhukar; David, Archana; Khanna, Geeta; Khanna, Anil; Rajender, Singh

    2011-01-01

    Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate and methionine metabolism, making it crucial for DNA synthesis and methylation. The objective of this study was to analyze MTHFR gene 677C>T polymorphism in infertile male individuals from North India, followed by a meta-analysis on our data and published studies. We undertook genotyping on a total of 837 individuals including well characterized infertile (N = 522) and confirmed fertile (N = 315) individuals. The SNP was typed by direct DNA sequencing. Chi square test was done for statistical analysis. Published studies were searched using appropriate keywords. Source of data collection for meta-analysis included 'Pubmed', 'Ovid' and 'Google Scholar'. Those studies analyzing 677C>T polymorphism in male infertility and presenting all relevant data were included in meta-analysis. The genotype data for infertile subjects and fertile controls was extracted from each study. Chi square test was done to obtain odds ratio (OR) and p-value. Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2). The frequency of mutant (T) allele (p = 0.0025) and genotypes (CT+TT) (p = 0.0187) was significantly higher in infertile individuals in comparison to fertile controls in our case-control study. The overall summary estimate (OR) for allele and genotype meta-analysis were 1.304 (p = 0.000), 1.310 (p = 0.000), respectively, establishing significant association of 677C>T polymorphism with male infertility. 677C>T substitution associated strongly with male infertility in Indian population. Allele and genotype meta-analysis also supported its strong correlation with male infertility, thus establishing it as a risk factor.

  7. Strong Association of 677 C>T Substitution in the MTHFR Gene with Male Infertility - A Study on an Indian Population and a Meta-Analysis

    PubMed Central

    Gupta, Nishi; Gupta, Saraswati; Dama, Madhukar; David, Archana; Khanna, Geeta; Khanna, Anil; Rajender, Singh

    2011-01-01

    Background Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate and methionine metabolism, making it crucial for DNA synthesis and methylation. The objective of this study was to analyze MTHFR gene 677C>T polymorphism in infertile male individuals from North India, followed by a meta-analysis on our data and published studies. Methodology/Principal Findings We undertook genotyping on a total of 837 individuals including well characterized infertile (N = 522) and confirmed fertile (N = 315) individuals. The SNP was typed by direct DNA sequencing. Chi square test was done for statistical analysis. Published studies were searched using appropriate keywords. Source of data collection for meta-analysis included ‘Pubmed’, ‘Ovid’ and ‘Google Scholar’. Those studies analyzing 677C>T polymorphism in male infertility and presenting all relevant data were included in meta-analysis. The genotype data for infertile subjects and fertile controls was extracted from each study. Chi square test was done to obtain odds ratio (OR) and p-value. Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2). The frequency of mutant (T) allele (p = 0.0025) and genotypes (CT+TT) (p = 0.0187) was significantly higher in infertile individuals in comparison to fertile controls in our case-control study. The overall summary estimate (OR) for allele and genotype meta-analysis were 1.304 (p = 0.000), 1.310 (p = 0.000), respectively, establishing significant association of 677C>T polymorphism with male infertility. Conclusions/Significance 677C>T substitution associated strongly with male infertility in Indian population. Allele and genotype meta-analysis also supported its strong correlation with male infertility, thus establishing it as a risk factor. PMID:21799811

  8. Significant association between Let-7-KRAS rs712 G > T polymorphism and cancer risk in the Chinese population: a meta-analysis.

    PubMed

    Du, Xin-Ya; Hu, Yuan-Yuan; Xie, Chun; Deng, Chun-Yan; Liu, Cai-Yun; Luo, Zhi-Guo; Niu, Yu-Ming; Shen, Ming

    2017-01-16

    Association between let-7-KRAS rs712 polymorphism and cancer risk was inconsistent. We therefore conducted this meta-analysis to clarify the association between let-7-KRAS rs712 polymorphism and cancer risk with STATA 14.0 software. A systemic literature search in online databases (PubMed, Embase, CNKI and Wanfang database) was preformed to obtain relevant articles. A total of 13 case-control studies involving 3,453 patients and 4,470 controls were identified up to May 16, 2015. The pooled results indicated that significantly increased risk were observed in Chinese population in T vs. G (OR = 1.21, 95% CI = 1.03-1.42) and TT vs. GG + GT genetic models (OR = 1.69, 95% CI = 1.17-2.42). Sensitivity analysis was conducted and the result without heterogeneity showed significant associations in all five genetic models. Subgroup analyses of cancer type indicated a similar result in digestive cancer (for T vs. G: OR = 1.41, 95% CI = 1.26-1.57; GT vs. GG: OR = 1.24, 95% CI = 1.07-1.43; TT vs. GG: OR = 2.53, 95% CI = 1.86-3.44; GT + TT vs. GG: OR = 1.36, 95% CI = 1.19-1.56; TT vs. GG + GT: OR = 2.35, 95% CI = 1.73-3.19). In summary, these evidences demonstrate that let-7-KRAS rs712 G > T polymorphism might be associated with digestive system cancer risk in the Chinese population.

  9. QTL Analysis and Nested Association Mapping for Adult Plant Resistance to Powdery Mildew in Two Bread Wheat Populations

    PubMed Central

    Ren, Yan; Hou, Weixiu; Lan, Caixia; Basnet, Bhoja R.; Singh, Ravi P.; Zhu, Wei; Cheng, Xiyong; Cui, Dangqun; Chen, Feng

    2017-01-01

    CIMMYT wheat (Triticum aestivum L.) lines Francolin#1 and Quaiu#3 displayed effective and stable adult plant resistance (APR) to Chinese Blumeria graminis f. sp. tritici isolates in the field. To elucidate their genetic basis of resistance, two recombinant inbred line (RIL) populations of their crosses with Avocet, the susceptible parent, were phenotyped in Zhengzhou and Shangqiu in the 2014–2015 and 2015–2016 cropping seasons. These populations were also genotyped with SSR (simple sequence repeat markers) and DArT (diversity arrays technology) markers. Two common significant quantitative trait loci (QTL) on wheat chromosomes 1BL and 4BL were detected in both populations by joint and individual inclusive composite interval mapping, explaining 20.3–28.7% and 9.6–15.9% of the phenotypic variance in Avocet × Francolin#1 and 4.8–11.5% and 10.8–18.9% in Avocet × Quaiu#3, respectively. Additional QTL were mapped on chromosomes 1DL and 5BL in Avocet × Francolin#1 and on 2DL and 6BS in Avocet × Quaiu#3. Among these, QPm.heau-1DL is probably a novel APR gene contributing 6.1–8.5% of total phenotypic variance. The QTL on 1BL corresponds to the pleiotropic multi-pathogen resistance gene Yr29/Lr46/Pm39, whereas the QTL on 2DL maps to a similar region where stripe rust resistance gene Yr54 is located. The QTL identified can potentially be used for the improvement of powdery mildew and rust resistance in wheat breeding. PMID:28798752

  10. Systematic review and meta-analysis of the association between complement factor H I62V polymorphism and risk of polypoidal choroidal vasculopathy in Asian populations.

    PubMed

    Wang, Zhao-Yang; Zhao, Keke; Zheng, Jingwei; Rossmiller, Brian; Ildefonso, Cristhian; Biswal, Manas; Zhao, Pei-quan

    2014-01-01

    To investigate whether the polymorphism rs800292 (184G>A, I62V) in the complement factor H gene is associated with polypoidal choroidal vasculopathy (PCV) and the genetic difference between PCV and neovascular age-related macular degeneration (nAMD), in Asian populations. A comprehensive literature search was performed in PubMed, Medline, Web of Science, and reference lists. A system review and meta-analysis of the association between I62V and PCV and/or nAMD were performed from 8 studies involving 5,062 subjects. The following data from individual studies were extracted and analyzed: 1) comparison of I62V polymorphisms between PCV and controls; 2) comparison of I62V polymorphisms between PCV and nAMD. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed-effects models. The Q-statistic test was used to assess heterogeneity, and Egger's test was used to evaluate publication bias. Sensitivity analysis and cumulative meta-analysis were also performed. The I62V polymorphism showed a significant summary OR1 for genotype GA+GG versus homozygous genotype AA was 3.18 (95% CI, 2.51-4.04, P<0.00001), the OR2 of heterozygous genotype GA versus AA was 2.29 (95% CI: 1.79-2.94, P<0.00001), the OR3 of homozygous genotype GG versus AA was 4.42 (95% CI: 3.45-5.67, P<0.00001), and the OR4 of allele G versus A was 2.04 (95% CI: 1.85-2.26, P<0.00001). Sensitivity analysis indicated the robustness of our findings, and evidence of publication bias was not observed in our meta-analysis. Cumulative meta-analysis revealed that the summary ORs were stable. There was no significant difference in every genetic model between PCV and nAMD (n = 5, OR1 = 0.92, OR2 = 0.96, OR3 = 0.90, OR4 = 0.94). Our analysis provides evidence that the I62V polymorphism is associated with an increased risk of PCV. The variant of I62V could be a promising genetic biomarker of PCV in Asian populations.

  11. Lack of genetic associations between PPAR-γ gene rs1801282 polymorphism and Alzheimer's disease in general population: a meta-analysis.

    PubMed

    Wu, Yongfu; Wu, Qingyun; Zhang, Hanbin; Chen, Chuyan; Chen, Guangzhao; Yang, Huiling; Qin, Dongyun; Fu, Hui

    2015-06-01

    Published studies have evaluated the association between PPAR-γ rs1801282 polymorphism and Alzheimer's disease (AD) susceptibility. However, a definitive conclusion remains elusive. The aim of this study was to derive a more precise estimation of this association. We searched PubMed, Embase, Alzgene database, Chinese National Knowledge Infrastructure (CNKI), China Biological Medicine Database and Wanfang Databases for related studies. Twelve case-control studies with a total of 4874 cases and 5439 controls were finally identified to be eligible studies in this meta-analysis. The association was assessed by summarizing the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). Overall, there was no significant association between PPAR-γ rs1801282 polymorphism and Alzheimer's disease risk in all genetic models (the allele model G vs. C: OR=1.09, 95% CI 0.99-1.19, p=0.07; the homozygous model GG vs. CC: OR=1.04, 95% CI 0.75-1.44, p=0.80; heterozygote model GC vs. CC: OR=1.11, 95% CI 1,00-1.22, p=0.05; the dominant model GG+GC vs. CC: OR=1.10, 95% CI 1.00-1.22, p=0.05; the recessive model GG vs. GC+CC: OR=1.02, 95% CI 0.74-1.41, p=0.90). In subgroup analysis by ethnicity, no significant difference was found in both Asians and Caucasians. In summary, the present meta-analysis suggests that the PPAR-γ rs1801282 polymorphism may not be associated with genetic susceptibility of AD in general population. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Genetic analysis and identification of SSR markers associated with rice blast disease in a BC2F1 backcross population.

    PubMed

    Hasan, N; Rafii, M Y; Abdul Rahim, H; Nusaibah, S A; Mazlan, N; Abdullah, S

    2017-01-23

    Rice (Oryza sativa L.) blast disease is one of the most destructive rice diseases in the world. The fungal pathogen, Magnaporthe oryzae, is the causal agent of rice blast disease. Development of resistant cultivars is the most preferred method to achieve sustainable rice production. However, the effectiveness of resistant cultivars is hindered by the genetic plasticity of the pathogen genome. Therefore, information on genetic resistance and virulence stability are vital to increase our understanding of the molecular basis of blast disease resistance. The present study set out to elucidate the resistance pattern and identify potential simple sequence repeat markers linked with rice blast disease. A backcross population (BC2F1), derived from crossing MR264 and Pongsu Seribu 2 (PS2), was developed using marker-assisted backcross breeding. Twelve microsatellite markers carrying the blast resistance gene clearly demonstrated a polymorphic pattern between both parental lines. Among these, two markers, RM206 and RM5961, located on chromosome 11 exhibited the expected 1:1 testcross ratio in the BC2F1 population. The 195 BC2F1 plants inoculated against M. oryzae pathotype P7.2 showed a significantly different distribution in the backcrossed generation and followed Mendelian segregation based on a single-gene model. This indicates that blast resistance in PS2 is governed by a single dominant gene, which is linked to RM206 and RM5961 on chromosome 11. The findings presented in this study could be useful for future blast resistance studies in rice breeding programs.

  13. Association between edentulism and angina pectoris in Mexican adults aged 35 years and older: a multivariate analysis of a population-based survey.

    PubMed

    Medina-Solís, Carlo Eduardo; Pontigo-Loyola, América Patricia; Pérez-Campos, Eduardo; Hernández-Cruz, Pedro; Ávila-Burgos, Leticia; Kowolik, Michael J; Maupomé, Gerardo

    2014-03-01

    The possible association between oral infection and chronic inflammation and cardiovascular disease risk has been studied intensively. The present study is designed to determine the strength of association between edentulism and angina pectoris in Mexican adults aged 35 years and older. Using the tools and sampling strategies of the World Health Survey of the World Health Organization, cross-sectional data were collected in Mexico in the National Performance Assessment Survey (probabilistic, multistage, and cluster sampling). Dental information was available for 20 of the 32 states of Mexico. Angina and edentulism are self-reported in this study. Statistical analysis was performed using binary logistic regression adjusting for complex samples. A total of 13,966 participants, representing a population of 29,853,607 individuals, were included. Of the complete study population, 3,052,263 (10.2%) were completely toothless, and 673,810 (2.3%) were diagnosed with angina pectoris. After adjusting for smoking, alcohol consumption, diabetes, body mass index, and sex, the effect of edentulism on angina was modified by age (interaction), being more marked in the younger age group (odds ratio [OR] = exp(2.5597) =12.93) than in the older individuals surveyed (OR = exp(2.5597 + (-0.0334)) =12.51). Additionally, low physical activity (OR = 1.51; 95% confidence interval [CI] = 1.03 to 2.22) and higher socioeconomic status (OR = 1.37; 95% CI = 1.00 to 1.90) were more likely to be associated with angina pectoris. Overall, the results of this study, conducted in a representative sample of Mexican adults, suggest that an association exists between edentulism and angina pectoris. Additional studies are necessary to elucidate the underlying mechanism for this association.

  14. Associations of body mass index with cancer incidence among populations, genders, and menopausal status: A systematic review and meta-analysis.

    PubMed

    Wang, Jun; Yang, Dong-Lin; Chen, Zhong-Zhu; Gou, Ben-Fu

    2016-06-01

    In order to further reveal the differences of association between body mass index (BMI) and cancer incidence across populations, genders, and menopausal status, we performed comprehensive meta-analysis with eligible citations. The risk ratio (RR) of incidence at 10 different cancer sites (per 5kg/m(2) increase in BMI) were quantified separately by employing generalized least-squares to estimate trends, and combined by meta-analyses. We observed significantly stronger association between increased BMI and breast cancer incidence in the Asia-Pacific group (RR 1.18:1.11-1.26) than in European-Australian (1.05:1.00-1.09) and North-American group (1.06:1.03-1.08) (meta-regression p<0.05). No association between increased BMI and pancreatic cancer incidence (0.94:0.71-1.24) was shown in the Asia-Pacific group (meta-regression p<0.05), whereas positive associations were found in other two groups. A significantly higher RR in men was found for colorectal cancer in comparison with women (meta-regression p<0.05). Compared with postmenopausal women, premenopausal women displayed significantly higher RR for ovarian cancer (pre- vs. post-=1.10 vs. 1.01, meta-regression p<0.05), but lower RR for breast cancer (pre- vs. post-=0.99 vs. 1.11, meta-regression p<0.0001). Our results indicate that overweight or obesity is a strong risk factor of cancer incidence at several cancer sites. Genders, populations, and menopausal status are important factors effecting the association between obesity and cancer incidence for certain cancer types.

  15. Association between the IL1B -31C > T polymorphism and Helicobacter pylori infection in Asian and Latin American population: A meta-analysis.

    PubMed

    Sun, Xudong; Xu, Yuanyuan; Zhang, Fuhua; Jing, Tao; Han, Jian; Zhang, Jinhua

    2015-09-01

    Host genetic factors that control the production of cytokines, including interleukin-1β (IL-1β), possibly affect susceptibility to many Helicobacter pylori-related diseases. There is a complex interplay between H. pylori infection, the subsequent production of certain cytokines, and H. pylori-related diseases. We conducted a meta-analysis to clarify the association between the IL1B -31C > T polymorphism and H. pylori infection, and possible subsequent pathogenic mechanisms. Published literature contained within PubMed, Embase, and the Cochrane Library was used in our meta-analysis. Data were analyzed with the STATA 13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (95% CI). Egger's regression test, Begg's rank correlation test, and Begg's funnel plot were used to test publication bias. A total of 12 case-control studies comprising 5827 subjects (3335 cases and 2492 controls) were available for our meta-analysis. The IL1B -31C > T polymorphism was associated with an increased risk of H. pylori infection in Asian and Latin American population (TT + CT vs. CC, OR = 1.29, 95% CI = 1.14-1.46; TT vs. CT + CC, OR = 1.23, 95% CI = 1.09-1.39; TT vs. CC, OR = 1.43, 95% CI = 1.22-1.67; T allele vs. C allele, OR = 1.19, 95% CI = 1.10-1.29). A significant association was also found for all genetic models in various subgroups (cancer and no-cancer, hospital- and population-based). Our meta-analysis demonstrated that IL1B -31C > T polymorphism might increase H. pylori infection risk in Asian and Latin American population. Further studies with different ethnicities and larger sample size are required to validate this result. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Analysis of Intervention Strategies for Inhalation Exposure to Polycyclic Aromatic Hydrocarbons and Associated Lung Cancer Risk Based on a Monte Carlo Population Exposure Assessment Model

    PubMed Central

    Zhou, Bin; Zhao, Bin

    2014-01-01

    It is difficult to evaluate and compare interventions for reducing exposure to air pollutants, including polycyclic aromatic hydrocarbons (PAHs), a widely found air pollutant in both indoor and outdoor air. This study presents the first application of the Monte Carlo population exposure assessment model to quantify the effects of different intervention strategies on inhalation exposure to PAHs and the associated lung cancer risk. The method was applied to the population in Beijing, China, in the year 2006. Several intervention strategies were designed and studied, including atmospheric cleaning, smoking prohibition indoors, use of clean fuel for cooking, enhancing ventilation while cooking and use of indoor cleaners. Their performances were quantified by population attributable fraction (PAF) and potential impact fraction (PIF) of lung cancer risk, and the changes in indoor PAH concentrations and annual inhalation doses were also calculated and compared. The results showed that atmospheric cleaning and use of indoor cleaners were the two most effective interventions. The sensitivity analysis showed that several input parameters had major influence on the modeled PAH inhalation exposure and the rankings of different interventions. The ranking was reasonably robust for the remaining majority of parameters. The method itself can be extended to other pollutants and in different places. It enables the quantitative comparison of different intervention strategies and would benefit intervention design and relevant policy making. PMID:24416436

  17. Variance associated with the use of relative velocity for force platform gait analysis in a heterogeneous population of clinically normal dogs.

    PubMed

    Volstad, Nicola; Nemke, Brett; Muir, Peter

    2016-01-01

    Factors that contribute to variance in ground reaction forces (GRFs) include dog morphology, velocity, and trial repetition. Narrow velocity ranges are recommended to minimize variance. In a heterogeneous population, it may be preferable to minimize data variance and efficiently perform force platform gait analysis by evaluation of each individual dog at its preferred velocity, such that dogs are studied at a similar relative velocity (V*). Data from 27 normal dogs were obtained including withers and shoulder height. Each dog was trotted across a force platform at its preferred velocity, with controlled acceleration (±0.5 m/s(2)). V* ranges were created for withers and shoulder height. Variance effects from 12 trotting velocity ranges and associated V* ranges were examined using repeated-measures analysis-of-covariance. Mean bodyweight was 24.4 ± 7.4 kg. Individual dog, velocity, and V* significantly influenced GRF (P <0.001). Trial number significantly influenced thoracic limb peak vertical force (PVF) (P <0.001). Limb effects were not significant. The magnitude of variance effects was greatest for the dog effect. Withers height V* was associated with small GRF variance. Narrow velocity ranges typically captured a smaller percentage of trials and were not consistently associated with lower variance. The withers height V* range of 0.6-1.05 captured the largest proportion of trials (95.9 ± 5.9%) with no significant effects on PVF and vertical impulse. The use of individual velocity ranges derived from a withers height V* range of 0.6-1.05 will account for population heterogeneity while minimizing exacerbation of lameness in clinical trials studying lame dogs by efficient capture of valid trials.

  18. Revisiting genome wide association studies (GWAS) in coeliac disease: replication study in Spanish population and expression analysis of candidate genes.

    PubMed

    Plaza-Izurieta, Leticia; Castellanos-Rubio, Ainara; Irastorza, Iñaki; Fernández-Jimenez, Nora; Gutierrez, Galder; Bilbao, Jose Ramon

    2011-07-01

    Recent genome wide association studies (GWAS) on coeliac disease (CD) have identified risk loci harbouring genes that fit the accepted pathogenic model and are considered aetiological candidates. Using Taqman single nucleotide polymorphism (SNP) and expression assays, the study genotyped 11 SNPs tagging eight GWAS regions (1q31, 2q11-2q12, 3p21, 3q25-3q26, 3q28, 4q27, 6q25 and 12q24) in a Spanish cohort of 1094 CD patients and 540 controls, and performed expression analyses of candidate genes (RGS1, IL18R1/IL18RAP, CCR3, IL12A/SCHIP1, LPP, IL2/IL21-KIAA1109, TAGAP, and SH2B3) in intestinal mucosa from 29 CD children and eight controls. Polymorphisms in 1q31, 2q11-2q12, and 3q25 showed association in our cohort, and also 3q28 and 4q27 when combined with a previous study. Expression levels of IL12A, IL18RAP, IL21, KIAA1109, LPP, SCHIP1, and SH2B3 were affected by disease status, but the correlation between genotype and mRNA levels was observed only in IL12A, LPP, SCHIP1, and SH2B3. Expression differences between treated CD patients and controls along with SNP expression associations suggest a possible primary role for these four genes and their variants in pathogenesis. The lack of SNP effect in the remaining genes is probably a consequence of arbitrary candidate gene selection within association signals that are not based on functional studies.

  19. Multilevel analysis of the association between posterior restorations and gingival health in young adults: a population-based birth cohort.

    PubMed

    Demarco, Flávio Fernando; Correa, Marcos Britto; Horta, Bernardo; Barros, Aluísio J; Peres, Karen Glazer; Peres, Marco Aurélio

    2013-12-01

    To investigate the association of direct posterior restorations with gingival bleeding and dental calculus in young adults from a birth cohort. A representative sample (n = 720) of 5914 infants born live in Pelotas, Brazil, in 1982, were prospectively investigated, and posterior restorations and periodontal health outcomes assessed when they were 24 years of age. Tooth-level exploratory variables included the presence and number of restoration's surfaces. Demographic and socio-economic characteristics, oral health instructions, dental floss usage, dental caries presence and smoking were also considered whilst gingival bleeding and dental calculus were the outcomes. Multilevel logistic regression was carried out. Class I cavities were found in 15.2% (95% CI 14.5-15.9) of the teeth and class II in 3.6% (3.3-4.0). Percentage of teeth with gingival bleeding was 6.1% (5.6-6.6) and that with dental calculus 22% (21.2-22.8). Even after all the individual variables were controlled for, the presence of a class I [OR1.51 (1.14-2.00)] and class II [OR 1.76 (1.04-2.97)] cavities was positively associated with gingival bleeding. Class I [OR1.36 (1.13-1.65)] and Class II [OR1.80 (1.28-2.53)] cavities were associated with dental calculus also. Posterior restoration and higher number of restored surfaces was associated with a higher prevalence of gingival bleeding and dental calculus around the restoration. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. The ENPP1 K121Q polymorphism is associated with type 2 diabetes in European populations: evidence from an updated meta-analysis in 42,042 subjects.

    PubMed

    McAteer, Jarred B; Prudente, Sabrina; Bacci, Simonetta; Lyon, Helen N; Hirschhorn, Joel N; Trischitta, Vincenzo; Florez, Jose C

    2008-04-01

    Functional studies suggest that the nonsynonymous K121Q polymorphism in the ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) may confer susceptibility to insulin resistance; genetic evidence on its effect on type 2 diabetes, however, has been conflicting. We therefore conducted a new meta-analysis that includes novel unpublished data from the ENPP1 Consortium and recent negative findings from large association studies to address the contribution of K121Q to type 2 diabetes. After a systematic review of the literature, we evaluated the effect of ENPP1 K121Q on diabetes risk under three genetic models using a random-effects approach. Our primary analysis consisted of 30 studies comprising 15,801 case and 26,241 control subjects. Due to considerable heterogeneity and large differences in allele frequencies across populations, we limited our meta-analysis to those of self-reported European descent and, when available, included BMI as a covariate. We found a modest increase in risk of type 2 diabetes for QQ homozygotes in white populations (combined odds ratio [OR] 1.38 [95% CI 1.10-1.74], P = 0.005). There was no evidence of publication bias, but we noted significant residual heterogeneity among studies (P = 0.02). On meta-regression, 16% of the effect was accounted for by the mean BMI of control subjects. This association was stronger in studies in which control subjects were leaner but disappeared after adjustment for mean control BMI (combined OR 0.93 [95% CI 0.75-1.15], P = 0.50). The ENPP1 Q121 variant increases risk of type 2 diabetes under a recessive model of inheritance in whites, an effect that appears to be modulated by BMI.

  1. Analysis of the association between interleukin-1beta (+3954) gene polymorphism and chronic periodontitis in a sample of the south Indian population.

    PubMed

    Kaarthikeyan, Gurumoorthy; Jayakumar, Nadathur Doraisamy; Padmalatha, Ogoti; Sheeja, Varghese; Sankari, Malaippan; Anandan, Balakrisnan

    2009-01-01

    The aim of this study was to determine the association between IL-1B (+3954) gene polymorphism and chronic periodontitis in a sample of the south Indian population. This study employed a cross-sectional design involving individuals from the state of Tamil Nadu in the southern part of India. Genomic DNA was obtained from the white blood cells of 30 patients with chronic periodontitis (18 males and 12 females) and 31 healthy controls (20 males and 11 females). The age of the subjects ranged from 30 to 55 years old and all were non smokers. DNA was amplified using the polymerase chain reaction (PCR) with specific primers flanking the locus +3954 of IL-1beta gene and analyzed by 3% agarose gel electrophoresis. A Chi-square test was used to determine the genotype distribution between the groups and the relative risk was estimated with a 95% confidence interval. The chronic periodontitis group displayed a higher percentage of T allele, even though it was not statistically significant. The relative risk analysis between genotypes showed that the risk was higher for the CT genotype compared with the CC genotype and the risk was significant. In conclusion, our data suggested that there was no significant association between IL-1beta (+3954) gene polymorphism and chronic periodontitis in the south Indian population.

  2. Prediabetes Is Associated with HNF-4α P2 Promoter Polymorphism rs1884613: A Case-Control Study in Han Chinese Population and an Updated Meta-Analysis

    PubMed Central

    Wang, Changyi; Chen, Sihan; Zhang, Tao; Chen, Zhongwei; Liu, Shengyuan; Peng, Xiaolin; Ma, Jianping; Zhong, Xiaohong; Yan, Yanqiong; Tang, Linlin; Mai, Yifeng; Han, Liyuan

    2014-01-01

    Background. Controversy remains for the association between hepatocyte nuclear factor 4α (HNF-4α) P2 promoter polymorphism rs1884613 and type 2 diabetes (T2D). There was no association test of this polymorphism with prediabetes and T2D in the Chinese population. Moreover, an updated meta-analysis in various ethnic groups is needed to establish the contribution of rs1884613 to T2D risk. Methods. Using the Sequenom MassARRAY platform approach, we genotyped rs1884613 of HNF-4α in the P2 promoter region among 490 T2D patients, 471 individuals with prediabetes, and 575 healthy controls. All the individuals were recruited from 16 community health service centers in Nanshan district in Shenzhen province. Using STATA 11.0 software, meta-analysis was performed to summarize the overall contribution of rs1884613 to T2D risk. Results. Polymorphism rs1884613 was associated with genetic susceptibility to prediabetes in the whole samples (OR = 1.40, 95% CI = 1.16–1.68, P = 0.0001) and the female subgrouped samples (OR = 1.48, 95% CI = 1.14–1.92, P = 0.003) after adjusting for age and body mass index (BMI). In contrast, there was no association of rs1884613 with T2D in the whole samples and male in our case-control study and meta-analysis. Conclusions. Our results suggest that rs1884613 contributes to susceptibility to prediabetes, whereas this polymorphism may not play an important role in the development of T2D. PMID:25400315

  3. Analysis of Association between Norepinephrine Transporter Gene Polymorphisms and Personality Traits of NEO-FFI in a Japanese Population

    PubMed Central

    Narita, Shin; Nagahori, Kenta; Numajiri, Maki; Yoshihara, Eiji; Ohtani, Nobuyo; Ishigooka, Jun

    2015-01-01

    Objective Norepinephrine is an important chemical messenger that is involved in mood and stress in humans, and is reabsorbed by the norepinephrine transporter (NET). According to Cloninger's theory, the noradrenergic system mediates the personality trait of reward dependence. Thus far, although association studies on NET gene polymorphisms and Cloninger's personality traits have been reported, they yielded inconsistent results. Therefore, in the present study we investigated whether or not the 1287G/A, -182T/C and -3081A/T polymorphisms of the NET gene (SLC6A2) are associated with reward dependence-related traits, as assessed by the five-factor model. Methods After written informed consent was obtained from participants, the three NET gene polymorphisms were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), and personality was assessed by the Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) in 270 Japanese university students. Results A significant relation was found between the -3081A/T functional promoter polymorphism and NEO-FFI scores: those with the T allele exhibited a lower extraversion (E) score than those without the T allele (Mann-Whitney U-test: z=-3.861, p<0.001). However, there was no correlation between the other NET gene polymorphisms and E score, and no association with other dimensions and these three polymorphisms. Conclusion We conclude that the -3081A/T functional polymorphism in the NET gene may affect the extraversion of reward dependence-related traits, as measured by NEO-FFI. However, we used only the shortened version of NEO-PI-R in this study. Further investigations are necessary using the full version of self-rating personality questionnaires. PMID:26207133

  4. Small-for-Gestational-Age Births are Associated with Maternal Relationship Status: A Population-Wide Analysis.

    PubMed

    Steinberg, Jecca Rhea; Sanders, Lee; Cousens, Simon

    2016-08-01

    Objectives To examine the association between maternal relationship status during pregnancy and infant birth outcomes. Methods Observational study of the National Longitudinal Survey of Youth 1979, a nationally representative sample of 12,686 men and women between the ages of 14 and 21. We used data from surveys of women reporting childbirth between 1979 and 2004. Relationship status was defined as relationship with an opposite-sex partner in the child's birth year. Relationship stability was defined as the consistency in relationship status in the 1 year before, of, and after the child's birth. Childbirth outcome included small-for-gestational age (SGA) infant. We applied random effects logistic regression models to assess the association between relationship status and stability and childbirth outcome-adjusting for maternal race, infant sex, history of miscarriage, employment, maternal age, multiparity, cohort-entry year, household poverty status, and tobacco use. Results The study included 4439 women with 8348 live births. In fully adjusted models, term SGA infants were more commonly born to partnered women (AOR 1.81; 95 % CI 1.20-2.73) and unmarried women (AOR 1.82; CI 1.34-2.47; LRT p value 0.0001), compared to married women. SGA infants were also more commonly born in unstable relationships (AOR 1.72; 95 % CI 1.14-2.63; LRT p value 0.01) compared to stable relationships. Conclusions for Practice Maternal relationship status and stability during pregnancy is independently associated with risk of SGA infant birth.

  5. Analysis of the association between polymorphisms in the vitamin D receptor (VDR) gene and dental caries in a Chinese population.

    PubMed

    Hu, X P; Li, Z Q; Zhou, J Y; Yu, Z H; Zhang, J M; Guo, M L

    2015-09-28

    Environmental influences on the development and progression of dental caries are well known; however, there is little evidence of a genetic component imparting susceptibility to dental caries. The aim of this study was to investigate the relationship between a single nucleotide polymorphism in the vitamin D receptor TaqI locus and dental caries susceptibility in a Chinese population. This case-control study was conducted with a case group (264 patients with dental caries from northwestern China) and a control group (219 individuals without dental caries or systemic disease from the same area). DNA was extracted from the peripheral venous blood of the study participants; the distribution of TaqI locus genotypes and allele frequencies was determined via polymerase chain reaction-restriction fragment length polymorphism. The data obtained were statistically analyzed using the Hardy-Weinberg equilibrium and Chi-square test. The frequency of the Tt genotype in the case group (14.0%) was significantly higher than that in the control group (4.3%), as determined using the genotype TT as the reference. The risk of dental caries was increased 3.8-fold in individuals with the heterozygous Tt genotype compared to that in the individuals with the TT genotype. The proportion of the 't' allele in the case group (7.0%) and the control group (2.1%) was observed to be significantly different [P = 0.0003; OR = 3.592, confidence interval 95% (1.790-7.208)]. Our results therefore suggested that the allele 't' might be a genetic factor determining dental caries susceptibility in individuals from the northwest of China.

  6. Short-term population-based non-linear concentration-response associations between fine particulate matter and respiratory diseases in Taipei (Taiwan): a spatiotemporal analysis.

    PubMed

    Yu, Hwa-Lung; Chien, Lung-Chang

    2016-01-01

    Fine particulate matter <2.5 μm (PM2.5) has been associated with human health issues; however, findings regarding the influence of PM2.5 on respiratory disease remain inconsistent. The short-term, population-based association between the respiratory clinic visits of children and PM2.5 exposure levels were investigated by considering both the spatiotemporal distributions of ambient pollution and clinic visit data. We applied a spatiotemporal structured additive regression model to examine the concentration-response (C-R) association between children's respiratory clinic visits and PM2.5 concentrations. This analysis was separately performed on three respiratory disease categories that were selected from the Taiwanese National Health Insurance database, which includes 41 districts in the Taipei area of Taiwan from 2005 to 2007. The findings reveal a non-linear C-R pattern of PM2.5, particularly in acute respiratory infections. However, a PM2.5 increase at relatively lower levels can elevate the same-day respiratory health risks of both preschool children (<6 years old) and schoolchildren (6-14 years old). In preschool children, same-day health risks rise when concentrations increase from 0.76 to 7.44 μg/m(3), and in schoolchildren, same-day health risks rise when concentrations increase from 0.76 to 7.52 μg/m(3). Changes in PM2.5 levels generally exhibited no significant association with same-day respiratory risks, except in instances where PM2.5 levels are extremely high, and these occurrences do exhibit a significant positive influence on respiratory health that is especially notable in schoolchildren. A significant high relative rate of respiratory clinic visits are concentrated in highly populated areas. We highlight the non-linearity of the respiratory health effects of PM2.5 on children to investigate this population-based association. The C-R relationship in this study can provide a highly valuable alternative for assessing the effects of ambient air

  7. Risk of autism associated with general anesthesia during cesarean delivery: a population-based birth-cohort analysis.

    PubMed

    Chien, Li-Nien; Lin, Hsiu-Chen; Shao, Yu-Hsuan Joni; Chiou, Shu-Ti; Chiou, Hung-Yi

    2015-04-01

    The rates of Cesarean delivery (C-section) have risen to >30% in numerous countries. Increased risk of autism has been shown in neonates delivered by C-section. This study examined the incidence of autism in neonates delivered vaginally, by C-section with regional anesthesia (RA), and by C-section with general anesthesia (GA) to evaluate the risk of autism associated with C-section and obstetric anesthesia. During a mean follow-up of 4.3 years, the incidence of autism was higher in neonates delivered by C-section with GA than in neonates delivered vaginally, with an adjusted risk of 1.52 (95% confidence interval 1.18-1.94). However, the adjusted risk of autism in neonates delivered by C-section with RA and in neonates delivered vaginally was nonsignificantly different.

  8. Direct analysis of unphased SNP genotype data in population-based association studies via Bayesian partition modelling of haplotypes.

    PubMed

    Morris, Andrew P

    2005-09-01

    We describe a novel method for assessing the strength of disease association with single nucleotide polymorphisms (SNPs) in a candidate gene or small candidate region, and for estimating the corresponding haplotype relative risks of disease, using unphased genotype data directly. We begin by estimating the relative frequencies of haplotypes consistent with observed SNP genotypes. Under the Bayesian partition model, we specify cluster centres from this set of consistent SNP haplotypes. The remaining haplotypes are then assigned to the cluster with the "nearest" centre, where distance is defined in terms of SNP allele matches. Within a logistic regression modelling framework, each haplotype within a cluster is assigned the same disease risk, reducing the number of parameters required. Uncertainty in phase assignment is addressed by considering all possible haplotype configurations consistent with each unphased genotype, weighted in the logistic regression likelihood by their probabilities, calculated according to the estimated relative haplotype frequencies. We develop a Markov chain Monte Carlo algorithm to sample over the space of haplotype clusters and corresponding disease risks, allowing for covariates that might include environmental risk factors or polygenic effects. Application of the algorithm to SNP genotype data in an 890-kb region flanking the CYP2D6 gene illustrates that we can identify clusters of haplotypes with similar risk of poor drug metaboliser (PDM) phenotype, and can distinguish PDM cases carrying different high-risk variants. Further, the results of a detailed simulation study suggest that we can identify positive evidence of association for moderate relative disease risks with a sample of 1,000 cases and 1,000 controls.

  9. Association and interaction analysis of diabetes mellitus and SCN10A for cardiovascular autonomic neuropathy in a Chinese population.

    PubMed

    Lv, Yubao; Zhou, Linuo; Tang, Zihui; Dong, Jingcheng

    2017-06-01

    This study assessed the extent to which diabetes mellitus (DM) and SCN10A (rs7375036) and their interaction impact on cardiovascular autonomic neuropathy (CAN) susceptibility in a Chinese Han sample. We performed a study in a cross-sectional dataset that included 419 patients with DM and 1557 controls who were genotyped for the presence of the SCN10A rs7375036 polymorphisms. Genotyping was performed by iPLEX technology. The associations of rs7375036 and DM with CAN was assessed by using univariate and multivariate logistic regression controlling for confounders. The interaction between rs7375036 and DM for CAN susceptibility on an additive scale was calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). The univariate logistic analyses failed to show an association between the SCN10A rs7375036 polymorphisms and CAN. Interestingly, a novel interaction effect of SCN10A rs7375036 and DM on CAN was assessed (p=0.055; RERI=3.515, 95% CI 1.829 to 5.805; AP=0.632, 95% CI -0.368 to 1.632; S=4.361, 95% CI 2.071 to 9.184). Our findings suggest that there are interaction effects of DM and SCN10A (rs7375036) that influence the development of CAN. NCT02461342. 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/.

  10. The SNP rs402710 in 5p15.33 Is Associated with Lung Cancer Risk: A Replication Study in Chinese Population and a Meta-Analysis

    PubMed Central

    Zhu, Yaowu; Zou, Li; Li, Huijun; Zhu, Beibei; Xiong, Zhigang; Chen, Wei; Deng, Lingyan; Lou, Jiao; Wang, Xianxiu; Zhang, Yu; Wang, Zhenling; Miao, Xiaoping; Cheng, Liming

    2013-01-01

    Background Lung cancer is the most commonly diagnosed cancer and leading cause of cancer mortality in the world. A single nucleotide polymorphism (SNP), rs402710, located in 5p15.33, was firstly identified to be associated with the lung cancer risk in a genome-wide association study. However, some following replication studies yielded inconsistent results. Methodology and Findings A case-control study of 611 cases and 1062 controls in a Chinese population was conducted, and then a meta-analysis integrating the current and previously published studies with a total 31811 cases and 36333 controls was performed to explore the real effect of rs402710 on lung cancer susceptibility. Significant associations between the SNP rs402710 and lung cancer risk were observed in both case-control study and meta-analysis, with ORs equal to 0.77 (95%CI = 0.63–0.95) and 0.83 (95%CI = 0.81–0.86) in dominant model, respectively. By stratified analysis of our case-control study, the associations were also observed in never smoker group and non-small cell lung cancer(NSCLC) group with ORs equal to 0.71 (95%CI = 0.53–0.95) and 0.69 (95%CI = 0.55–0.87), which was remarkable that larger effect of the minor allele T was seen in the two groups than that in overall lung cancer. Besides, the sensitive and cumulative analysis indicated the robust stability of the current results of meta-analysis. Conclusion The results from our replication study and the meta-analysis provided firm evidence that rs402710 T allele significantly contributed to decreased lung cancer risk, and the case-control study implied that the variant may yield stronger effect on NSCLC and never smokers. However, the mechanism underlying the polymorphism conferring susceptibility to lung cancer is warranted to clarify in the follow-up studies. PMID:24194831

  11. [Association between CDH23 gene polymorphisms and susceptibility to noise-induced hearing loss in the Chinese population: a meta-analysis].

    PubMed

    Yu, J N; Wu, S S; He, C H; Zhang, C Y; Mu, H X; Ma, W S; Liu, B; Zhang, Y; Yu, S F

    2016-12-20

    Objective: To investigate the association between cadherin-23 (CDH23) gene polymorphisms and susceptibility to noise-induced hearing loss (NIHL) in the Chinese population through a meta-analysis. Methods: In June 2016, CNKI, VIP, Wanfang Data, and PubMed were searched for studies on the association between CDH23 gene polymorphisms and susceptibility to NIHL in the Chinese population. The articles were screened according to inclusion and exclusion criteria and related data were extracted. RevMan 5.3 was used for the meta-analysis. Results: A total of three Chinese articles were included. For CDH23-rs1227049, the risk of NIHL in people with C allele was 0.82 times (95%CI 0.39-1.73) that in people with G allele, the risk of NIHL in people with CG+CC genotype in the dominant model was 0.70 times (95%CI 0.34-1.43) that in people with GG genotype, the risk of NIHL in people with CC genotype in the recessive model was 1.23 times (95%CI 0.28-5.43) that in people with CG+GG genotype, and the risk of NIHL in people with CC genotype in the additive model was 1.05 times (95%CI 0.20-5.44) that in people with GG genotype (all P>0.05) . For CDH23-rs1227051, the risk of NIHL in people with T allele was 0.98 times (95%CI 0.71-1.37) that in people with C allele, and the risk of NIHL in people with CT+CC genotype in the dominant model was 1.09 times (95%CI 0.75-1.57) that in patients with TT genotype (both P>0.05) . Conclusion: There is still no enough evidence for the determination of CDH23-rs1227049 and CDH23-rs1227051 to be the susceptibility gene loci of NIHL.

  12. Population Structure, Diversity and Trait Association Analysis in Rice (Oryza sativa L.) Germplasm for Early Seedling Vigor (ESV) Using Trait Linked SSR Markers

    PubMed Central

    Anandan, Annamalai; Anumalla, Mahender; Pradhan, Sharat Kumar; Ali, Jauhar

    2016-01-01

    Early seedling vigor (ESV) is the essential trait for direct seeded rice to dominate and smother the weed growth. In this regard, 629 rice genotypes were studied for their morphological and physiological responses in the field under direct seeded aerobic situation on 14th, 28th and 56th days after sowing (DAS). It was determined that the early observations taken on 14th and 28th DAS were reliable estimators to study ESV as compared to56th DAS. Further, 96 were selected from 629 genotypes by principal component (PCA) and discriminate function analyses. The selected genotypes were subjected to decipher the pattern of genetic diversity in terms of both phenotypic and genotypic by using ESV QTL linked simple sequence repeat (SSR) markers. To assess the genetic structure, model and distance based approaches were used. Genotyping of 96 rice lines using 39 polymorphic SSRs produced a total of 128 alleles with the phenotypic information content (PIC) value of 0.24. The model based population structure approach grouped the accession into two distinct populations, whereas unrooted tree grouped the genotypes into three clusters. Both model based and structure based approach had clearly distinguished the early vigor genotypes from non-early vigor genotypes. Association analysis revealed that 16 and 10 SSRs showed significant association with ESV traits by general linear model (GLM) and mixed linear model (MLM) approaches respectively. Marker alleles on chromosome 2 were associated with shoot dry weight on 28 DAS, vigor index on 14 and 28 DAS. Improvement in the rate of seedling growth will be useful for identifying rice genotypes acquiescent to direct seeded conditions through marker-assisted selection. PMID:27031620

  13. Population Structure, Diversity and Trait Association Analysis in Rice (Oryza sativa L.) Germplasm for Early Seedling Vigor (ESV) Using Trait Linked SSR Markers.

    PubMed

    Anandan, Annamalai; Anumalla, Mahender; Pradhan, Sharat Kumar; Ali, Jauhar

    2016-01-01

    Early seedling vigor (ESV) is the essential trait for direct seeded rice to dominate and smother the weed growth. In this regard, 629 rice genotypes were studied for their morphological and physiological responses in the field under direct seeded aerobic situation on 14th, 28th and 56th days after sowing (DAS). It was determined that the early observations taken on 14th and 28th DAS were reliable estimators to study ESV as compared to 56th DAS. Further, 96 were selected from 629 genotypes by principal component (PCA) and discriminate function analyses. The selected genotypes were subjected to decipher the pattern of genetic diversity in terms of both phenotypic and genotypic by using ESV QTL linked simple sequence repeat (SSR) markers. To assess the genetic structure, model and distance based approaches were used. Genotyping of 96 rice lines using 39 polymorphic SSRs produced a total of 128 alleles with the phenotypic information content (PIC) value of 0.24. The model based population structure approach grouped the accession into two distinct populations, whereas unrooted tree grouped the genotypes into three clusters. Both model based and structure based approach had clearly distinguished the early vigor genotypes from non-early vigor genotypes. Association analysis revealed that 16 and 10 SSRs showed significant association with ESV traits by general linear model (GLM) and mixed linear model (MLM) approaches respectively. Marker alleles on chromosome 2 were associated with shoot dry weight on 28 DAS, vigor index on 14 and 28 DAS. Improvement in the rate of seedling growth will be useful for identifying rice genotypes acquiescent to direct seeded conditions through marker-assisted selection.

  14. Association of Grip Strength With Risk of All-Cause Mortality, Cardiovascular Diseases, and Cancer in Community-Dwelling Populations: A Meta-analysis of Prospective Cohort Studies.

    PubMed

    Wu, Yili; Wang, Weijing; Liu, Tianwei; Zhang, Dongfeng

    2017-06-01

    Grip strength has been linked to risk of adverse health outcomes. This study aimed to quantitatively assess the associations between grip strength and risk of all-cause mortality, cardiovascular diseases, and cancer in community-dwelling populations. A meta-analysis of prospective cohort studies was conducted. Embase, Medline, and PubMed were searched from inception to September 14, 2016. Study-specific most adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were combined with a random effects model. Dose-response relation was assessed by restricted cubic splines. Data were obtained from 42 studies including 3,002,203 participants. For lowest versus highest category of grip strength, the HRs (95% CIs) were 1.41 (1.30-1.52) for all-cause mortality, 1.63 (1.36-1.96) for cardiovascular diseases and 0.89 (0.66-1.20) for cancer. The HRs (95% CIs) with per-5-kg decrease in grip strength was 1.16 (1.12-1.20) for all-cause mortality, 1.21 (1.14-1.29) for cardiovascular diseases, 1.09 (1.05-1.14) for stroke, 1.07 (1.03-1.11) for coronary heart disease, and 1.01 (0.98-1.05) for cancer. The observed associations did not differ by sex, and remained after excluding participants with cardiovascular diseases or cancer at baseline. Adjustment for other covariates cannot fully explain the observed associations. Linear relationships were found between grip strength and risk of all-cause mortality and cardiovascular diseases within grip strength of 56 kg. Grip strength was an independent predictor of all-cause mortality and cardiovascular diseases in community-dwelling populations. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  15. 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

  16. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials

    PubMed Central

    Holmes, Michael V; Newcombe, Paul; Hubacek, Jaroslav A; Sofat, Reecha; Ricketts, Sally L; Cooper, Jackie; Breteler, Monique MB; Bautista, Leonelo E; Sharma, Pankaj; Whittaker, John C; Smeeth, Liam; Fowkes, F Gerald R; Algra, Ale; Shmeleva, Veronika; Szolnoki, Zoltan; Roest, Mark; Linnebank, Michael; Zacho, Jeppe; Nalls, Michael A; Singleton, Andrew B; Ferrucci, Luigi; Hardy, John; Worrall, Bradford B; Rich, Stephen S; Matarin, Mar; Norman, Paul E; Flicker, Leon; Almeida, Osvaldo P; van Bockxmeer, Frank M; Shimokata, Hiroshi; Khaw, Kay-Tee; Wareham, Nicholas J; Bobak, Martin; Sterne, Jonathan AC; Smith, George Davey; Talmud, Philippa J; van Duijn, Cornelia; Humphries, Steve E; Price, Jackie F; Ebrahim, Shah; Lawlor, Debbie A; Hankey, Graeme J; Meschia, James F; Sandhu, Manjinder S; Hingorani, Aroon D; Casas, Juan P

    2011-01-01

    Summary Background The MTHFR 677C→T polymorphism has been associated with raised homocysteine concentration and increased risk of stroke. A previous overview showed that the effects were greatest in regions with low dietary folate consumption, but differentiation between the effect of folate and small-study bias was difficult. A meta-analysis of randomised trials of homocysteine-lowering interventions showed no reduction in coronary heart disease events or stroke, but the trials were generally set in populations with high folate consumption. We aimed to reduce the effect of small-study bias and investigate whether folate status modifies the association between MTHFR 677C→T and stroke in a genetic analysis and meta-analysis of randomised controlled trials. Methods We established a collaboration of genetic studies consisting of 237 datasets including 59 995 individuals with data for homocysteine and 20 885 stroke events. We compared the genetic findings with a meta-analysis of 13 randomised trials of homocysteine-lowering treatments and stroke risk (45 549 individuals, 2314 stroke events, 269 transient ischaemic attacks). Findings The effect of the MTHFR 677C→T variant on homocysteine concentration was larger in low folate regions (Asia; difference between individuals with TT versus CC genotype, 3·12 μmol/L, 95% CI 2·23 to 4·01) than in areas with folate fortification (America, Australia, and New Zealand, high; 0·13 μmol/L, −0·85 to 1·11). The odds ratio (OR) for stroke was also higher in Asia (1·68, 95% CI 1·44 to 1·97) than in America, Australia, and New Zealand, high (1·03, 0·84 to 1·25). Most randomised trials took place in regions with high or increasing population folate concentrations. The summary relative risk (RR) of stroke in trials of homocysteine-lowering interventions (0·94, 95% CI 0·85 to 1·04) was similar to that predicted for the same extent of homocysteine reduction in large genetic studies in populations with similar

  17. Association of Change of Anthropometric Measurements With Incident Type 2 Diabetes Mellitus: A Pooled Analysis of the Prospective Population-Based CARLA and SHIP Cohort Studies.

    PubMed

    Hartwig, Saskia; Greiser, Karin Halina; Medenwald, Daniel; Tiller, Daniel; Herzog, Beatrice; Schipf, Sabine; Ittermann, Till; Völzke, Henry; Müller, Grit; Haerting, Johannes; Kluttig, Alexander

    2015-08-01

    Our objective was to investigate the association of change of anthropometric measurements and the incidence of type 2 diabetes mellitus (T2DM) within a pooled sample of 2 population-based cohorts.A final sample of 1324 women and 1278 men aged 31 to 83 years from 2 prospective cohorts in Germany, the CARLA (Cardiovascular Disease - Living and Ageing in Halle) and the SHIP study (Study of Health in Pomerania), were pooled. The association of change of body weight and waist circumference (WC) with incidence of T2DM was assessed by calculating sex-specific hazard ratios (HRs). We investigated the absolute change of markers of obesity as well as change relative to the baseline value and estimated crude and adjusted HRs. Furthermore, we conducted the analyses stratified by obesity status and age (<60 vs ≥60 years) at baseline.Associations were found for both change of body weight and WC and incidence of T2DM in the crude and adjusted analyses. In the stratified study sample, those participants with a body mass index of <30 kg/m at baseline showed considerably lower HRs compared with obese women and men for both weight and WC. In the age-stratified analysis, we still found associations between change of weight and WC and incident T2DM with only marginal differences between the age groups.Our study showed associations of change of weight and WC as markers of obesity with incidence of T2DM. Keeping a healthy and primarily stable weight should be the goal for preventing the development of T2DM.

  18. Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts.

    PubMed

    van der Velde, Marije; Matsushita, Kunihiro; Coresh, Josef; Astor, Brad C; Woodward, Mark; Levey, Andrew; de Jong, Paul; Gansevoort, Ron T; van der Velde, Marije; Matsushita, Kunihiro; Coresh, Josef; Astor, Brad C; Woodward, Mark; Levey, Andrew S; de Jong, Paul E; Gansevoort, Ron T; Levey, Andrew; El-Nahas, Meguid; Eckardt, Kai-Uwe; Kasiske, Bertram L; Ninomiya, Toshiharu; Chalmers, John; Macmahon, Stephen; Tonelli, Marcello; Hemmelgarn, Brenda; Sacks, Frank; Curhan, Gary; Collins, Allan J; Li, Suying; Chen, Shu-Cheng; Hawaii Cohort, K P; Lee, Brian J; Ishani, Areef; Neaton, James; Svendsen, Ken; Mann, Johannes F E; Yusuf, Salim; Teo, Koon K; Gao, Peggy; Nelson, Robert G; Knowler, William C; Bilo, Henk J; Joosten, Hanneke; Kleefstra, Nanno; Groenier, K H; Auguste, Priscilla; Veldhuis, Kasper; Wang, Yaping; Camarata, Laura; Thomas, Beverly; Manley, Tom

    2011-06-01

    Screening for chronic kidney disease is recommended in people at high risk, but data on the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with all-cause and cardiovascular mortality are limited. To clarify this, we performed a collaborative meta-analysis of 10 cohorts with 266,975 patients selected because of increased risk for chronic kidney disease, defined as a history of hypertension, diabetes, or cardiovascular disease. Risk for all-cause mortality was not associated with eGFR between 60-105 ml/min per 1.73 m², but increased at lower levels. Hazard ratios at eGFRs of 60, 45, and 15 ml/min per 1.73 m² were 1.03, 1.38 and 3.11, respectively, compared to an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log risk for all-cause mortality without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 10, 30 and 300 mg/g were 1.08, 1.38, and 2.16, respectively compared to a ratio of five. Albuminuria and eGFR were multiplicatively associated with all-cause mortality, without evidence for interaction. Similar associations were observed for cardiovascular mortality. Findings in cohorts with dipstick data were generally comparable to those in cohorts measuring albumin-to-creatinine ratios. Thus, lower eGFR and higher albuminuria are risk factors for all-cause and cardiovascular mortality in high-risk populations, independent of each other and of cardiovascular risk factors.

  19. Analysis of Grapevine rupestris stem pitting-associated virus in Slovakia Reveals Differences in Intra-Host Population Diversity and Naturally Occurring Recombination Events.

    PubMed

    Glasa, Miroslav; Predajňa, Lukáš; Šoltys, Katarína; Sihelská, Nina; Nagyová, Alžbeta; Wetzel, Thierry; Sabanadzovic, Sead

    2017-02-01

    Grapevine rupestris stem pitting-associated virus (GRSPaV) is a worldwide-distributed pathogen in grapevines with a high genetic variability. Our study revealed differences in the complexity of GRSPaV population in a single host. A single-variant GRSPaV infection was detected from the SK30 grapevine plant. On the contrary, SK704 grapevine was infected by three different GRSPaV variants. Variant-specific RT-PCR detection protocols have been developed in this work to study distribution of the three different variants in the same plant during the season. This study showed their randomized distribution in the infected SK704 grapevine plant. Comparative analysis of fulllength genome sequences of four Slovak GRSPaV isolates determined in this work and 14 database sequences showed that population of the virus cluster into four major phylogenetic lineages. Moreover, our analyses suggest that genetic recombination along with point mutations could play a significant role in shaping evolutionary history of GRSPaV and contributed to its extant genetic diversification.

  20. Analysis of Grapevine rupestris stem pitting-associated virus in Slovakia Reveals Differences in Intra-Host Population Diversity and Naturally Occurring Recombination Events

    PubMed Central

    Glasa, Miroslav; Predajňa, Lukáš; Šoltys, Katarína; Sihelská, Nina; Nagyová, Alžbeta; Wetzel, Thierry; Sabanadzovic, Sead

    2017-01-01

    Grapevine rupestris stem pitting-associated virus (GRSPaV) is a worldwide-distributed pathogen in grapevines with a high genetic variability. Our study revealed differences in the complexity of GRSPaV population in a single host. A single-variant GRSPaV infection was detected from the SK30 grapevine plant. On the contrary, SK704 grapevine was infected by three different GRSPaV variants. Variant-specific RT-PCR detection protocols have been developed in this work to study distribution of the three different variants in the same plant during the season. This study showed their randomized distribution in the infected SK704 grapevine plant. Comparative analysis of fulllength genome sequences of four Slovak GRSPaV isolates determined in this work and 14 database sequences showed that population of the virus cluster into four major phylogenetic lineages. Moreover, our analyses suggest that genetic recombination along with point mutations could play a significant role in shaping evolutionary history of GRSPaV and contributed to its extant genetic diversification. PMID:28167886

  1. A positive association between anxiety disorders and cannabis use or cannabis use disorders in the general population- a meta-analysis of 31 studies

    PubMed Central

    2014-01-01

    Background The aim of the current study was to investigate the association between anxiety and cannabis use/cannabis use disorders in the general population. Methods A total of N = 267 studies were identified from a systematic literature search (any time- March 2013) of Medline and PsycInfo databases, and a hand search. The results of 31 studies (with prospective cohort or cross-sectional designs using non-institutionalised cases) were analysed using a random-effects meta-analysis with the inverse variance weights. Lifetime or past 12-month cannabis use, anxiety symptoms, and cannabis use disorders (CUD; dependence and/or abuse/harmful use) were classified according to DSM/ICD criteria or scores on standardised scales. Results There was a small positive association between anxiety and either cannabis use (OR = 1.24, 95% CI: 1.06-1.45, p = .006; N = 15 studies) or CUD (OR = 1.68, 95% CI: 1.23-2.31, p = .001; N = 13 studies), and between comorbid anxiety + depression and cannabis use (OR = 1.68, 95% CI: 1.17-2.40, p = .004; N = 5 studies). The positive associations between anxiety and cannabis use (or CUD) were present in subgroups of studies with ORs adjusted for possible confounders (substance use, psychiatric illness, demographics) and in studies with clinical diagnoses of anxiety. Cannabis use at baseline was significantly associated with anxiety at follow-up in N = 5 studies adjusted for confounders (OR = 1.28, 95% CI: 1.06-1.54, p = .01). The opposite relationship was investigated in only one study. There was little evidence for publication bias. Conclusion Anxiety is positively associated with cannabis use or CUD in cohorts drawn from some 112,000 non-institutionalised members of the general population of 10 countries. PMID:24884989

  2. Association between population prevalence of smoking and incidence of meningococcal disease in Norway, Sweden, Denmark and the Netherlands between 1975 and 2009: a population-based time series analysis

    PubMed Central

    Norheim, Gunnstein; Sadarangani, Manish; Omar, Omar; Yu, Ly-Mee; Mølbak, Kåre; Howitz, Michael; Olcén, Per; Haglund, Margaretha; van der Ende, Arie; Pollard, Andrew J

    2014-01-01

    Objective To investigate the relationship between the prevalence of smoking in the population and incidence of invasive meningococcal disease (IMD) among children under 5 years of age. Design Retrospective, longitudinal, observational study. Poisson regression controlled for confounding factors. Setting Norway, Sweden, Denmark and the Netherlands between 1975 and 2009. Population Total population of approximately 35 million people in these four countries. Data sources Data were collected from the Ministries of Health, National Statistics Bureaus and other relevant national institutes. Results In Norway, there was a significant positive relationship between the annual prevalence of daily smokers among individuals aged 25–49 years and the incidence of IMD in children under 5 years of age, unadjusted (RR=1.04–1.06, 95% CI 1.02 to 1.07, p<0.001) and after adjustment for time of year (quarter), incidence of influenza-like illness and household crowding (RR=1.05–1.07, 95% CI 1.03 to 1.09, p<0.001). Depending on age group, the risk of IMD increased by 5.2–6.9% per 1% increase in smoking prevalence among individuals aged 25–49 years in adjusted analyses. Using limited datasets from the three other countries, unadjusted analysis showed positive associations between IMD in children related to older smokers in Sweden and the Netherlands and negative associations related to younger smokers in Sweden. However, there were no demonstrable associations between incidence of IMD and prevalence of smoking, after adjustment for the same confounding variables. Conclusions The reduced incidence of IMD in Norway between 1975 and 2009 may partly be explained by the reduced prevalence of smoking during this period. High-quality surveillance data are required to confirm this in other countries. Strong efforts to reduce smoking in the whole population including targeted campaigns to reduce smoking among adults may have a role to play in the prevention of IMD in children

  3. An inverse association of body mass index and prostate-specific antigen in northwest men of China: a population-based analysis.

    PubMed

    Zhang, Jianqin; Sheng, Binwu; Ma, Mao; Nan, Xunyi

    2015-01-01

    To examine the relationship between body mass index (BMI) and prostate-specific antigen (PSA) in Chinese men and to investigate whether this relationship was independent of other factors. Cross-sectional analysis was in men aged 19 to 82 years old (N=12,964) who without prostate cancer and had health examination between 2008 and 2013 in a clinical center in Xi'an, China. Obesity and overweight were classified according to the WHO criterion. Mean PSA level was calculated by categories (normal weight, overweight, and obesity) and age group (≤ 40, 41-59, ≥ 60 years old). The association between BMI and PSA was examined using multivariate regression models and stratified by age. The crude prevalence was 38.42% for overweight and 3.47% for obesity in the study population. Mean PSA level increased with age at each BMI category. BMI was negatively associated with PSA level at each age group, independent of fasting plasma glucose (FPG) and prostate volume. Per unit increase in BMI was associated with a decrease of PSA by 0.03 (P=0.05), 0.11(P < 0.001), and 0.15 (P < 0.001) in men aged ≤ 40, between 41 to 59, and > 60 years old, respectively. Our results indicate that a higher BMI is associated with a lower level of PSA in healthy Chinese men across all age group, independent of prostate volume and FPG. With the current obesity epidemic, individual's BMI should be considered when PSA test is used to screen or diagnose prostate cancer.

  4. Analysis of single nucleotide polymorphisms and haplotypes in the neuropeptide Y gene: no evidence for association with alcoholism in a German population sample.

    PubMed

    Zill, Peter; Preuss, Ulrich W; Koller, Gabrielle; Bondy, Brigitta; Soyka, Michael

    2008-03-01

    Several lines of evidence from animal and electrophysiological studies indicate that the neuropeptide Y (NPY) gene is involved in the pathophysiology of alcohol dependence. Recent studies have provided evidence for an association between a Leu7Pro polymorphism, as well as 2 promoter single nucleotide polymorphisms (SNPs) in the NPY gene (G-602T, T-399C) and alcohol dependence. The aim of the present study was to analyze these variants in a large sample of the Munich Gene Bank of Alcoholism. We performed single SNP and haplotype studies in 465 alcohol dependent patients and 448 healthy controls with 3 SNPs in the promoter region (-883ins/del, G-602T, T-399C) and the Leu7Pro polymorphism in exon 2 of the NPY gene. Neither single SNP-, nor haplotype analysis could detect significant associations with alcohol dependence. Additionally we could not detect any relation to Cloninger's Type 1/2 or Babor's Type A/B classification, to withdrawal symptoms, to the age of onset or to the amount of alcohol intake. In conclusion, our results suggest that the analyzed SNPs, as well as the corresponding haplotypes of the NPY gene are unlikely to play a major role in the pathophysiology of alcohol dependence in the investigated sample from the German population. Further analyses are needed to confirm the present results.

  5. Association of AGT M235T and ACE I/D polymorphisms with the risk of ischemic stroke: meta-analysis in Han Chinese population.

    PubMed

    Wang, Bin; Guo, Qingqing; Peng, Yaguang; Lu, Jiapeng; Singh, Balwinder; Hua, Baojin

    2012-09-15

    Angiotensinogen (AGT) M235T and angiotensin-converting enzyme (ACE) Insertion/Deletion polymorphisms have been reported to be significantly associated with ischemic stroke. However, the results have been inconsistent. Therefore, we performed a comprehensive meta-analysis to evaluate the role of the AGT M235T and ACE I/D polymorphisms as risk factors for ischemic stroke in Han Chinese population. We performed a comprehensive search in MEDLINE (PubMed), the China National Knowledge Infrastructure (CNKI) platforms and WANFANG databases, to identify the studies evaluating the association between the AGT M235T or ACE I/D polymorphisms and ischemic stroke, up to August 2011, in Chinese and English languages. The combined effects were estimated by fixed effects model or random effects model depending on the between-study heterogeneity, which was analyzed using the heterogeneity Q statistic test. Publication bias was evaluated using Begg's test, Egger's test and funnel plot. A total of 58 studies were selected for the final meta-analysis, including 7168 ischemic stroke cases and 5944 controls. Among them, 11 studies evaluated the effect of AGT M235T as a risk factor for ischemic stroke, while the remaining evaluated the ACE I/D polymorphism. Overall, a significant association was identified for both the AGT M235T and ACE I/D polymorphisms, under pair wise comparisons, dominant, recessive and additive models, however, there was significant heterogeneity among the ACE I/D polymorphism studies (P<0.10). On meta-regression analyses, geographic region was identified as a significant source of between-study heterogeneity for both the polymorphisms. The stratified analysis by geographic distribution indicated that the AGT T allele could increase the risk of ischemic stroke in northern Chinese (OR=2.029, 95% CI: 1.714-2.401, P<0.001) as compared to southern Chinese individuals (OR=1.821, 95% CI: 1.586-2.090, P=0.002). In contrast, the ACE D allele could increase the susceptibility

  6. Sex is a moderator of the association between NOS1AP sequence variants and QTc in two long QT syndrome founder populations: a pedigree-based measured genotype association analysis.

    PubMed

    Winbo, Annika; Stattin, Eva-Lena; Westin, Ida Maria; Norberg, Anna; Persson, Johan; Jensen, Steen M; Rydberg, Annika

    2017-07-18

    Sequence variants in the NOS1AP gene have repeatedly been reported to influence QTc, albeit with moderate effect sizes. In the long QT syndrome (LQTS), this may contribute to the substantial QTc variance seen among carriers of identical pathogenic sequence variants. Here we assess three non-coding NOS1AP sequence variants, chosen for their previously reported strong association with QTc in normal and LQTS populations, for association with QTc in two Swedish LQT1 founder populations. This study included 312 individuals (58% females) from two LQT1 founder populations, whereof 227 genotype positive segregating either Y111C (n = 148) or R518* (n = 79) pathogenic sequence variants in the KCNQ1 gene, and 85 genotype negatives. All were genotyped for NOS1AP sequence variants rs12143842, rs16847548 and rs4657139, and tested for association with QTc length (effect size presented as mean difference between derived and wildtype, in ms), using a pedigree-based measured genotype association analysis. Mean QTc was obtained by repeated manual measurement (preferably in lead II) by one observer using coded 50 mm/s standard 12-lead ECGs. A substantial variance in mean QTc was seen in genotype positives 476 ± 36 ms (Y111C 483 ± 34 ms; R518* 462 ± 34 ms) and genotype negatives 433 ± 24 ms. Female sex was significantly associated with QTc prolongation in all genotype groups (p < 0.001). In a multivariable analysis including the entire study population and adjusted for KCNQ1 genotype, sex and age, NOS1AP sequence variants rs12143842 and rs16847548 (but not rs4657139) were significantly associated with QT prolongation, +18 ms (p = 0.0007) and +17 ms (p = 0.006), respectively. Significant sex-interactions were detected for both sequent variants (interaction term r = 0.892, p < 0.001 and r = 0.944, p < 0.001, respectively). Notably, across the genotype groups, when stratified by sex neither rs12143842 nor rs16847548 were significantly associated with

  7. Population-based case-control association studies.

    PubMed

    Hancock, Dana B; Scott, William K

    2012-07-01

    This unit provides an overview of the design and analysis of population-based case-control studies of genetic risk factors for complex disease. Considerations specific to genetic studies are emphasized. The unit reviews basic study designs differentiating case-control studies from others, presents different genetic association strategies (candidate gene, genome-wide association, and high-throughput sequencing), introduces basic methods of statistical analysis for case-control data and approaches to combining case-control studies, and discusses measures of association and impact. Admixed populations, controlling for confounding (including population stratification), consideration of multiple loci and environmental risk factors, and complementary analyses of haplotypes, genes, and pathways are briefly discussed. Readers are referred to basic texts on epidemiology for more details on general conduct of case-control studies.

  8. Association of the triglycerides to high-density lipoprotein cholesterol ratio with the risk of chronic kidney disease: analysis in a large Japanese population.

    PubMed

    Tsuruya, Kazuhiko; Yoshida, Hisako; Nagata, Masaharu; Kitazono, Takanari; Hirakata, Hideki; Iseki, Kunitoshi; Moriyama, Toshiki; Yamagata, Kunihiro; Yoshida, Hideaki; Fujimoto, Shouichi; Asahi, Koichi; Kurahashi, Issei; Ohashi, Yasuo; Watanabe, Tsuyoshi

    2014-03-01

    To investigate the relationship between triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-C) and chronic kidney disease (CKD). We used data from 216,007 Japanese adults who participated in a nationwide health checkup program. Men (n = 88,516) and women (n = 127,491) were grouped into quartiles based on their TG/HDL-C levels (<1.26, 1.26-1.98, 1.99-3.18, and >3.18 in men; <0.96, 0.96-1.44, 1.45-2.22, and >2.22 in women). We cross-sectionally assessed the association of TG/HDL-C levels with CKD [defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m(2) (low eGFR) and/or proteinuria (defined as urinary protein ≥ 1+ on dipstick testing)], low eGFR, and proteinuria. The prevalence of CKD, low eGFR, and proteinuria increased significantly with elevating quartiles of TG/HDL-C in both genders (all P for trend <0.001). Participants in the highest quartile of TG/HDL-C had a significantly greater risk of CKD than those in the lowest quartile after adjustment for the relevant confounding factors (odds ratio: 1.57, 95% confidence interval: 1.49-1.65 in men; 1.41, 1.34-1.48 in women, respectively). Furthermore, there were significant associations with low eGFR and proteinuria. In stratified analysis, the risk of CKD increased linearly with greater TG/HDL-C levels in participants with and without hypertension, diabetes, and obesity. Moreover, higher TG/HDL-C levels were relevant for CKD, especially in participants with hypertension and diabetes (P for interaction <0.001, respectively). An elevated TG/HDL-C is associated with the risk of CKD in the Japanese population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Next generation semiconductor based sequencing of bitter taste receptor genes in different pig populations and association analysis using a selective DNA pool-seq approach.

    PubMed

    Ribani, A; Bertolini, F; Schiavo, G; Scotti, E; Utzeri, V J; Dall'Olio, S; Trevisi, P; Bosi, P; Fontanesi, L

    2017-02-01

    Taste perception in animals affects feed intake and may influence production traits. In particular, bitter is sensed by receptors encoded by the family of TAS2R genes. In this research, using a DNA pool-seq approach coupled with next generation semiconductor based target resequencing, we analysed nine porcine TAS2R genes (TAS2R1, TAS2R3, TAS2R4, TAS2R7, TAS2R9, TAS2R10, TAS2R16, TAS2R38 and TAS2R39) to identify variability and, at the same time, estimate single nucleotide polymorphism (SNP) allele frequencies in several populations and testing differences in an association analysis. Equimolar DNA pools were prepared for five pig breeds (Italian Duroc, Italian Landrace, Pietrain, Meishan and Casertana) and wild boars (5-10 individuals each) and for two groups of Italian Large White pigs with extreme and divergent back fat thickness (50 + 50 pigs). About 1.8 million reads were obtained by sequencing amplicons generated from these pools. A total of 125 SNPs were identified, of which 37 were missense mutations. Three of them (p.Ile53Phe and p.Trp85Leu in TAS2R4; p.Leu37Ser in TAS2R39) could have important effects on the function of these bitter taste receptors, based on in silico predictions. Variability in wild boars seems lower than that in domestic breeds potentially as a result of selective pressure in the wild towards defensive bitter taste perception. Three SNPs in TAS2R38 and TAS2R39 were significantly associated with back fat thickness. These results may be important to understand the complexity of taste perception and their associated effects that could be useful to develop nutrigenetic approaches in pig breeding and nutrition. © 2016 Stichting International Foundation for Animal Genetics.

  10. Associations of pregnancy-associated plasma protein-A level with essential hypertension and hypertensive disorders in pregnancy in Chinese population: a meta-analysis of 20 research studies involving 3332 individuals

    PubMed Central

    Cai, Gaojun; Zhang, Bifeng; Weng, Weijin; Yang, Liping; Shi, Ganwei; Xue, Sheliang; Fu, Xingli

    2015-01-01

    Objective To explore the associations between serum pregnancy-associated plasma protein-A (PAPP-A) level, and essential hypertension (EH) and hypertensive disorders in pregnancy (HDP) in Chinese population. Methods Pertinent studies were independently searched in PubMed, Embase, Cochrane Library, Chinese Biomedical Database (CBM), Wanfang databases and China National Knowledge Infrastructure (CNKI). The standardised mean difference (SMD) with 95% CIs was used to estimate the size of the effect. The subgroup analyses and meta-regression analysis were performed to identify the sources of heterogeneity among studies. Sensitivity analysis was conducted to assess the stability of the results. The publication bias between studies was examined by using Begg's funnel plots and Egger's test. Results A total of 20 studies involving 1493 patients and 1839 controls were included in the current meta-analysis. The PAPP-A level was significantly higher in EH patients than in controls (SMD=1.960, 95% CI 1.305 to 2.615, p<0.001), and significant associations were observed in all subgroups. The PAPP-A level was also significantly higher in HDP patients than in healthy pregnant women (SMD=2.249; 95% CI 1.324 to 3.173, p<0.001). The positive association between PAPP-A level and the risk of HDP was consistently observed in all subgroups except the subgroup with low NOS score. Conclusions The present meta-analysis suggests that an elevated PAPP-A level may be associated with susceptibilities to EH and HDP. PMID:26416511

  11. Associations of pregnancy-associated plasma protein-A level with essential hypertension and hypertensive disorders in pregnancy in Chinese population: a meta-analysis of 20 research studies involving 3332 individuals.

    PubMed

    Cai, Gaojun; Zhang, Bifeng; Weng, Weijin; Yang, Liping; Shi, Ganwei; Xue, Sheliang; Fu, Xingli

    2015-09-28

    To explore the associations between serum pregnancy-associated plasma protein-A (PAPP-A) level, and essential hypertension (EH) and hypertensive disorders in pregnancy (HDP) in Chinese population. Pertinent studies were independently searched in PubMed, Embase, Cochrane Library, Chinese Biomedical Database (CBM), Wanfang databases and China National Knowledge Infrastructure (CNKI). The standardised mean difference (SMD) with 95% CIs was used to estimate the size of the effect. The subgroup analyses and meta-regression analysis were performed to identify the sources of heterogeneity among studies. Sensitivity analysis was conducted to assess the stability of the results. The publication bias between studies was examined by using Begg's funnel plots and Egger's test. A total of 20 studies involving 1493 patients and 1839 controls were included in the current meta-analysis. The PAPP-A level was significantly higher in EH patients than in controls (SMD=1.960, 95% CI 1.305 to 2.615, p<0.001), and significant associations were observed in all subgroups. The PAPP-A level was also significantly higher in HDP patients than in healthy pregnant women (SMD=2.249; 95% CI 1.324 to 3.173, p<0.001). The positive association between PAPP-A level and the risk of HDP was consistently observed in all subgroups except the subgroup with low NOS score. The present meta-analysis suggests that an elevated PAPP-A level may be associated with susceptibilities to EH and HDP. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. Association of Dietary Vitamin K1 Intake With the Incidence of Cataract Surgery in an Adult Mediterranean Population: A Secondary Analysis of a Randomized Clinical Trial.

    PubMed

    Camacho-Barcia, María L; Bulló, Mònica; Garcia-Gavilán, Jesús F; Ruiz-Canela, Miguel; Corella, Dolores; Estruch, Ramón; Fitó, Montserrat; García-Layana, Alfredo; Arós, Fernando; Fiol, Miquel; Lapetra, José; Serra-Majem, Lluis; Pintó, Xavier; García-Arellano, Ana; Vinyoles, Ernest; Sorli, José Vicente; Salas-Salvadó, Jordi

    2017-06-01

    Cataract, one of the most frequent causes of blindness in developed countries, is strongly associated with aging. The exact mechanisms underlying cataract formation are still unclear, but growing evidence suggests a potential role of inflammatory and oxidative processes. Therefore, antioxidant and anti-inflammatory factors of the diet, such as vitamin K1, could play a protective role. To examine the association between dietary vitamin K1 intake and the risk of incident cataracts in an elderly Mediterranean population. A prospective analysis was conducted in 5860 participants from the Prevención con Dieta Mediterránea Study, a randomized clinical trial executed between 2003 and 2011. Participants were community-dwelling men (44.2%) and women (55.8%), and the mean (SD) age was 66.3 (6.1) years. Dietary vitamin K1 intake was evaluated using a validated food frequency questionnaire. The time to the cataract event was calculated as the time between recruitment and the date of the occurrence to cataract surgery, the time to the last visit of the follow-up, date of death, or the end of the study. Hazard ratios and 95% CIs for cataract incidence were estimated with a multivariable Cox proportional hazards model. Participants were community-dwelling men (44.2%; n = 868) and women (55.8%; n = 1086), and the mean (SD) age was 66.3 (6.1) years. After a median of 5.6 years follow-up, we documented a total of 768 new cataracts. Participants in the highest tertile of dietary vitamin K1 intake had a lower risk of cataracts than those in the lowest tertile (hazard ratio, 0.71; 95% CI, 0.58-0.88; P = .002), after adjusting for potential confounders. High intake of dietary vitamin K1 was associated with a reduced risk of cataracts in an elderly Mediterranean population even after adjusting by other potential confounders. isrctn.org: ISRCTN35739639.

  13. Complex Association between Alanine Aminotransferase Activity and Mortality in General Population: A Systematic Review and Meta-Analysis of Prospective Studies

    PubMed Central

    Que, Shuping; Wang, Linlin; Qin, Xue

    2014-01-01

    Objective Controversy exists in using alanine aminotransferase (ALT) activity for predicting long-term survival. Therefore, this research study investigated the association between ALT activity and mortality through a systematic review and meta-analysis of previous prospective studies. Methods Electronic literature databases, including PubMed, Embase, and the Institute for Scientific Information (ISI), were searched for relevant prospective observational studies (published before Dec 30, 2013) on the association between baseline ALT activity and ensuing all-cause/disease-specific mortality. Information on nationality, sample size, participant characteristics, follow-up duration, comparison, outcome assessment, hazard ratios (HRs) and adjusted covariates was extracted. Pooled HRs and corresponding 95% confidence intervals (CIs) were separately calculated for categorical risk estimates (highest vs. lowest ALT categories) and continuous risk estimates (per 5 U/l of ALT increment) in subgroups separated by age (<70/≥70 years). Results A total of twelve prospective cohort studies, totaling 206,678 participants and 16,249 deaths, were identified and analyzed. In the younger age group, the pooled HR for mortality related to liver-disease was about 1.24 (95% CI: 1.23–1.25) per 5 U/l of ALT increment. The dose-response HRs of all-cause mortality, cardiovascular (CV) disease-related mortality, and cancer-related mortality were 0.91 (0.88–0.94), 0.91 (0.85–0.96), 0.92 (0.86–0.98) respectively per 5 U/l of ALT elevation, with insignificant heterogeneity in the older population. There was an approximate decrease of 4‰ observed on HRs of all-cause, CV-related, and cancer-related mortality followed with one year's increment through meta-regression (all P<0.05). Conclusions The ALT-mortality association was inconsistent and seems particularly susceptible to age after synthesizing the previous prospective studies. In terms of the age, ALT activity was more valuable in

  14. Complex association between alanine aminotransferase activity and mortality in general population: a systematic review and meta-analysis of prospective studies.

    PubMed

    Liu, Zhengtao; Ning, Huaijun; Que, Shuping; Wang, Linlin; Qin, Xue; Peng, Tao

    2014-01-01

    Controversy exists in using alanine aminotransferase (ALT) activity for predicting long-term survival. Therefore, this research study investigated the association between ALT activity and mortality through a systematic review and meta-analysis of previous prospective studies. Electronic literature databases, including PubMed, Embase, and the Institute for Scientific Information (ISI), were searched for relevant prospective observational studies (published before Dec 30, 2013) on the association between baseline ALT activity and ensuing all-cause/disease-specific mortality. Information on nationality, sample size, participant characteristics, follow-up duration, comparison, outcome assessment, hazard ratios (HRs) and adjusted covariates was extracted. Pooled HRs and corresponding 95% confidence intervals (CIs) were separately calculated for categorical risk estimates (highest vs. lowest ALT categories) and continuous risk estimates (per 5 U/l of ALT increment) in subgroups separated by age (<70/≥ 70 years). A total of twelve prospective cohort studies, totaling 206,678 participants and 16,249 deaths, were identified and analyzed. In the younger age group, the pooled HR for mortality related to liver-disease was about 1.24 (95% CI: 1.23-1.25) per 5 U/l of ALT increment. The dose-response HRs of all-cause mortality, cardiovascular (CV) disease-related mortality, and cancer-related mortality were 0.91 (0.88-0.94), 0.91 (0.85-0.96), 0.92 (0.86-0.98) respectively per 5 U/l of ALT elevation, with insignificant heterogeneity in the older population. There was an approximate decrease of 4‰ observed on HRs of all-cause, CV-related, and cancer-related mortality followed with one year's increment through meta-regression (all P<0.05). The ALT-mortality association was inconsistent and seems particularly susceptible to age after synthesizing the previous prospective studies. In terms of the age, ALT activity was more valuable in predicting mortality in the older population

  15. Association of serum ferritin levels with smoking and lung function in the Korean adult population: analysis of the fourth and fifth Korean National Health and Nutrition Examination Survey

    PubMed Central

    Lee, Chan Ho; Goag, Eun Kyung; Lee, Su Hwan; Chung, Kyung Soo; Jung, Ji Ye; Park, Moo Suk; Kim, Young Sam; Kim, Se Kyu; Chang, Joon; Song, Joo Han

    2016-01-01

    Background Iron-catalyzed oxidative stress contributes to lung injury after exposure to various toxins, including cigarette smoke. An oxidant/antioxidant imbalance is considered to play a critical role in the pathogenesis of COPD. Ferritin is a key protein in iron homeostasis, and its capacity to oxidize and sequester the metal preventing iron prooxidant activity implicates its possible role in the alteration of antioxidant imbalance. We investigated the relationship among cigarette smoking, lung function, and serum ferritin concentration in a large cohort representative of the Korean adult population. Materials and methods Among 50,405 participants of the Korean National Health and Nutrition Examination Survey from 2010 to 2014, 15,239 adult subjects older than 40 years with serum ferritin levels and spirometric data were selected for this study. Results The mean age was 56.5 years for men (43%) and 56.9 years for women (57%). The prevalence of airway obstruction was 13.4%, which was significantly higher in men than in women, and increased in former or current smokers. The median levels of serum ferritin were highest in the airway obstruction group, followed by the restrictive pattern group, and lowest in the normal lung function group. The median ferritin levels were increased by smoking status and amounts in each spirometric subgroup. In multivariable regression analysis, serum ferritin was positively associated with forced expiratory volume in 1 second and forced expiratory volume in 1 second/forced vital capacity, whereas the smoking amount was negatively associated with the adjustment with age, sex, height, and weight. Conclusion Serum ferritin levels were increased in former or current smokers and were increased with smoking amount in all subgroups of participants categorized according to spirometric results. The result was also evident in the subgroups divided by obstructive severity. While smoking amount was inversely related to lung function, higher

  16. Projection of Diabetes Population Size and Associated Economic Burden through 2030 in Iran: Evidence from Micro-Simulation Markov Model and Bayesian Meta-Analysis

    PubMed Central

    Javanbakht, Mehdi; Mashayekhi, Atefeh; Baradaran, Hamid R.; Haghdoost, AliAkbar; Afshin, Ashkan

    2015-01-01

    Background The aim of this study was to estimate the economic burden of diabetes mellitus (DM) in Iran from 2009 to 2030. Methods A Markov micro-simulation (MM) model was developed to predict the DM population size and associated economic burden. Age- and sex-specific prevalence and incidence of diagnosed and undiagnosed DM were derived from national health surveys. A systematic review was performed to identify the cost of diabetes in Iran and the mean annual direct and indirect costs of patients with DM were estimated using a random-effect Bayesian meta-analysis. Face, internal, cross and predictive validity of the MM model were assessed by consulting an expert group, performing sensitivity analysis (SA) and comparing model results with published literature and national survey reports. Sensitivity analysis was also performed to explore the effect of uncertainty in the model. Results We estimated 3.78 million cases of DM (2.74 million diagnosed and 1.04 million undiagnosed) in Iran in 2009. This number is expected to rise to 9.24 million cases (6.73 million diagnosed and 2.50 million undiagnosed) by 2030. The mean annual direct and indirect costs of patients with DM in 2009 were US$ 556 (posterior standard deviation, 221) and US$ 689 (619), respectively. Total estimated annual cost of DM was $3.64 (2009 US$) billion (including US$1.71 billion direct and US$1.93 billion indirect costs) in 2009 and is predicted to increase to $9.0 (in 2009 US$) billion (including US$4.2 billion direct and US$4.8 billion indirect costs) by 2030. Conclusions The economic burden of DM in Iran is predicted to increase markedly in the coming decades. Identification and implementation of effective strategies to prevent and manage DM should be considered as a public health priority. PMID:26200913

  17. Projection of Diabetes Population Size and Associated Economic Burden through 2030 in Iran: Evidence from Micro-Simulation Markov Model and Bayesian Meta-Analysis.

    PubMed

    Javanbakht, Mehdi; Mashayekhi, Atefeh; Baradaran, Hamid R; Haghdoost, AliAkbar; Afshin, Ashkan

    2015-01-01

    The aim of this study was to estimate the economic burden of diabetes mellitus (DM) in Iran from 2009 to 2030. A Markov micro-simulation (MM) model was developed to predict the DM population size and associated economic burden. Age- and sex-specific prevalence and incidence of diagnosed and undiagnosed DM were derived from national health surveys. A systematic review was performed to identify the cost of diabetes in Iran and the mean annual direct and indirect costs of patients with DM were estimated using a random-effect Bayesian meta-analysis. Face, internal, cross and predictive validity of the MM model were assessed by consulting an expert group, performing sensitivity analysis (SA) and comparing model results with published literature and national survey reports. Sensitivity analysis was also performed to explore the effect of uncertainty in the model. We estimated 3.78 million cases of DM (2.74 million diagnosed and 1.04 million undiagnosed) in Iran in 2009. This number is expected to rise to 9.24 million cases (6.73 million diagnosed and 2.50 million undiagnosed) by 2030. The mean annual direct and indirect costs of patients with DM in 2009 were US$ 556 (posterior standard deviation, 221) and US$ 689 (619), respectively. Total estimated annual cost of DM was $3.64 (2009 US$) billion (including US$1.71 billion direct and US$1.93 billion indirect costs) in 2009 and is predicted to increase to $9.0 (in 2009 US$) billion (including US$4.2 billion direct and US$4.8 billion indirect costs) by 2030. The economic burden of DM in Iran is predicted to increase markedly in the coming decades. Identification and implementation of effective strategies to prevent and manage DM should be considered as a public health priority.

  18. Analysis of Polymorphisms in Genes (AGT, MTHFR, GPIIIa, and GSTP1) Associated with Hypertension, Thrombophilia and Oxidative Stress in Mestizo and Amerindian Populations of México

    PubMed Central

    Juárez-Velázquez, Rocio; Canto, Patricia; Canto-Cetina, Thelma; Rangel-Villalobos, Hector; Rosas-Vargas, Haydee; Rodríguez, Maricela; Canizales-Quinteros, Samuel; Velázquez Wong, Ana Claudia; Ordoñez-Razo, Rosa María; Vilchis-Dorantes, Guadalupe; Coral-Vázquez, Ramón Mauricio

    2010-01-01

    Several polymorphisms related to hypertension, thrombophilia, and oxidative stress has been associated with the development of cardiovascular disease. We analyzed the frequency of M235T angiotensinogen (AGT), A222V 5,10 methylenete-trahydrofolate reductase (MTHFR), L33P glycoprotein IIIa (GPIIIa), and I105V glutathione S-transferase P1 (GSTP1) polymorphisms in 285 individuals belonging to Mexican-Mestizo and five Amerindian population from México, by real time PCR allelic discrimination. Allele and genotype frequencies were compared using χ2 tests. All populations followed the Hardy Weinberg equilibrium for assay markers with the exception of the Triki, whose were in Hardy Weinberg dysequilibrium for the glutathione S-transferase P1 polymorphism. Interestingly, according to all the analyzed single nucleotide polymorphisms (SNPs), the Triki population was the most differentiated and homogeneous group of the six populations analyzed. A comparison of our data with those previously published for some Caucasian, Asian and Black populations showed quite significant differences. These differences were remarkable with all the Mexican populations having a lower frequency of the 105V allele of the glutathione S-transferase P1 and reduced occurrence of the 222A allele of the 5,10 methylenetetrahydrofolate reductase. Our results show the genetic diversity among different Mexican populations and with other racial groups. PMID:20592457

  19. Analysis of polymorphisms in genes (AGT, MTHFR, GPIIIa, and GSTP1) associated with hypertension, thrombophilia and oxidative stress in Mestizo and Amerindian populations of México.

    PubMed

    Juárez-Velázquez, Rocio; Canto, Patricia; Canto-Cetina, Thelma; Rangel-Villalobos, Hector; Rosas-Vargas, Haydee; Rodríguez, Maricela; Canizales-Quinteros, Samuel; Velázquez Wong, Ana Claudia; Ordoñez-Razo, Rosa María; Vilchis-Dorantes, Guadalupe; Coral-Vázquez, Ramón Mauricio

    2010-01-01

    Several polymorphisms related to hypertension, thrombophilia, and oxidative stress has been associated with the development of cardiovascular disease. We analyzed the frequency of M235T angiotensinogen (AGT), A222V 5,10 methylenete-trahydrofolate reductase (MTHFR), L33P glycoprotein IIIa (GPIIIa), and I105V glutathione S-transferase P1 (GSTP1)} polymorphisms in 285 individuals belonging to Mexican-Mestizo and five Amerindian population from México, by real time PCR allelic discrimination. Allele and genotype frequencies were compared using chi square tests. All populations followed the Hardy Weinberg equilibrium for assay markers with the exception of the Triki, whose were in Hardy Weinberg dysequilibrium for the glutathione S-transferase P1 polymorphism. Interestingly, according to all the analyzed single nucleotide polymorphisms (SNPs), the Triki population was the most differentiated and homogeneous group of the six populations analyzed. A comparison of our data with those previously published for some Caucasian, Asian and Black populations showed quite significant differences. These differences were remarkable with all the Mexican populations having a lower frequency of the 105V allele of the glutathione S-transferase P1 and reduced occurrence of the 222A allele of the 5,10 methylenetetrahydrofolate reductase. Our results show the genetic diversity among different Mexican populations and with other racial groups.

  20. A Comparative Analysis of the Validity of US State- and County-Level Social Capital Measures and Their Associations with Population Health

    ERIC Educational Resources Information Center

    Lee, Chul-Joo; Kim, Daniel

    2013-01-01

    The goals of this study were to validate a number of available collective social capital measures at the US state and county levels, and to examine the relative extent to which these social capital measures are associated with population health outcomes. Measures of social capital at the US state level included aggregate indices based on the…

  1. A Comparative Analysis of the Validity of US State- and County-Level Social Capital Measures and Their Associations with Population Health

    ERIC Educational Resources Information Center

    Lee, Chul-Joo; Kim, Daniel

    2013-01-01

    The goals of this study were to validate a number of available collective social capital measures at the US state and county levels, and to examine the relative extent to which these social capital measures are associated with population health outcomes. Measures of social capital at the US state level included aggregate indices based on the…

  2. Association between mRNA expression of chemotherapy-related genes and clinicopathological features in colorectal cancer: A large-scale population analysis.

    PubMed

    Shimamoto, Yuji; Nukatsuka, Mamoru; Takechi, Teiji; Fukushima, Masakazu

    2016-02-01

    To establish the individualized treatment of patients with colorectal cancer, factors associated with chemotherapeutic effects should be identified. However, to the best of our knowledge, few studies are available on this topic, although it is known that the prognosis of patients and sensitivity to chemotherapy depend on the location of the tumor and that the tumor location is important for individualized treatment. In this study, primary tumors obtained from 1,129 patients with colorectal cancer were used to measure the mRNA expression levels of the following genes associated with the effects of standard chemotherapy for colorectal cancer: 5-fluorouracil (5-FU)-related thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD) and thymidine phosphorylase (TYMP); folate-related dihydrofolate reductase (DHFR), folylpolyglutamate synthase (FPGS) and gamma-glutamyl hydrolase (GGH); irinotecan-related topoisomerase I (TOP1); oxaliplatin-related excision repair cross-complementing 1 (ERCC1); biologic agent-related vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). Large-scale population analysis was performed to determine the association of gene expression with the clinicopathological features, in particular, the location of the colorectal cancer. From the results of our analysis of the mRNA expression of these 10 genes, we noted the strongest correlation between DPYD and TYMP, followed by TYMS and DHFR. The location of the colorectal cancer was classified into 4 regions (the right‑ and left-sided colon, rectosigmoid and rectum) and was compared with gene expression. A significant difference in all genes, apart from VEGF, was noted. Of the remaining 9 genes, the highest expression of TYMS and DPYD was observed in the right‑sided colon; the highest expression of GGH and EGFR was noted in the left-sided colon; the highest expression of DHFR, FPGS, TOP1 and ERCC1 was noted in the rectosigmoid, whereas TYMP expression was

  3. Association between mRNA expression of chemotherapy-related genes and clinicopathological features in colorectal cancer: A large-scale population analysis

    PubMed Central

    SHIMAMOTO, YUJI; NUKATSUKA, MAMORU; TAKECHI, TEIJI; FUKUSHIMA, MASAKAZU

    2016-01-01

    To establish the individualized treatment of patients with colorectal cancer, factors associated with chemotherapeutic effects should be identified. However, to the best of our knowledge, few studies are available on this topic, although it is known that the prognosis of patients and sensitivity to chemotherapy depend on the location of the tumor and that the tumor location is important for individualized treatment. In this study, primary tumors obtained from 1,129 patients with colorectal cancer were used to measure the mRNA expression levels of the following genes associated with the effects of standard chemotherapy for colorectal cancer: 5-fluorouracil (5-FU)-related thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD) and thymidine phosphorylase (TYMP); folate-related dihydrofolate reductase (DHFR), folylpolyglutamate synthase (FPGS) and gamma-glutamyl hydrolase (GGH); irinotecan-related topoisomerase I (TOP1); oxaliplatin-related excision repair cross-complementing 1 (ERCC1); biologic agent-related vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). Large-scale population analysis was performed to determine the association of gene expression with the clinicopathological features, in particular, the location of the colorectal cancer. From the results of our analysis of the mRNA expression of these 10 genes, we noted the strongest correlation between DPYD and TYMP, followed by TYMS and DHFR. The location of the colorectal cancer was classified into 4 regions (the right- and left-sided colon, rectosigmoid and rectum) and was compared with gene expression. A significant difference in all genes, apart from VEGF, was noted. Of the remaining 9 genes, the highest expression of TYMS and DPYD was observed in the right-sided colon; the highest expression of GGH and EGFR was noted in the left-sided colon; the highest expression of DHFR, FPGS, TOP1 and ERCC1 was noted in the rectosigmoid, whereas TYMP expression was

  4. Psychotropic Medication Burden and Factors Associated with Antipsychotic Use: An Analysis of a Population-Based Sample of Community-Dwelling Older Persons with Dementia

    PubMed Central

    Rhee, YongJoo; Csernansky, John G.; Emanuel, Linda L.; Chang, Chang-Gok; Shega, Joseph W.

    2011-01-01

    Objectives To estimate the proportion of community dwelling older adults with dementia being prescribed a psychotropic and identify patient and caregiver factors associated with antipsychotics use. Methods Retrospective cohort study of The Aging, Demographics, and Memory Study (ADAMS) from 2002 to 2004 designed to assess dementia severity and service use among community-dwelling older adults. The frequency of psychotropic medication (antipsychotics, antidepressants, anticonvulsants and benzodiazepines) use was tabulated and weighted to the US population by dementia diagnosis. Logistic regression analysis identified factors associated with antipsychotic use. Results The 307 participants of ADAMS had the following dementia diagnosis: Alzheimer’s disease (69.29%), vascular dementia (17.74%) and other dementia (12.39%). The proportion of participants prescribed a psychotropic medication broken down by therapeutic class was as 19.07% antipsychotics, 29.08% antidepressants, 9.84% benzodiazepines, and 8.85% anticonvulsants. Older adults with dementia were significantly more likely to receive an antipsychotic if they had moderate dementia (OR =7.4, p<0.05), or severe dementia (OR=5.80, p<0.05), compared to mild dementia or were diagnosed with Alzheimer (OR =6.7, p<0.05) dementia compared to vascular dementia. Older adults with dementia who lived with their caregivers in were significantly less likely to be medicated with antipsychotics (OR= 0.19, p<0.05) compared to those who lived alone. Also, persons with dementia were significantly less likely to be prescribed an antipsychotic if the caregivers were clinically depressed (OR=0.03, p<0.05) compared to those who were not depressed. Conclusion We found psychotropic medication use is common among community-dwelling older adults with dementia. Caregivers appear to have a substantial impact on whether or not an antipsychotic is prescribed, which adds additional complexity to conversations discussing the risk-benefit ratio of

  5. Pediatric specialist care is associated with a lower risk of bowel resection in children with intussusception: a population-based analysis.

    PubMed

    McAteer, Jarod P; Kwon, Steve; LaRiviere, Cabrini A; Oldham, Keith T; Goldin, Adam B

    2013-08-01

    Although previous studies have shown that radiologic intussusception reduction is more likely at children's hospitals, no study to date has compared outcomes among children advancing to surgical intervention. We hypothesized that rates of bowel resection would differ between hospitals with and without pediatric surgeons. We conducted a population-based retrospective cohort study using Washington State discharge records. All children younger than 18 years undergoing operative intussusception reduction between 1999 and 2009 were included (n = 327). Data were collected on demographics, disease severity, comorbidities, and concomitant gastrointestinal pathology. Multivariate logistic regression was used to estimate odds of intestinal resection during operative intussusception reduction. Pediatric hospitals treated a smaller proportion of children older than 4 years of age (12.1% vs 44.4%), as well as a greater proportion of Medicaid patients (50.9% vs 42.6%). Patients at pediatric hospitals had a lower prevalence of underlying intestinal anomalies or identifiable mass lesions (14.3% vs 16.7%). "Severe disease" (perforation, ischemia, acidosis) was more common at pediatric hospitals (17.6% vs 9.3%). Overall, bowel resection was more commonly performed at nonpediatric hospitals (59.3% vs 33.0%). On multivariate analysis, the odds of bowel resection were significantly lower at pediatric compared with nonpediatric hospitals (odds ratio [OR] 0.20, p < 0.001), and this association was strongest in younger patients. Adjusted odds of postoperative complications were greater for bowel resection patients (OR 2.83, p < 0.001). Bowel resection during operative intussusception reduction is more likely at hospitals without pediatric surgeons, and is associated with increased complications. Improved outcomes may be achieved by efforts aimed at standardizing care and decreasing variability in the treatment of pediatric intussusception. Copyright © 2013 American College of Surgeons

  6. Association between hepatitis B virus/hepatitis C virus infection and primary hepatocellular carcinoma risk: A meta-analysis based on Chinese population.

    PubMed

    Li, Libo; Lan, Xiaolin

    2016-12-01

    To assess the relationship between hepatitis B virus (HBV), hepatitis C virus (HCV), and HBV/HCV double infection and hepatocellular carcinoma risk in Chinese population. The databases of PubMed and CNKI were electronic searched by reviewers according to the searching words of HBV, HCV, and hepatocellular carcinoma. The related case-control studies or cohort studies were included. The association between virus infection and hepatocellular carcinoma risk was demonstrated by odds ratio (OR) and 95% confidence interval (95% CI). The data were pooled by fixed or random effects model according to the statistical heterogeneity. The publication bias was assessed by Begg's funnel plot and Egger's linear regression test. Finally, 13 publications were included in this meta-analysis. For significant statistical heterogeneity (I2 = 99.8%,P = 0.00), the OR was pooled by random effects model. The pooled results showed that HBV infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 58.01, 95% CI: 44.27-71.75); statistical heterogeneity analysis showed that significant heterogeneity existed in evaluation of HCV infection and hepatocellular carcinoma risk across the included 13 studies I2 = 77.78%, P = 0.00). The OR was pooled by random effects model. The pooled results showed that HCV infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 2.34, 95% CI: 1.20-3.47); significant heterogeneity did not exist in evaluation HBV/HCV double infection and hepatocellular carcinoma risk for the included 13 studies (I2 = 0.00%,P = 0.80). The OR was pooled by fixed effects model. The pooled results showed that HBV/HCV double infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 11.39, 95% CI: 4.58-18.20). No publication bias was found in the aspects of HBV, HCV, and HBV/HCV double infection and hepatocellular carcinoma. For Chinese population, HBV, HCV or HBV/HCV double infection can

  7. Associations of Polymorphisms in MTHFR Gene with the Risk of Age-Related Cataract in Chinese Han Population: A Genotype-Phenotype Analysis

    PubMed Central

    Wei, Li; Han, Ya-di; Cui, Ning-hua; Huang, Zhu-liang; Li, Zu-hua; Zheng, Fang; Yan, Ming

    2015-01-01

    Homocysteine (Hcy) is a potential risk factor for age-related cataract (ARC). Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme for Hcy metabolism, and variants of MTHFR may affect MTHFR enzyme activity. This study mainly evaluated the associations between variants in MTHFR gene, plasma MTHFR enzyme activity, total Hcy (tHcy) levels and ARC risk in Chinese population. Four single nucleotide polymorphisms (SNPs) in MTHFR gene were genotyped using the high-resolution melting (HRM) method in 502 ARC patients (mean age, 70.2 [SD, 9.0], 46.0% male) and 890 healthy controls (mean age, 67.1 [SD, 11.1], 47.6% male). The plasma MTHFR activity, folic acid (FA), vitamins B12 and B6 levels were detected by enzyme-linked immunosorbent assays (ELISA). The plasma tHcy levels were measured by an automated enzymatic assay. After the Bonferroni correction, the minor allele T of SNP rs1801133 showed a significant association with an increased risk of overall ARC (OR = 1.26, P = 0.003). Consistent association was also found between SNP rs1801133 and cortical ARC risk (OR = 1.44, P = 0.003). Haplotype analyses revealed an adverse effect of the haplotype "C-A-T-C" (alleles in order of SNPs rs3737967, rs1801131, rs1801133 and rs9651118) on ARC risk (OR = 1.55, P = 0.003). Moreover, in a joint analysis of SNPs rs9651118 and rs1801133, subjects with two unfavorable genotypes had a 1.76-fold increased risk of ARC compared with the reference group, and a statistically significant dose-response trend (Ptrend = 0.001) was also observed. Further, in healthy controls and patients with cortical ARC, the allele T of SNP rs1801133 and the increasing number of unfavorable genotypes were significantly correlated with decreased MTHFR activity as well as increased tHcy levels. However, there was no significant association between FA, vitamins B12, B6 levels and MTHFR variants. Our data indicated that variants in MTHFR gene might individually and jointly influence susceptibility to ARC by

  8. Population pharmacokinetic analysis of bisoprolol.

    PubMed

    Grevel, J; Thomas, P; Whiting, B

    1989-07-01

    The technique of population pharmacokinetic analysis was employed to study the variability in the dose concentration relationship of bisoprolol during its clinical development. The influence of demographic factors on the variability of clearance was investigated in 3 different populations: group I, patients (including an elderly group) with essential hypertension receiving multiple oral doses of bisoprolol 10 or 20mg for 3 months; group II, patients with different degrees of renal impairment and healthy controls; and group III, patients with different types of hepatic impairment and healthy controls. Patients and controls in groups II and III received only a single oral dose of bisoprolol 10mg. The 3 data sets were analysed separately, using a non-linear mixed effects model (the NONMEM program). A 2-compartment pharmacokinetic model with first-order absorption described the data adequately. The typical values of volume of central compartment, volume of distribution at steady-state and the absorption rate constant for the 3 populations were: for group I, 68L, 235L, and 0.7h-1; for group II, 28L, 179L, and 0.3h-1; and for group III, 55L, 256L, and 0.4h-1, respectively. Plasma clearance was related to age in group I, to serum creatinine in group II and to aspartate transaminase activity in group III. The 68% confidence limits for clearance and elimination half-life were 8.2 to 21.5 L/h and 7.6 to 19.7h, respectively, for 50-year-old patients in group I. The analysis predicted that progressive increases in serum creatinine or aspartate transaminase activity will result in only a 50% reduction of clearance.

  9. Association between MTHFR C677T polymorphism and diabetic nephropathy in the Chinese population: An updated meta-analysis and review.

    PubMed

    Xiong, Xuan; Lin, Xiao-Kun; Xiao, Xiao; Qin, Dan-Ping; Zhou, Dao-Yuan; Hu, Jian-Guang; Liu, Yan; Zhong, Xiao-Shi

    2016-01-01

    To clarify the effects of MTHFR C677T polymorphism on the risk of diabetic nephropathy (DN) in the Chinese population, an updated meta-analysis was performed. Related studies were identified from PubMed, Springer Link, Ovid and Chinese Databases up to 24 February 2015. A total of 15 studies including 1227 DN cases, 586 healthy controls and 1277 diabetes mellitus (DM) controls were involved in this meta-analysis. Overall, a significantly elevated risk of DN was associated with all variants of MTHFR C677T when compared with the healthy group (T vs C, odds ratio (OR) = 2.22, 95% confidence interval (CI) = 1.88-2.61; TT vs CC, OR = 4.22, 95% CI = 3.02-5.90; TT + CT vs CC, OR = 2.62, 95% CI = 2.07-3.31; TT vs CC + CT, OR = 2.81, 95% CI = 2.08-3.81) or DM (T vs C, OR = 1.78, 95% CI = 1.59-2.00; TT vs CC, OR = 2.95, 95% CI = 2.33-3.73; TT + CT vs CC, OR = 1.93, 95% CI = 1.63-2.29; TT vs CC + CT, OR = 2.31, 95% CI = 1.87-2.84). In subgroup analyses stratified by ethnicity and geographic areas, it revealed the significant results in Chinese Han, in North and South China. The risk conferred by MTHFR C677T polymorphism is higher in North China than in South China. This meta-analysis showed that the MTHFR C677T variants may influence DN risk in Chinese, and further studies with gene-gene and gene-environment interactions are required for definite conclusions.

  10. Analysis of recently identified prostate cancer susceptibility loci in a population-based study: associations with family history and clinical features.

    PubMed

    Fitzgerald, Liesel M; Kwon, Erika M; Koopmeiners, Joseph S; Salinas, Claudia A; Stanford, Janet L; Ostrander, Elaine A

    2009-05-01

    Two recent genome-wide association studies have highlighted several single nucleotide polymorphisms (SNPs) purported to be associated with prostate cancer risk. We investigated the significance of these SNPs in a population-based study of Caucasian men, testing the effects of each SNP in relation to family history of prostate cancer and the clinicopathologic features of the disease. We genotyped 13 SNPs in 1,308 prostate cancer patients and 1,267 unaffected controls frequency matched to cases by five-year age groups. The association of each SNP with disease risk stratified by family history of prostate cancer and clinicopathologic features of the disease was calculated with the use of logistic and polytomous regression. These results confirm the importance of multiple, previously reported SNPs in relation to prostate cancer susceptibility; 11 of the 13 SNPs were significantly associated with risk of developing prostate cancer. However, none of the SNP associations were of comparable magnitude with that associated with having a first-degree family history of the disease. Risk estimates associated with SNPs rs4242382 and rs2735839 varied by family history, whereas risk estimates for rs10993994 and rs5945619 varied by Gleason score. Our results confirm that several recently identified SNPs are associated with prostate cancer risk; however, the variant alleles only confer a low to moderate relative risk of disease and are generally not associated with more aggressive disease features.

  11. A Comparative Analysis of the Validity of US State- and County-Level Social Capital Measures and Their Associations with Population Health

    PubMed Central

    Lee, Chul-joo; Kim, Daniel

    2014-01-01

    The goals of this study were to validate a number of available collective social capital measures at the U.S. state and county levels, and to examine the relative extent to which these social capital measures are associated with population health outcomes. Measures of social capital at the U.S. state level included aggregate indices based on the Annenberg National Health Communication Survey (ANHCS) and the Behavioral Risk Factor Surveillance System (BRFSS), Petris Social Capital Index (PSCI), Putnam’s index, and Kim et al.’s scales. County-level measures consisted of Rupasingha et al.’s social capital index (RGFI) and a BRFSS-derived measure. These measures, except for the PSCI, showed evidence of acceptable validity. Moreover, we observed differences across the social capital measures in their associations with population health outcomes. The implications of the findings for future research in this area are discussed. PMID:25574069

  12. A Comparative Analysis of the Validity of US State- and County-Level Social Capital Measures and Their Associations with Population Health.

    PubMed

    Lee, Chul-Joo; Kim, Daniel

    2013-03-01

    The goals of this study were to validate a number of available collective social capital measures at the U.S. state and county levels, and to examine the relative extent to which these social capital measures are associated with population health outcomes. Measures of social capital at the U.S. state level included aggregate indices based on the Annenberg National Health Communication Survey (ANHCS) and the Behavioral Risk Factor Surveillance System (BRFSS), Petris Social Capital Index (PSCI), Putnam's index, and Kim et al.'s scales. County-level measures consisted of Rupasingha et al.'s social capital index (RGFI) and a BRFSS-derived measure. These measures, except for the PSCI, showed evidence of acceptable validity. Moreover, we observed differences across the social capital measures in their associations with population health outcomes. The implications of the findings for future research in this area are discussed.

  13. Bacterial Populations Associated with Smokeless Tobacco Products

    PubMed Central

    Han, Jing; Sanad, Yasser M.; Deck, Joanna; Sutherland, John B.; Li, Zhong; Walters, Matthew J.; Duran, Norma; Holman, Matthew R.

    2016-01-01

    ABSTRACT There are an estimated 8 million users of smokeless tobacco products (STPs) in the United States, and yet limited data on microbial populations within these products exist. To better understand the potential microbiological risks associated with STP use, a study was conducted to provide a baseline microbiological profile of STPs. A total of 90 samples, representing 15 common STPs, were purchased in metropolitan areas in Little Rock, AR, and Washington, DC, in November 2012, March 2013, and July 2013. Bacterial populations were evaluated using culture, pyrosequencing, and denaturing gradient gel electrophoresis (DGGE). Moist-snuff products exhibited higher levels of bacteria (average of 1.05 × 106 CFU/g STP) and diversity of bacterial populations than snus (average of 8.33 × 101 CFU/g STP) and some chewing tobacco products (average of 2.54 × 105 CFU/g STP). The most common species identified by culturing were Bacillus pumilus, B. licheniformis, B. safensis, and B. subtilis, followed by members of the genera Oceanobacillus, Staphylococcus, and Tetragenococcus. Pyrosequencing analyses of the 16S rRNA genes identified the genera Tetragenococcus, Carnobacterium, Lactobacillus, Geobacillus, Bacillus, and Staphylococcus as the predominant taxa. Several species identified are of possible concern due to their potential to cause opportunistic infections and reported abilities to reduce nitrates to nitrites, which may be an important step in the formation of carcinogenic tobacco-specific N′-nitrosamines. This report provides a microbiological baseline to help fill knowledge gaps associated with microbiological risks of STPs and to inform potential regulations regarding manufacture and testing of STPs. IMPORTANCE It is estimated that there 8 million users of smokeless tobacco products (STPs) in the United States; however, there are limited data on microbial populations that exist within these products. The current study was undertaken to better understand the

  14. Bacterial Populations Associated with Smokeless Tobacco Products.

    PubMed

    Han, Jing; Sanad, Yasser M; Deck, Joanna; Sutherland, John B; Li, Zhong; Walters, Matthew J; Duran, Norma; Holman, Matthew R; Foley, Steven L

    2016-10-15

    There are an estimated 8 million users of smokeless tobacco products (STPs) in the United States, and yet limited data on microbial populations within these products exist. To better understand the potential microbiological risks associated with STP use, a study was conducted to provide a baseline microbiological profile of STPs. A total of 90 samples, representing 15 common STPs, were purchased in metropolitan areas in Little Rock, AR, and Washington, DC, in November 2012, March 2013, and July 2013. Bacterial populations were evaluated using culture, pyrosequencing, and denaturing gradient gel electrophoresis (DGGE). Moist-snuff products exhibited higher levels of bacteria (average of 1.05 × 10(6) CFU/g STP) and diversity of bacterial populations than snus (average of 8.33 × 10(1) CFU/g STP) and some chewing tobacco products (average of 2.54 × 10(5) CFU/g STP). The most common species identified by culturing were Bacillus pumilus, B. licheniformis, B. safensis, and B. subtilis, followed by members of the genera Oceanobacillus, Staphylococcus, and Tetragenococcus. Pyrosequencing analyses of the 16S rRNA genes identified the genera Tetragenococcus, Carnobacterium, Lactobacillus, Geobacillus, Bacillus, and Staphylococcus as the predominant taxa. Several species identified are of possible concern due to their potential to cause opportunistic infections and reported abilities to reduce nitrates to nitrites, which may be an important step in the formation of carcinogenic tobacco-specific N'-nitrosamines. This report provides a microbiological baseline to help fill knowledge gaps associated with microbiological risks of STPs and to inform potential regulations regarding manufacture and testing of STPs. It is estimated that there 8 million users of smokeless tobacco products (STPs) in the United States; however, there are limited data on microbial populations that exist within these products. The current study was undertaken to better understand the potential

  15. Mosquito populations dynamics associated with climate variations.

    PubMed

    Wilke, André Barretto Bruno; Medeiros-Sousa, Antônio Ralph; Ceretti-Junior, Walter; Marrelli, Mauro Toledo

    2017-02-01

    Mosquitoes are responsible for the transmission of numerous serious pathogens. Members of the Aedes and Culex genera, which include many important vectors of mosquito-borne diseases, are highly invasive and adapted to man-made environments. They are spread around the world involuntarily by humans and are highly adapted to urbanized environments, where they are exposed to climate-related abundance drivers. We investigated Culicidae fauna in two urban parks in the city of São Paulo to analyze the correlations between climatic variables and the population dynamics of mosquitoes in these urban areas. Mosquitoes were collected monthly over one year, and sampling sufficiency was evaluated after morphological identification of the specimens. The average monthly temperature and accumulated rainfall for the collection month and previous month were used to explain climate-related abundance drivers for the six most abundant species (Aedes aegypti, Aedes albopictus, Aedes fluviatilis, Aedes scapularis, Culex nigripalpus and Culex quinquefasciatus) and then analyzed using generalized linear statistical models and the Akaike Information Criteria corrected for small samples (AICc). The strength of evidence in favor of each model was evaluated using Akaike weights, and the explanatory model power was measured by McFadden's Pseudo-R(2). Associations between climate and mosquito abundance were found in both parks, indicating that predictive models based on climate variables can provide important information on mosquito population dynamics. We also found that this association is species-dependent. Urbanization processes increase the abundance of a few mosquito species that are well adapted to man-made environments and some of which are important vectors of pathogens. Predictive models for abundance based on climate variables may help elucidate the population dynamics of urban mosquitoes and their impact on the risk of disease transmission, allowing better predictive scenarios to be

  16. Association between unemployment, income, education level, population size and air pollution in Czech cities: evidence for environmental inequality? A pilot national scale analysis.

    PubMed

    Branis, Martin; Linhartova, Martina

    2012-09-01

    We analyzed differentials in exposure to SO(2), PM(10) and NO(2) among Czech urban populations categorized according to education level, unemployment rate, population size and average annual salary. Altogether 39 cities were included in the analysis. The principal component analysis revealed two factors explaining 72.8% of the data variability. The first factor explaining 44.7% of the data variability included SO(2), PM(10), low education level and high unemployment, documenting that inhabitants with unfavorable socioeconomic status mainly reside in smaller cities with higher concentration levels of combustion-related air pollutants. The second factor explaining 28.1% of the data variability included NO(2), high salary, high education level and large population, suggesting that large cities with residents with higher socioeconomic status are exposed to higher levels of traffic-related air pollution. We conclude that, after more than a decade of free-market economy, the Czech Republic, a former Soviet satellite with a centrally planned economy, displays signs of a certain kind of environmental inequality, since environmental hazards are unevenly distributed among the Czech urban populations. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Variance associated with subject velocity and trial repetition during force platform gait analysis in a heterogeneous population of clinically normal dogs.

    PubMed

    Hans, Eric C; Zwarthoed, Berdien; Seliski, Joseph; Nemke, Brett; Muir, Peter

    2014-12-01

    Factors that contribute to variance in ground reaction forces (GRF) include dog morphology, velocity, and trial repetition. Narrow velocity ranges are recommended to minimize variance. In a heterogeneous population of clinically normal dogs, it was hypothesized that the dog subject effect would account for the majority of variance in peak vertical force (PVF) and vertical impulse (VI) at a trotting gait, and that narrow velocity ranges would be associated with less variance. Data from 20 normal dogs were obtained. Each dog was trotted across a force platform at its habitual velocity, with controlled acceleration (±0.5 m/s(2)). Variance effects from 12 trotting velocity ranges were examined using repeated-measures analysis-of-covariance. Significance was set at P <0.05. Mean dog bodyweight was 28.4 ± 7.4 kg. Individual dog and velocity significantly affected PVF and VI for thoracic and pelvic limbs (P <0.001). Trial number significantly affected thoracic limb PVF (P <0.001). Limb (left or right) significantly affected thoracic limb VI (P = 0.02). The magnitude of variance effects from largest to smallest was dog, velocity, trial repetition, and limb. Velocity ranges of 1.5-2.0 m/s, 1.8-2.2 m/s, and 1.9-2.2 m/s were associated with low variance and no significant effects on thoracic or pelvic limb PVF and VI. A combination of these ranges, 1.5-2.2 m/s, captured a large percentage of trials per dog (84.2 ± 21.4%) with no significant effects on thoracic or pelvic limb PVF or VI. It was concluded that wider velocity ranges facilitate capture of valid trials with little to no effect on GRF in normal trotting dogs. This concept is important for clinical trial design. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. HLA-B*15:02 association with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in an Indian population: a pooled-data analysis and meta-analysis.

    PubMed

    Khor, Amy Hui-Ping; Lim, Kheng-Seang; Tan, Chong-Tin; Wong, Su-Ming; Ng, Ching-Ching

    2014-11-01

    This study aimed to investigate the prevalence and association of HLA-B*15:02 with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (CBZ-SJS/TEN) in the Indian population in Malaysia, which mostly originated from Southern India. HLA-B alleles in five Indian case patients with CBZ-SJS/TEN and 52 CBZ-tolerant controls, and followed by a pooled sample of seven cases from two centers in Malaysia were analyzed. Positive association for HLA-B*15:02 with CBZ-SJS/TEN was detected in Indians (40% [2/5] vs. 3.8% [2/52], odds ratio [OR] 16.7, p = 0.0349), of which 80% (4/5) of the Indian patients originated from Southern India. A pooled sample of seven cases showed stronger association between HLA-B*15:02 and CBZ-SJS/TEN (57.1% [4/7] vs. 3.8% [2/52], OR 33.3, 95% confidence interval [CI] 4.25-162.21, p = 1.05 × 10(-3)). Subsequent meta-analysis on Indians from Malaysia and India further demonstrated a significant and strong association between HLA-B*15:02 and CBZ-SJS/TEN (OR 38.54; 95% CI 6.83-217.34, p < 1.0 × 10(-4)). Our study is the first on Indians predominantly from Southern India that demonstrated HLA-B*15:02 as a strong risk factor for CBZ-SJS/TEN despite a low population allele frequency. This stressed the importance of testing for HLA-B*15:02, irrespective of the ancestral background, including populations with low allele frequency. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  19. Characterization of the metabolic profile associated with serum 25-hydroxyvitamin D: a cross-sectional analysis in population-based data

    PubMed Central

    Vogt, Susanne; Wahl, Simone; Kettunen, Johannes; Breitner, Susanne; Kastenmüller, Gabi; Gieger, Christian; Suhre, Karsten; Waldenberger, Melanie; Kratzsch, Jürgen; Perola, Markus; Salomaa, Veikko; Blankenberg, Stefan; Zeller, Tanja; Soininen, Pasi; Kangas, Antti J; Peters, Annette; Grallert, Harald; Ala-Korpela, Mika; Thorand, Barbara

    2016-01-01

    Background: Numerous observational studies have observed associations between vitamin D deficiency and cardiometabolic diseases, but these findings might be confounded by obesity. A characterization of the metabolic profile associated with serum 25-hydroxyvitamin D [25(OH)D] levels, in general and stratified by abdominal obesity, may help to untangle the relationship between vitamin D, obesity and cardiometabolic health. Methods: Serum metabolomics measurements were obtained from a nuclear magnetic resonance spectroscopy (NMR)- and a mass spectrometry (MS)-based platform. The discovery was conducted in 1726 participants of the population-based KORA-F4 study, in which the associations of the concentrations of 415 metabolites with 25(OH)D levels were assessed in linear models. The results were replicated in 6759 participants (NMR) and 609 (MS) participants, respectively, of the population-based FINRISK 1997 study. Results: Mean [standard deviation (SD)] 25(OH)D levels were 15.2 (7.5) ng/ml in KORA F4 and 13.8 (5.9) ng/ml in FINRISK 1997; 37 metabolites were associated with 25(OH)D in KORA F4 at P < 0.05/415. Of these, 30 associations were replicated in FINRISK 1997 at P < 0.05/37. Among these were constituents of (very) large very-low-density lipoprotein and small low-density lipoprotein subclasses and related measures like serum triglycerides as well as fatty acids and measures reflecting the degree of fatty acid saturation. The observed associations were independent of waist circumference and generally similar in abdominally obese and non-obese participants. Conclusions: Independently of abdominal obesity, higher 25(OH)D levels were associated with a metabolite profile characterized by lower concentrations of atherogenic lipids and a higher degree of fatty acid polyunsaturation. These results indicate that the relationship between vitamin D deficiency and cardiometabolic diseases is unlikely to merely reflect obesity-related pathomechanisms. PMID:27605587

  20. An analysis of population genetic differentiation and genotype-phenotype association across the hybrid zone of carrion and hooded crows using microsatellites and MC1R.

    PubMed

    Haas, Fredrik; Pointer, Marie A; Saino, Nicola; Brodin, Anders; Mundy, Nicholas I; Hansson, Bengt

    2009-01-01

    The all black carrion crow (Corvus corone corone) and the grey and black hooded crow (Corvus corone cornix) meet in a narrow hybrid zone across Europe. To evaluate the degree of genetic differentiation over the hybrid zone, we genotyped crows from the centre and edges of the zone, and from allopatric populations in northern (Scotland-Denmark-Sweden) and southern Europe (western-central northern Italy), at 18 microsatellites and at a plumage candidate gene, the MC1R gene. Allopatric and edge populations were significantly differentiated on microsatellites, and populations were isolated by distance over the hybrid zone in Italy. Single-locus analyses showed that one locus, CmeH9, differentiated populations on different sides of the zone at the same time as showing only weak separation of populations on the same side of the zone. Within the hybrid zone there was no differentiation of phenotypes at CmeH9 or at the set of microsatellites, no excess of heterozygotes among hybrids and low levels of linkage disequilibrium between markers. We did not detect any association between phenotypes and nucleotide variation at MC1R, and the two most common haplotypes occurred in very similar frequencies in carrion and hooded crows. That we found a similar degree of genetic differentiation between allopatric and edge populations irrespectively of their location in relation to the hybrid zone, no differentiation between phenotypes within the hybrid zone, and neither heterozygote excess nor consistent linkage disequilibrium in the hybrid zone, is striking considering that carrion and hooded crows are phenotypically distinct and sometimes recognised as separate species.

  1. Correlation of population parameters leading to power differences in association studies with population stratification.

    PubMed

    He, Y; Jiang, R; Fu, W; Bergen, A W; Swan, G E; Jin, L

    2008-11-01

    The power of statistical tests to measure effect sizes in the presence of population stratification is an important issue for the design and analysis of population-based association studies. Comparisons of statistical tests have shown that the power of different statistical approaches varies in different genetic scenarios. However, the impact of stratified population parameters on statistical power is not yet understood in a general statistical framework, particularly the impact of correlated population parameters. To investigate such impact in detail, we implemented a genetic model for population-based association studies with stratified samples and evaluated the impact on power with different genetic scenarios. The investigation shows that correlation between disease prevalence and risk allele frequency among subpopulations impacts statistical power. In a model with five subpopulations and moderate population divergence (Fst= 0.01), the correlation accounts for more than 85% of power difference. Our results also show that the estimation of genetic effect for candidate loci is biased by population divergence. Beneficial alleles could be wrongly characterized as risk alleles when prevalence differences and divergences of risk loci are large among subpopulations.

  2. On association analysis of rare variants under population substructure: an approach for the detection of subjects that can cause bias in the analysis--T opt: an outlier detection method.

    PubMed

    Qiao, Dandi; Mattheisen, Manuel; Lange, Christoph

    2013-07-01

    For the analysis of rare-variant data in population-based designs, we propose a method to detect study subjects that may create population substructure in the study sample. Our approach is computationally fast and simple, permitting applications to whole-genome sequencing studies. The method does not require the variants to be in linkage equilibrium and can be applied to all the genetic loci that are available in the study. For both rare and common variants, we assess the performance of our approach by its application to the 1000 Genome Project data, and in simulation studies. The results are compared to the commonly used outlier detection algorithm based on principal component analysis (PCA). The statistical power of both approaches to detect outliers are comparable in most of the scenarios, but the power of PCA to detect outliers is lower than the novel approach in the presence of linkage disequilibrium and for subpopulations that are genetically similar. The data analysis and the simulation studies suggest that the number of false-positive results appears to be different for the two approaches. Our approach maintains the type I error rate while the outlier detection approach based on PCA does not. Taking additionally into account the minimal computational requirements of our approach and the ability to incorporate all the marker information, the proposed method will have important application in sequencing studies and genome-wide association studies.

  3. Long-term association between leisure-time physical activity and changes in happiness: analysis of the Prospective National Population Health Survey.

    PubMed

    Wang, Feng; Orpana, Heather M; Morrison, Howard; de Groh, Margaret; Dai, Sulan; Luo, Wei

    2012-12-15

    Happiness is among the most fundamental of all human goals. Although the short-term association between physical activity and happiness is well known, the long-term associations are not. Data from the National Population Health Survey cycles conducted between 1994/1995 and 2008/2009 (cycles 1 through 8) were analyzed. Happy respondents were classified as physically active or inactive at baseline and then were followed up in subsequent cycles to examine their likelihood of becoming unhappy. Individuals who changed their activity level also were examined. After controlling for potential confounding factors, the authors found that leisure-time physical activity (LTPA) was associated with reduced odds of unhappiness after 2 years and 4 years. People who were inactive in 2 consecutive cycles were more than twice as likely to be unhappy as those who remained active in both cycles after 2 years. Compared with those who became active, inactive participants who remained inactive were also more likely to become unhappy. A change in LTPA from active to inactive was associated with increased odds of becoming unhappy 2 years later. This study suggests that LTPA has a long-term association with happiness. Changes in LTPA are associated with subsequent mood status.

  4. Bone fracture risk is not associated with the use of glucagon-like peptide-1 receptor agonists: a population-based cohort analysis.

    PubMed

    Driessen, Johanna H M; Henry, Ronald M A; van Onzenoort, Hein A W; Lalmohamed, Arief; Burden, Andrea M; Prieto-Alhambra, Daniel; Neef, Cees; Leufkens, Hubert G M; de Vries, Frank

    2015-08-01

    Glucagon-like Peptide-1 receptor agonists (GLP1-ra) are a relatively new class of anti-hyperglycemic drugs which may positively affect bone metabolism and thereby decrease (osteoporotic) bone fracture risk. Data on the effect of GLP1-ra on fracture risk are scarce and limited to clinical trial data only. The aim of this study was to investigate, in a population-based cohort, the association between the use of GLP1-ra and bone fracture risk. We conducted a population-based cohort study, with the use of data from the Clinical Practice Research Datalink (CPRD) database (2007-2012). The study population (N = 216,816) consisted of all individuals with type 2 diabetes patients with at least one prescription for a non-insulin anti-diabetic drug and were over 18 years of age. Cox proportional hazards models were used to estimate the hazard ratio of fracture in GLP1-ra users versus never-GLP1-ra users. Time-dependent adjustments were made for age, sex, lifestyle, comorbidity and the use of other drugs. There was no decreased risk of fracture with current use of GLP1-ra compared to never-GLP1-ra use (adjusted HR 0.99, 95 % CI 0.82-1.19). Osteoporotic fracture risk was also not decreased by current GLP1-ra use (adjusted HR 0.97; 95 % CI 0.72-1.32). In addition, stratification according to cumulative dose did not show a decreased bone fracture risk with increasing cumulative GLP1-ra dose. We showed in a population-based cohort study that GLP1-ra use is not associated with a decreased bone fracture risk compared to users of other anti-hyperglycemic drugs. Future research is needed to elucidate the potential working mechanisms of GLP1-ra on bone.

  5. 16S rDNA-based metagenomic analysis of bacterial diversity associated with two populations of the kleptoplastic sea slug Elysia chlorotica and its algal prey Vaucheria litorea.

    PubMed

    Devine, Susan P; Pelletreau, Karen N; Rumpho, Mary E

    2012-08-01

    The molluscan sea slug Elysia chlorotica is best known for its obligate endosymbiosis with chloroplasts (= kleptoplasty) from its algal prey Vaucheria litorea and its ability to sustain itself photoautotrophically for several months. This unusual photosynthetic sea slug also harbors an array of undescribed bacteria, which may contribute to the long-term success of the symbiosis. Here, we utilized 16S rDNA-based metagenomic analyses to characterize the microbial diversity associated with two populations of E. chlorotica from Halifax, Nova Scotia, Canada, and from Martha's Vineyard, Massachusetts, USA. Animals were examined immediately after collection from their native environments, after being starved of their algal prey for several months, and after being bred in the laboratory (second-generation sea slugs) to characterize the effect of varying environmental and culturing conditions on the associated bacteria. Additionally, the microbiome of the algal prey, laboratory-cultured V. litorea, was analyzed to determine whether the laboratory-bred sea slugs obtained bacteria from their algal food source during development. Bacterial profiles varied between populations and among all conditions except for the F2 laboratory-bred samples, which were similar in diversity and abundance, but not to the algal microbiome. Alpha-, beta-, and gamma-proteobacteria dominated all of the samples along with Actinobacteria, Bacilli, Flavobacteria, and Sphingobacteria. Bacteria capable of polysaccharide digestion and photosynthesis, as well as putative nitrogen fixation, vitamin B(12) production, and natural product biosynthesis were associated with the sea slug and algal samples.

  6. Depression and anxiety symptoms are associated with white blood cell count and red cell distribution width: A sex-stratified analysis in a population-based study.

    PubMed

    Shafiee, Mojtaba; Tayefi, Maryam; Hassanian, Seyed Mahdi; Ghaneifar, Zahra; Parizadeh, Mohammad Reza; Avan, Amir; Rahmani, Farzad; Khorasanchi, Zahra; Azarpajouh, Mahmoud Reza; Safarian, Hamideh; Moohebati, Mohsen; Heidari-Bakavoli, Alireza; Esmaeili, Habibolah; Nematy, Mohsen; Safarian, Mohammad; Ebrahimi, Mahmoud; Ferns, Gordon A; Mokhber, Naghmeh; Ghayour-Mobarhan, Majid

    2017-10-01

    Depression and anxiety are two common mood disorders that are both linked to systemic inflammation. Increased white blood cell (WBC) count and red cell distribution width (RDW) are associated with negative clinical outcomes in a wide variety of pathological conditions. WBC is a non-specific inflammatory marker and RDW is also strongly related to other inflammatory markers. Therefore, we proposed that there might be an association between these hematological inflammatory markers and depression/anxiety symptoms. The primary objective of this study was to examine the association between depression/anxiety symptoms and hematological inflammatory markers including WBC and RDW in a large population-based study. Symptoms of depression and anxiety and a complete blood count (CBC) were measured in 9274 participants (40% males and 60% females) aged 35-65 years, enrolled in a population-based cohort (MASHAD) study in north-eastern Iran. Symptoms of depression and anxiety were evaluated using the Beck Depression and Anxiety Inventories. The mean WBC count increased with increasing severity of symptoms of depression and anxiety among men. Male participants with severe depression had significantly higher values of RDW (p<0.001); however, this relationship was less marked among women (p=0.004). In addition, men (but not women) with severe anxiety symptoms had significantly higher values of RDW (p<0.001). Moreover, there was a negative association between red blood cell (RBC) and mean corpuscular hemoglobin (MCH) and symptoms of depression/anxiety. Our results suggest that higher depression and anxiety scores are associated with an enhanced inflammatory state, as assessed by higher hematological inflammatory markers including WBC and RDW, even after adjusting for potential confounders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Association of volunteering with mental well-being: a lifecourse analysis of a national population-based longitudinal study in the UK

    PubMed Central

    Tabassum, Faiza; Mohan, John; Smith, Peter

    2016-01-01

    Objectives The association of volunteering with well-being has been found in previous research, but mostly among older people. The aim of this study was to examine the association of volunteering with mental well-being among the British population across the life course. Design British Household Panel Survey, a population-based longitudinal study. Setting UK. Participants 66 343 observations (person-years). Main outcome measures Mental well-being was measured by using the General Health Questionnaire (GHQ-12 or GHQ); high values denote high mental disorder. Four groups of volunteering participation were created: frequent (once a week), infrequent (once a month/several times a year), rare (once or less a year) and never. Multilevel linear models were used to analyse variations in mental well-being over the life course by levels of volunteering. Results When not considering age, those who engaged in volunteering regularly appeared to experience higher levels of mental well-being than those who never volunteered. To explore the association of volunteering with the GHQ across the life course, interaction terms were fitted between age and volunteering. The interactions were significant, demonstrating that these associations vary by age. The association between volunteering and well-being did not emerge during early adulthood to mid-adulthood, instead becoming apparent above the age of 40 years and continuing up to old age. Moreover, in early adulthood, the absence of engagement in voluntary activity was not related to mental well-being, but GHQ scores for this group increased sharply with age, levelling off after the age of 40 and then increasing again above the age of 70 years. The study also indicates variation in GHQ scores (65%) within individuals across time, suggesting evidence of lifecourse effects. Conclusions We conclude that volunteering may be more meaningful for mental well-being at some points of time in the life course. PMID:27503861

  8. Analysis of association between TLR-4 Asp299Gly and Thr399Ile gene polymorphisms and chronic periodontitis in a sample of south Indian population

    PubMed Central

    Reddy, Bavigadda Harish; Jayakumar, N. D.; Akula, Sreenivasa Rao; Sharma, Rupali; Kaarthikeyan, G.; Sankari

    2011-01-01

    Background: To analyze the association between TLR-4 Asp299Gly and Thr399Ile gene polymorphisms and chronic periodontitis in a sample of south Indian population. Materials and Methods: Genomic DNA was obtained from peripheral blood of 60 patients with chronic periodontitis and 60 periodontally healthy subjects. TLR-4 Asp299Gly and Thr399Ile gene polymorphisms were genotyped by a polymerase chain reaction–restriction fragment length polymorphism method. The data were analyzed by a χ2-test and by relative risk estimation. Results: Thr399Ile alleles were found in 4% of chronic periodontitis patients and in 1% of periodontally healthy subjects. The prevalence of a Thr399Ile heterozygote was found to be 5% in the chronic periodontitis group and 1.67% in the periodontally healthy group, respectively. Homozygosity for TLR-4 Thr399Ile was seen in chronic periodontitis patients only, which was 1.67%. The TLR-4 Asp299Gly gene polymorphism was not detected in either chronic periodontitis or periodontally healthy groups. Conclusion: There is no significant association between TLR-4 Thr399Ile polymorphism and chronic periodontitis in a sample of south Indian population. PMID:22368361

  9. The association between the rs11196218A/G polymorphism of the TCF7L2 gene and type 2 diabetes in the Chinese Han population: a meta-analysis

    PubMed Central

    Ma, Enting; Wang, Huili; Guo, Jing; Tian, Ruirui; Wei, Li

    2015-01-01

    Transcription factor 7-like 2 has been shown to be associated with type 2 diabetes mellitus in multiple ethnic groups in recent years. In the Chinese Han population in particular, numerous studies have evaluated the association between the rs11196218A/G polymorphism of the transcription factor 7-like 2 gene and type 2 diabetes mellitus. However, the results have been inconsistent, so we performed a meta-analysis to assess the association. Odds ratio and 95% confidence interval values were calculated using a random-effects model or a fixed-effects model based on heterogeneity analysis. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale. Subgroup analyses were conducted based on conformity with Hardy-Weinberg equilibrium in the control group as well as on other variables, such as age, sex and body mass index. Sensitivity analysis was also performed to detect heterogeneity and to assess the stability of the results. In total, 10 case-control studies comprising 7,491 cases and 12,968 controls were included in this meta-analysis. The combined analysis indicated that the rs11196218A/G polymorphism was not associated with type 2 diabetes mellitus (G vs. A, OR=1.04, 95% CI=0.97-1.13, p=0.28). The subgroup analyses also did not show any association between the rs11196218A/G polymorphism and the risk of type 2 diabetes mellitus. Furthermore, the results of the subgroup analyses indicated that the absence of an association was not influenced by age, sex or body mass index. The results of the sensitivity analysis verified the reliability and stability of this meta-analysis. In conclusion, this study indicated that there is no significant association between the rs11196218A/G polymorphism and the risk of type 2 diabetes mellitus in the Chinese Han population. PMID:26247673

  10. Association analysis of DACT1 genetic variants and gastric cancer risk in a Chinese Han population: a case–control study

    PubMed Central

    Huang, Chi; Wang, Younan; Fan, Hao; Ma, Xiang; Tang, Ran; Huan, Xiangkun; Zhu, Yi; Xu, Zekuan; Xu, Hao; Yang, Li

    2016-01-01

    Purpose Disheveled-binding antagonist of beta-catenin 1 (DACT1) is involved in tumorigenesis through influencing cell apoptosis and proliferation. We aimed to investigate the effect of three tag single-nucleotide polymorphisms (SNPs) in DACT1 (rs863091 C>T, rs17832998 C>T, and rs167481 C>T) on the occurrence of gastric cancer (GC), their association with specific clinical characteristics, and consideration of the functional relevance of GC-related SNPs. Subjects and methods In this hospital-based case–control study, the genotypes were acquired using the TaqMan-MGB method consisting of 602 cases and 602 controls. DACT1 messenger RNA level was evaluated in 76 paired tumoral and normal tissues using quantitative reverse transcription–polymerase chain reaction. Logistic regression was used to evaluate the associations among the DACT1 SNPs and GC. Results We found a significant association between the variant genotypes of rs863091 and decreased risk of GC (TT vs CC: P=0.009, adjusted odds ratio =0.34, 95% confidence interval =0.15–0.77; CT + TT vs CC: P=0.030, adjusted odds ratio =0.74, 95% confidence interval =0.57–0.97). In further stratified analyses, rs863091 variant genotypes were associated with a reduced risk of GC in younger individuals (<60 years) and males. No overall significant association with GC risk was observed in SNP rs17832998 or rs167481. Additionally, we assessed DACT1 messenger RNA levels in GC and found that DACT1 expressions of individuals carrying CT and TT genotypes were much higher than those with CC genotype. Conclusion Our findings suggest that the DACT1 rs863091 C>T polymorphism may be associated with a decreased risk of GC in the Chinese Han population and influence DACT1 expression. PMID:27729806

  11. Population-based genetic epidemiologic analysis of Chlamydia trachomatis serotypes and lack of association between ompA polymorphisms and clinical phenotypes.

    PubMed

    Millman, Kim; Black, Carolyn M; Stamm, Walter E; Jones, Robert B; Hook, Edward W; Martin, David H; Bolan, Gail; Tavaré, Simon; Dean, Deborah

    2006-03-01

    Chlamydia trachomatis is the leading cause of bacterial sexually transmitted diseases worldwide. Urogenital strains are classified into serotypes and genotypes based on the major outer membrane protein and its gene, ompA, respectively. Studies of the association of serotypes with clinical signs and symptoms have produced conflicting results while no studies have evaluated associations with ompA polymorphisms. We designed a population-based cross-sectional study of 344 men and women with urogenital chlamydial infections (excluding co-pathogen infections) presenting to clinics serving five U.S. cities from 1995 to 1997. Signs, symptoms and sequelae of chlamydial infection (mucopurulent cervicitis, vaginal or urethral discharge; dysuria; lower abdominal pain; abnormal vaginal bleeding; and pelvic inflammatory disease) were analyzed for associations with serotype and ompA polymorphisms. One hundred and fifty-three (44.5%) of 344 patients had symptoms consistent with urogenital chlamydial infection. Gender, reason for visit and city were significant independent predictors of symptom status. Men were 2.2 times more likely than women to report any symptoms (P=0.03) and 2.8 times more likely to report a urethral discharge than women were to report a vaginal discharge in adjusted analyses (P=0.007). Differences in serotype or ompA were not predictive except for an association between serotype F and pelvic inflammatory disease (P=0.046); however, the number of these cases was small. While there was no clinically prognostic value associated with serotype or ompA polymorphism for urogenital chlamydial infections except for serotype F, future studies might utilize multilocus genomic typing to identify chlamydial strains associated with clinical phenotypes.

  12. Are Sitting Occupations Associated with Increased All-Cause, Cancer, and Cardiovascular Disease Mortality Risk? A Pooled Analysis of Seven British Population Cohorts

    PubMed Central

    Stamatakis, Emmanuel; Chau, Josephine Y.; Pedisic, Zeljko; Bauman, Adrian; Macniven, Rona; Coombs, Ngaire; Hamer, Mark

    2013-01-01

    Background There is mounting evidence for associations between sedentary behaviours and adverse health outcomes, although the data on occupational sitting and mortality risk remain equivocal. The aim of this study was to determine the association between occupational sitting and cardiovascular, cancer and all-cause mortality in a pooled sample of seven British general population cohorts. Methods The sample comprised 5380 women and 5788 men in employment who were drawn from five Health Survey for England and two Scottish Health Survey cohorts. Participants were classified as reporting standing, walking or sitting in their work time and followed up over 12.9 years for mortality. Data were modelled using Cox proportional hazard regression adjusted for age, waist circumference, self-reported general health, frequency of alcohol intake, cigarette smoking, non-occupational physical activity, prevalent cardiovascular disease and cancer at baseline, psychological health, social class, and education. Results In total there were 754 all-cause deaths. In women, a standing/walking occupation was associated with lower risk of all-cause (fully adjusted hazard ratio [HR] = 0.68, 95% CI 0.52–0.89) and cancer (HR = 0.60, 95% CI 0.43–0.85) mortality, compared to sitting occupations. There were no associations in men. In analyses with combined occupational type and leisure-time physical activity, the risk of all-cause mortality was lowest in participants with non-sitting occupations and high leisure-time activity. Conclusions Sitting occupations are linked to increased risk for all-cause and cancer mortality in women only, but no such associations exist for cardiovascular mortality in men or women. PMID:24086292

  13. Are sitting occupations associated with increased all-cause, cancer, and cardiovascular disease mortality risk? A pooled analysis of seven British population cohorts.

    PubMed

    Stamatakis, Emmanuel; Chau, Josephine Y; Pedisic, Zeljko; Bauman, Adrian; Macniven, Rona; Coombs, Ngaire; Hamer, Mark

    2013-01-01

    There is mounting evidence for associations between sedentary behaviours and adverse health outcomes, although the data on occupational sitting and mortality risk remain equivocal. The aim of this study was to determine the association between occupational sitting and cardiovascular, cancer and all-cause mortality in a pooled sample of seven British general population cohorts. The sample comprised 5380 women and 5788 men in employment who were drawn from five Health Survey for England and two Scottish Health Survey cohorts. Participants were classified as reporting standing, walking or sitting in their work time and followed up over 12.9 years for mortality. Data were modelled using Cox proportional hazard regression adjusted for age, waist circumference, self-reported general health, frequency of alcohol intake, cigarette smoking, non-occupational physical activity, prevalent cardiovascular disease and cancer at baseline, psychological health, social class, and education. In total there were 754 all-cause deaths. In women, a standing/walking occupation was associated with lower risk of all-cause (fully adjusted hazard ratio [HR] = 0.68, 95% CI 0.52-0.89) and cancer (HR = 0.60, 95% CI 0.43-0.85) mortality, compared to sitting occupations. There were no associations in men. In analyses with combined occupational type and leisure-time physical activity, the risk of all-cause mortality was lowest in participants with non-sitting occupations and high leisure-time activity. Sitting occupations are linked to increased risk for all-cause and cancer mortality in women only, but no such associations exist for cardiovascular mortality in men or women.

  14. Association Between Depressive Symptoms, Multiple Dimensions of Depression, and Elder Abuse: A Cross-Sectional, Population-Based Analysis of Older Adults in Urban Chicago.

    PubMed

    Roepke-Buehler, Susan K; Simon, Melissa; Dong, XinQi

    2015-09-01

    Depression is conceptualized as both a risk factor for and a consequence of elder abuse; however, current research is equivocal. This study examined associations between elder abuse and dimensions of depressive symptoms in older adults. Participants were 10,419 older adults enrolled in theChicago Health and Aging Project (CHAP), a population-based study of older adults. Regression was used to determine the relationships between depressive symptoms, depression dimensions, and abuse variables. Depressive symptoms were consistently associated with elder abuse. Participants in the highest tertile of depressive symptoms were twice as likely to have confirmed abuse with a perpetrator (odds ratio = 2.07, 95% confidence interval = [1.21, 3.52], p = .008). Elder abuse subtypes and depression dimensions were differentially associated. These findings highlight the importance of routine depression screening in older adults as a component of abuse prevention and intervention. They also provide profiles of depressive symptoms that may more accurately characterize risk for specific types of abuse. © The Author(s) 2015.

  15. Genetic Association Analysis of Fasting and 1- and 2-Hour Glucose Tolerance Test Data Using a Generalized Index of Dissimilarity Measure for the Korean Population

    PubMed Central

    Yee, Jaeyong; Kim, Yongkang; Park, Taesung

    2016-01-01

    Glucose tolerance tests have been devised to determine the speed of blood glucose clearance. Diabetes is often tested with the standard oral glucose tolerance test (OGTT), along with fasting glucose level. However, no single test may be sufficient for the diagnosis, and the World Health Organization (WHO)/International Diabetes Federation (IDF) has suggested composite criteria. Accordingly, a single multi-class trait was constructed with three of the fasting phenotypes and 1- and 2-hour OGTT phenotypes from the Korean Association Resource (KARE) project, and the genetic association was investigated. All of the 18 possible combinations made out of the 3 sets of classification for the individual phenotypes were taken into our analysis. These were possible due to a method that was recently developed by us for estimating genomic associations using a generalized index of dissimilarity. Eight single-nucleotide polymorphisms (SNPs) that were found to have the strongest main effect are reported with the corresponding genes. Four of them conform to previous reports, located in the CDKAL1 gene, while the other 4 SNPs are new findings. Two-order interacting SNP pairs of are also presented. One pair (rs2328549 and rs6486740) has a prominent association, where the two single-nucleotide polymorphism locations are CDKAL1 and GLT1D1. The latter has not been found to have a strong main effect. New findings may result from the proper construction and analysis of a composite trait. PMID:28154509

  16. Microsatellite data analysis for population genetics.

    PubMed

    Kim, Kyung Seok; Sappington, Thomas W

    2013-01-01

    Theories and analytical tools of population genetics have been widely applied for addressing various questions in the fields of ecological genetics, conservation biology, and any context where the role of dispersal or gene flow is important. Underlying much of population genetics is the analysis of variation at selectively neutral marker loci, and microsatellites continue to be a popular choice of marker. In recent decades, software programs to estimate population genetics parameters have been developed at an increasing pace as computational science and theoretical knowledge advance. Numerous population genetics software programs are presently available to analyze microsatellite genotype data, but only a handful are commonly employed for calculating parameters such as genetic variation, genetic structure, patterns of spatial and temporal gene flow, population demography, individual population assignment, and genetic relationships within and between populations. In this chapter, we introduce statistical analyses and relevant population genetic software programs that are commonly employed in the field of population genetics and molecular ecology.

  17. Ecological analysis of the association between high-risk population parameters and HIV prevalence among pregnant women enrolled in sentinel surveillance in four Southern India states.

    PubMed

    Alary, Michel; Jayachandran, A A; Lowndes, Catherine M; Bradley, Jan; Demers, Eric; Adhikary, Rajatashuvra; Mainkar, Mandar K

    2010-02-01

    The HIV epidemic is very heterogeneous at the district level in the four Southern states of India most affected by the epidemic and where transmission is mainly heterosexual. The authors carried out an ecological study of the relationship between high-risk population parameters and HIV prevalence among pregnant women (ANC HIV prevalence). The data used in this study included: ANC HIV prevalence available from the National AIDS Control Organization (dependent variable); data on prevalence of HIV and other sexually transmitted infections among female sex workers (FSWs), their clients and high-risk men who have sex with men (HR-MSM) from studies carried out in 24 districts under Avahan; data on clients' volume reported by FSWs and on the size estimates of FSWs and HR-MSM in each district; and census data. The latter two sets of data were used to estimate the percentage of female (male) adults who are FSWs (HR-MSM). The latter was also multiplied by HIV prevalence in FSWs (HR-MSM) to obtain the percentage of HIV-positive FSWs (HR-MSM) in the adult female (male) population. Linear regression was used for statistical analyses. In univariate analyses, HIV (r=0.59, p=0.002) and HSV-2 (r=0.49, p=0.014) prevalence among FSWs and mean number of clients in the last week reported by FSWs (r=0.43, p=0.036) were significant predictors of ANC HIV prevalence. In multivariate analysis, only FSW HIV prevalence remained significant. This ecological study suggests that there is a link between HIV prevalence among FSWs and the spread of HIV to the general population in Southern India. Such an observation supports the rationale of interventions targeted at the sex industry.

  18. Ecological analysis of the association between high-risk population parameters and HIV prevalence among pregnant women enrolled in sentinel surveillance in four southern India states

    PubMed Central

    Jayachandran, A A; Lowndes, Catherine M; Bradley, Jan; Demers, Eric; Adhikary, Rajatashuvra; Mainkar, Mandar K

    2010-01-01

    Background The HIV epidemic is very heterogeneous at the district level in the four Southern states of India most affected by the epidemic and where transmission is mainly heterosexual. The authors carried out an ecological study of the relationship between high-risk population parameters and HIV prevalence among pregnant women (ANC HIV prevalence). Methods The data used in this study included: ANC HIV prevalence available from the National AIDS Control Organization (dependent variable); data on prevalence of HIV and other sexually transmitted infections among female sex workers (FSWs), their clients and high-risk men who have sex with men (HR-MSM) from studies carried out in 24 districts under Avahan; data on clients' volume reported by FSWs and on the size estimates of FSWs and HR-MSM in each district; and census data. The latter two sets of data were used to estimate the percentage of female (male) adults who are FSWs (HR-MSM). The latter was also multiplied by HIV prevalence in FSWs (HR-MSM) to obtain the percentage of HIV-positive FSWs (HR-MSM) in the adult female (male) population. Linear regression was used for statistical analyses. Results In univariate analyses, HIV (r=0.59, p=0.002) and HSV-2 (r=0.49, p=0.014) prevalence among FSWs and mean number of clients in the last week reported by FSWs (r=0.43, p=0.036) were significant predictors of ANC HIV prevalence. In multivariate analysis, only FSW HIV prevalence remained significant. Conclusions This ecological study suggests that there is a link between HIV prevalence among FSWs and the spread of HIV to the general population in Southern India. Such an observation supports the rationale of interventions targeted at the sex industry. PMID:20167724

  19. Associations of Steroid Sex Hormones and Sex Hormone-Binding Globulin With the Risk of Type 2 Diabetes in Women: A Population-Based Cohort Study and Meta-analysis.

    PubMed

    Muka, Taulant; Nano, Jana; Jaspers, Loes; Meun, Cindy; Bramer, Wichor M; Hofman, Albert; Dehghan, Abbas; Kavousi, Maryam; Laven, Joop S E; Franco, Oscar H

    2017-03-01

    It remains unclear whether endogenous sex hormones (ESH) are associated with risk of type 2 diabetes (T2D) in women. Data of 3,117 postmenopausal women participants of the Rotterdam Study were analyzed to examine whether ESH and sex hormone-binding globulin (SHBG) were associated with the risk of incident T2D. Additionally, we performed a systematic review and meta-analysis of studies assessing the prospective association of ESH and SHBG with T2D in women. During a median follow-up of 11.1 years, we identified 384 incident cases of T2D in the Rotterdam Study. No association was observed between total testosterone (TT) or bioavailable testosterone (BT) with T2D. SHBG was inversely associated with the risk of T2D, whereas total estradiol (TE) was associated with increased risk of T2D. Similarly, in the meta-analysis of 13 population-based prospective studies involving more than 1,912 incident T2D cases, low levels of SHBG and high levels of TE were associated with increased risk of T2D, whereas no associations were found for other hormones. The association of SHBG with T2D did not change by menopause status, whereas the associations of ESH and T2D were based only in postmenopausal women. SHBG and TE are independent risk factors for the development of T2D in women.

  20. Association of torture and other potentially traumatic events with mental health outcomes among populations exposed to mass conflict and displacement: a systematic review and meta-analysis.

    PubMed

    Steel, Zachary; Chey, Tien; Silove, Derrick; Marnane, Claire; Bryant, Richard A; van Ommeren, Mark

    2009-08-05

    Uncertainties continue about the roles that methodological factors and key risk factors, particularly torture and other potentially traumatic events (PTEs), play in the variation of reported prevalence rates of posttraumatic stress disorder (PTSD) and depression across epidemiologic surveys among postconflict populations worldwide. To undertake a systematic review and meta-regression of the prevalence rates of PTSD and depression in the refugee and postconflict mental health field. An initial pool of 5904 articles, identified through MEDLINE, PsycINFO and PILOTS, of surveys involving refugee, conflict-affected populations, or both, published in English-language journals between 1980 and May 2009. Surveys were limited to those of adult populations (n > or = 50) reporting PTSD prevalence, depression prevalence, or both. Excluded surveys comprised patients, war veterans, and civilian populations (nonrefugees/asylum seekers) from high-income countries exposed to terrorist attacks or involved in distal conflicts (> or = 25 years). Methodological factors (response rate, sample size and design, diagnostic method) and substantive factors (sociodemographics, place of survey, torture and other PTEs, Political Terror Scale score, residency status, time since conflict). A total of 161 articles reporting results of 181 surveys comprising 81,866 refugees and other conflict-affected persons from 40 countries were identified. Rates of reported PTSD and depression showed large intersurvey variability (0%-99% and 3%-85.5%, respectively). The unadjusted weighted prevalence rate reported across all surveys for PTSD was 30.6% (95% CI, 26.3%-35.2%) and for depression was 30.8% (95% CI, 26.3%-35.6%). Methodological factors accounted for 12.9% and 27.7% PTSD and depression, respectively. Nonrandom sampling, small sample sizes, and self-report questionnaires were associated with higher rates of mental disorder. Adjusting for methodological factors, reported torture (Delta total R(2

  1. Analysis of the prevalence of cardiovascular disease and associated risk factors for European-American and African-American populations in the state of Pennsylvania 2005-2009.

    PubMed

    Long, Yong; Gracely, Edward J; Newschaffer, Craig J; Liu, Longjian

    2013-01-01

    We examined the burden of cardiovascular disease (CVD) and its associated risk factors using statewide representative data from the Pennsylvania Behavior Risk Factors Surveillance System. The data from 35,576 subjects aged ≥ 18 years participating in the Pennsylvania Behavior Risk Factors Surveillance System in 2005, 2007, and 2009 were analyzed. The age-adjusted prevalence rates of CVD were computed. Logistic regression analysis was applied to examine associations between the risk factors and CVD prevalence, with adjustment for confounding variables. The results showed that no significant changes in the prevalence of CVD, coronary heart disease, and stroke were observed in either European Americans or African Americans from 2005 to 2009 (p >0.05). African Americans had significantly greater CVD rates than European Americans. Although smoking rates significantly decreased, several other CVD risk factors (i.e., obesity, hypertension, and hypercholesterolemia) significantly increased from 2005 to 2009 in European Americans. Similar changes were observed in African Americans, although these changes did not reach statistical significance. Logistic regression analysis indicated that African Americans had a 35% greater risk of CVD. Education level less than high school, smoking, obesity, hypertension, and diabetes were significantly and positively associated with CVD. In conclusion, no significant achievements in CVD control and risk factor reduction were observed from 2005 to 2009 in Pennsylvania. Additional aggressive control of hypertension, obesity, and diabetes for both European and African Americans must be made to reduce the burden of CVD. Published by Elsevier Inc.

  2. Non-syndromic cleft lip with or without cleft palate in Asian populations: Association analysis on three gene polymorphisms of the folate pathway.

    PubMed

    Martinelli, Marcella; Girardi, Ambra; Cura, Francesca; Nouri, Nayereh; Pinto, Valentina; Carinci, Francesco; Morselli, Paolo Giovanni; Salehi, Mansoor; Scapoli, Luca

    2016-01-01

    Orofacial clefts (OFCs) are one of the most common birth defects in humans. They are the subject of a number of investigations aimed at elucidating the bases of their complex mode of inheritance involving both genetic and environmental factors. Genes belonging to the folate pathway have been among the most studied. The aim of the investigation was to replicate previous studies reporting evidence of association between polymorphisms of folate related genes and the occurrence of non-syndromic cleft lip with or without cleft palate (NSCL/P), using three independent samples of different ancestry: from Tibet, Bangladesh and Iran, respectively. Specifically, the polymorphisms rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS, were tested. A decreased risk of NSCL/P was observed in patients presenting the C677T variant at MTHFR gene (relative risk for heterozygotes=0.53; 95% confidence interval [C.I.]=0.32-0.87). The investigated polymorphisms mapping at TCN2 and CBS genes did not provide any evidence of association. Overall, these results indicate that NSCL/P risk factors differ among populations and confirm the importance of testing putative susceptibility variants in different genetic backgrounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Multilocus family-based association analysis of seven candidate polymorphisms with essential hypertension in an african-derived semi-isolated brazilian population.

    PubMed

    Kimura, L; Angeli, C B; Auricchio, M T B M; Fernandes, G R; Pereira, A C; Vicente, J P; Pereira, T V; Mingroni-Netto, R C

    2012-01-01

    Background. It has been widely suggested that analyses considering multilocus effects would be crucial to characterize the relationship between gene variability and essential hypertension (EH). Objective. To test for the presence of multilocus effects between/among seven polymorphisms (six genes) on blood pressure-related traits in African-derived semi-isolated Brazilian populations (quilombos). Methods. Analyses were carried out using a family-based design in a sample of 652 participants (97 families). Seven variants were investigated: ACE (rs1799752), AGT (rs669), ADD2 (rs3755351), NOS3 (rs1799983), GNB3 (rs5441 and rs5443), and GRK4 (rs1801058). Sensitivity analyses were further performed under a case-control design with unrelated participants only. Results. None of the investigated variants were associated individually with both systolic and diastolic BP levels (SBP and DBP, respectively) or EH (as a binary outcome). Multifactor dimensionality reduction-based techniques revealed a marginal association of the combined effect of both GNB3 variants on DBP levels in a family-based design (P = 0.040), whereas a putative NOS3-GRK4 interaction also in relation to DBP levels was observed in the case-control design only (P = 0.004). Conclusion. Our results provide limited support for the hypothesis of multilocus effects between/among the studied variants on blood pressure in quilombos. Further larger studies are needed to validate our findings.

  4. Multilocus Family-Based Association Analysis of Seven Candidate Polymorphisms with Essential Hypertension in an African-Derived Semi-Isolated Brazilian Population

    PubMed Central

    Kimura, L.; Angeli, C. B.; Auricchio, M. T. B. M.; Fernandes, G. R.; Pereira, A. C.; Vicente, J. P.; Pereira, T. V.; Mingroni-Netto, R. C.

    2012-01-01

    Background. It has been widely suggested that analyses considering multilocus effects would be crucial to characterize the relationship between gene variability and essential hypertension (EH). Objective. To test for the presence of multilocus effects between/among seven polymorphisms (six genes) on blood pressure-related traits in African-derived semi-isolated Brazilian populations (quilombos). Methods. Analyses were carried out using a family-based design in a sample of 652 participants (97 families). Seven variants were investigated: ACE (rs1799752), AGT (rs669), ADD2 (rs3755351), NOS3 (rs1799983), GNB3 (rs5441 and rs5443), and GRK4 (rs1801058). Sensitivity analyses were further performed under a case-control design with unrelated participants only. Results. None of the investigated variants were associated individually with both systolic and diastolic BP levels (SBP and DBP, respectively) or EH (as a binary outcome). Multifactor dimensionality reduction-based techniques revealed a marginal association of the combined effect of both GNB3 variants on DBP levels in a family-based design (P = 0.040), whereas a putative NOS3-GRK4 interaction also in relation to DBP levels was observed in the case-control design only (P = 0.004). Conclusion. Our results provide limited support for the hypothesis of multilocus effects between/among the studied variants on blood pressure in quilombos. Further larger studies are needed to validate our findings. PMID:23056922

  5. Association of XPC Gene Polymorphisms with Colorectal Cancer Risk in a Southern Chinese Population: A Case-Control Study and Meta-Analysis

    PubMed Central

    Hua, Rui-Xi; Zhu, Jinhong; Jiang, Dan-Hua; Zhang, Shao-Dan; Zhang, Jiang-Bo; Xue, Wen-Qiong; Li, Xi-Zhao; Zhang, Pei-Fen; He, Jing; Jia, Wei-Hua

    2016-01-01

    Xeroderma pigmentosum group C (XPC) is a key component of the nucleotide excision repair (NER) pathway. Dysfunctional XPC protein may impair NER-mediated DNA repair capacity and further lead to genomic instability and carcinogenesis. Two common nonsynonymous polymorphisms in the XPC gene, Lys939Gln (rs2228001 A > C) and Ala499Val (rs2228000 C > T), have been investigated in various types of cancer. We genotyped these two polymorphisms in 1141 cases with histologically confirmed colorectal cancer (CRC) and 1173 healthy controls to explore their causative association with CRC susceptibility. Overall, no association was observed between these two variants and the risk of CRC. Our meta-analysis also confirmed a lack of overall association. Stratified analyses were performed by age, gender, smoking status, pack-year, drinking status, tumor sites, and Duke’s stages. We found that XPC Lys939Gln polymorphism was significantly associated with an increased CRC risk in subjects at 57 years of age or younger (adjusted odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.004–1.86, p = 0.047) and non-drinkers (adjusted OR = 1.53, 95% CI = 1.10–2.12, p = 0.011). Our results indicated that XPC Lys939Gln may be a low-penetrance CRC susceptibility polymorphism. Our findings warrant further validation. PMID:27669310

  6. A study for association and interaction analysis to metabolic syndrome and the ESR1 gene on cardiovascular autonomic neuropathy in a Chinese Han population.

    PubMed

    Zeng, Fangfang; Zhou, Linuo; Tang, Zihui

    2016-01-01

    The aim of this study was to investigate the association and interaction of metabolic syndrome (MetS) and estrogen receptor alpha 1 (ESR1) gene polymorphisms on cardiovascular autonomic neuropathy (CAN). A large-scale, population-based study was conducted to analyze the interaction of MetS and ESR1 gene polymorphisms to CAN, including a total of 1977 Chinese subjects. The most common studied single nucleotide polymorphism of ESR1 gene-rs9340799, was genotyped. Multiple logistic regression (MLR) was performed to evaluate the interaction effect of environmental variables and gene polymorphisms. Interaction on an additive scale can be calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). After controlling potential confounders, MLR showed that significant association between MetS and CAN (p < 0.001). Interestingly, we found that the participants with MetS bearing the minor allele G had an increased CAN prevalence comparing those with allele A (p = 0.045), and a positive interaction was estimated by using RETI = 0.396 (95 % CI 0.262 to 0.598), AP = 0.216 (95 % CI -0.784 to 1.216) and S = 1.906 (95 % CI 0.905 to 4.015). The present findings suggest that MetS is significantly associated with CAN and provide evidence for the hypothesis that MetS and ESR1 gene polymorphism (rs9340799) have interactive effects on CAN. ClinicalTrials gov Identifier NCT02461342.

  7. A general methodology for population analysis

    NASA Astrophysics Data System (ADS)

    Lazov, Petar; Lazov, Igor

    2014-12-01

    For a given population with N - current and M - maximum number of entities, modeled by a Birth-Death Process (BDP) with size M+1, we introduce utilization parameter ρ, ratio of the primary birth and death rates in that BDP, which, physically, determines (equilibrium) macrostates of the population, and information parameter ν, which has an interpretation as population information stiffness. The BDP, modeling the population, is in the state n, n=0,1,…,M, if N=n. In presence of these two key metrics, applying continuity law, equilibrium balance equations concerning the probability distribution pn, n=0,1,…,M, of the quantity N, pn=Prob{N=n}, in equilibrium, and conservation law, and relying on the fundamental concepts population information and population entropy, we develop a general methodology for population analysis; thereto, by definition, population entropy is uncertainty, related to the population. In this approach, what is its essential contribution, the population information consists of three basic parts: elastic (Hooke's) or absorption/emission part, synchronization or inelastic part and null part; the first two parts, which determine uniquely the null part (the null part connects them), are the two basic components of the Information Spectrum of the population. Population entropy, as mean value of population information, follows this division of the information. A given population can function in information elastic, antielastic and inelastic regime. In an information linear population, the synchronization part of the information and entropy is absent. The population size, M+1, is the third key metric in this methodology. Namely, right supposing a population with infinite size, the most of the key quantities and results for populations with finite size, emerged in this methodology, vanish.

  8. Association study between genetic variations in Axin2 gene and lung cancer risk in North Indian population: A multiple interaction analysis.

    PubMed

    Bahl, Charu; Sharma, Siddharth; Singh, Navneet; Behera, Digamber

    2017-04-01

    Wnt pathway has been implicated in the process of human carcinogenesis. Axis inhibition protein2 ( Axin2), a major scaffold protein is an antagonist of Wnt pathway and is potent to act as a tumor suppressor gene in various human cancers. Therefore, the seven polymorphic sites of Axin2 gene were analyzed, in relation to lung cancer susceptibility in North Indians. A total of 608 subjects were genotyped using PCR-RFLP technique for each polymorphic site including 303 cases and 305 controls. Further association analysis was carried out using logistic regression approach to obtain adjusted odds ratio and statistical significance. MDR and CART analysis were applied to evaluate high order interactions between the SNP's. Three out of seven studied polymorphic sites showed a strong protective effect in subjects having mutant genotype for Axin2 148 C >T and heterozygous genotype for 1365 G > A and 1712 + 19 G > T towards lung cancer risk. The other important finding was the significant association of Axin2 148 C >T in SQCC patients having variant (TT) genotype. Axin2 1712 + 19 G >T showed a decreased risk for all the histological subtypes in patients with heterozygous (GT) genotype. MDR analysis predicted a best interaction model ( Axin2 148, Axin2 2062 and Axin2 1712 +19) with maximum CVC (10/10) and minimum prediction error (0.38) along with significant permutation p-value. CART analysis gave a wide spectrum of interactive combinations which exhibited a major contribution in modulating lung cancer susceptibility. Axin2 148 and Axin2 1712 + 19 were found to play a major role in modulating lung cancer risk.

  9. Association analysis of bitter receptor genes in five isolated populations identifies a significant correlation between TAS2R43 variants and coffee liking.

    PubMed

    Pirastu, Nicola; Kooyman, Maarten; Traglia, Michela; Robino, Antonietta; Willems, Sara M; Pistis, Giorgio; d'Adamo, Pio; Amin, Najaf; d'Eustacchio, Angela; Navarini, Luciano; Sala, Cinzia; Karssen, Lennart C; van Duijn, Cornelia; Toniolo, Daniela; Gasparini, Paolo

    2014-01-01

    Coffee, one of the most popular beverages in the world, contains many different physiologically active compounds with a potential impact on people's health. Despite the recent attention given to the genetic basis of its consumption, very little has been done in understanding genes influencing coffee preference among different individuals. Given its markedly bitter taste, we decided to verify if bitter receptor genes (TAS2Rs) variants affect coffee liking. In this light, 4066 people from different parts of Europe and Central Asia filled in a field questionnaire on coffee liking. They have been consequently recruited and included in the study. Eighty-eight SNPs covering the 25 TAS2R genes were selected from the available imputed ones and used to run association analysis for coffee liking. A significant association was detected with three SNP: one synonymous and two functional variants (W35S and H212R) on the TAS2R43 gene. Both variants have been shown to greatly reduce in vitro protein activity. Surprisingly the wild type allele, which corresponds to the functional form of the protein, is associated to higher liking of coffee. Since the hTAS2R43 receptor is sensible to caffeine, we verified if the detected variants produced differences in caffeine bitter perception on a subsample of people coming from the FVG cohort. We found a significant association between differences in caffeine perception and the H212R variant but not with the W35S, which suggests that the effect of the TAS2R43 gene on coffee liking is mediated by caffeine and in particular by the H212R variant. No other significant association was found with other TAS2R genes. In conclusion, the present study opens new perspectives in the understanding of coffee liking. Further studies are needed to clarify the role of the TAS2R43 gene in coffee hedonics and to identify which other genes and pathways are involved in its genetics.

  10. Population dynamics of Vibrio spp. associated with marine sponge microcosms.

    PubMed

    Hoffmann, Maria; Fischer, Markus; Ottesen, Andrea; McCarthy, Peter J; Lopez, Jose V; Brown, Eric W; Monday, Steven R

    2010-12-01

    Vibrio is a diverse genus of marine-associated bacteria with at least 74 species and more expected as additional marine ecospheres are interrogated. This report describes a phylogenetic reconstruction of Vibrio isolates derived from one such unique ecosystem, marine sponges (Phylum Porifera) collected from depths of 150 to 1242 feet. 16S rRNA gene sequencing along with molecular typing of 16S-23S rRNA intergenic spacer regions clustered many sponge-associated Vibrio (spp) with current known species. That is, several benthic Vibrio species commensal with Porifera sponges seemed genetically linked to vibrios associated with coastal or shallow-water communities, signalling a panmictic population structure among seemingly ecologically disparate strains. Conversely, phylogenetic analysis provided evidence for at least two novel Vibrio speciation events within this specific sponge microcosm. Collectively, these findings earmark this still relatively unknown environment as a bastion of taxonomic and phylogenetic variability for the genus and probably other bacterial taxa.

  11. Adaptive Change Inferred from Genomic Population Analysis of the ST93 Epidemic Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus

    PubMed Central

    Stinear, Timothy P.; Holt, Kathryn E.; Chua, Kyra; Stepnell, Justin; Tuck, Kellie L.; Coombs, Geoffrey; Harrison, Paul Francis; Seemann, Torsten; Howden, Benjamin P.

    2014-01-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a major public health problem around the world. In Australia, ST93-IV[2B] is the dominant CA-MRSA clone and displays significantly greater virulence than other S. aureus. Here, we have examined the evolution of ST93 via genomic analysis of 12 MSSA and 44 MRSA ST93 isolates, collected from around Australia over a 17-year period. Comparative analysis revealed a core genome of 2.6 Mb, sharing greater than 99.7% nucleotide identity. The accessory genome was 0.45 Mb and comprised additional mobile DNA elements, harboring resistance to erythromycin, trimethoprim, and tetracycline. Phylogenetic inference revealed a molecular clock and suggested that a single clone of methicillin susceptible, Panton-Valentine leukocidin (PVL) positive, ST93 S. aureus likely spread from North Western Australia in the early 1970s, acquiring methicillin resistance at least twice in the mid 1990s. We also explored associations between genotype and important MRSA phenotypes including oxacillin MIC and production of exotoxins (α-hemolysin [Hla], δ-hemolysin [Hld], PSMα3, and PVL). High-level expression of Hla is a signature feature of ST93 and reduced expression in eight isolates was readily explained by mutations in the agr locus. However, subtle but significant decreases in Hld were also noted over time that coincided with decreasing oxacillin resistance and were independent of agr mutations. The evolution of ST93 S. aureus is thus associated with a reduction in both exotoxin expression and oxacillin MIC, suggesting MRSA ST93 isolates are under pressure for adaptive change. PMID:24482534

  12. Association of Statin Therapy and Risks of Cholelithiasis, Biliary Tract Diseases, and Gallbladder Procedures: Retrospective Cohort Analysis of a US Population.

    PubMed

    Martin, Donald; Schmidt, Robert; Mortensen, Eric M; Mansi, Ishak

    2016-03-01

    Gallstone disease is a leading cause of morbidity in Western countries and carries a high economic burden. Statin medications decrease hepatic cholesterol biosynthesis and may, therefore, lower the risk of cholesterol cholelithiasis by reducing the cholesterol concentration in the bile. Population-based evidence, however, is sparse. To assess the risk of gallbladder diseases among statin users compared with nonusers in an American patient cohort. We performed a retrospective cohort study of patients enrolled in the San Antonio Tricare health system using data between October 2003 and March 2012. We defined 2 groups: statin users (use for 90 days or greater) and nonusers (no prior statin). A propensity score based on 82 variables was generated to match statin users and nonusers 1:1. Outcomes included incidence of cholelithiasis, biliary tract diseases, and gallbladder procedures. A total of 43 438 patients were identified; 13 626 (31.4%) were statin users, and 29 812 (68.6%) were nonusers. We matched 6342 pairs of statin users and nonusers based on propensity score. The odds ratios (ORs) in statin users in comparison to nonusers were similar for cholelithiasis (OR = 0.86; 95% CI = 0.73, 1.02), biliary tract disease (OR = 0.85; 95% CI = 0.67-1.08), and gall bladder procedures (OR = 0.85; 95% CI = 0.69, 1.04). Statin use was not significantly associated with either an increased or decreased risk of cholelithiasis or gallbladder disease. © The Author(s) 2015.

  13. APOL1 kidney risk alleles: population genetics and disease associations.

    PubMed

    Limou, Sophie; Nelson, George W; Kopp, Jeffrey B; Winkler, Cheryl A

    2014-09-01

    APOL1 kidney disease is a unique case in the field of the genetics of common disease: 2 variants (termed G1 and G2) with high population frequency have been repeatedly associated with nondiabetic CKDs, with very strong effect size (odds ratios 3-29) in populations of sub-Saharan African descent. This review provides an update on the spectrum of APOL1 kidney disease and on the worldwide distribution of these kidney risk variants. We also summarize the proper way to run a recessive analysis on joint and independent effects of APOL1 G1 and G2 kidney risk variants. Copyright © 2014 National Kidney Foundation, Inc. All rights reserved.

  14. Effects of circadian clock genes and health-related behavior on metabolic syndrome in a Taiwanese population: Evidence from association and interaction analysis.

    PubMed

    Lin, Eugene; Kuo, Po-Hsiu; Liu, Yu-Li; Yang, Albert C; Kao, Chung-Feng; Tsai, Shih-Jen

    2017-01-01

    Increased risk of developing metabolic syndrome (MetS) has been associated with the circadian clock genes. In this study, we assessed whether 29 circadian clock-related genes (including ADCYAP1, ARNTL, ARNTL2, BHLHE40, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, GSK3B, HCRTR2, KLF10, NFIL3, NPAS2, NR1D1, NR1D2, PER1, PER2, PER3, REV1, RORA, RORB, RORC, SENP3, SERPINE1, TIMELESS, TIPIN, VIP, and VIPR2) are associated with MetS and its individual components independently and/or through complex interactions in a Taiwanese population. We also analyzed the interactions between environmental factors and these genes in influencing MetS and its individual components. A total of 3,000 Taiwanese subjects from the Taiwan Biobank were assessed in this study. Metabolic traits such as waist circumference, triglyceride, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and fasting glucose were measured. Our data showed a nominal association of MetS with several single nucleotide polymorphisms (SNPs) in five key circadian clock genes including ARNTL, GSK3B, PER3, RORA, and RORB; but none of these SNPs persisted significantly after performing Bonferroni correction. Moreover, we identified the effect of GSK3B rs2199503 on high fasting glucose (P = 0.0002). Additionally, we found interactions among the ARNTL rs10832020, GSK3B rs2199503, PER3 rs10746473, RORA rs8034880, and RORB rs972902 SNPs influenced MetS (P < 0.001 ~ P = 0.002). Finally, we investigated the influence of interactions between ARNTL rs10832020, GSK3B rs2199503, PER3 rs10746473, and RORB rs972902 with environmental factors such as alcohol consumption, smoking status, and physical activity on MetS and its individual components (P < 0.001 ~ P = 0.002). Our study indicates that circadian clock genes such as ARNTL, GSK3B, PER3, RORA, and RORB genes may contribute to the risk of MetS independently as well as through gene-gene and gene-environment interactions.

  15. Effects of circadian clock genes and health-related behavior on metabolic syndrome in a Taiwanese population: Evidence from association and interaction analysis

    PubMed Central

    Lin, Eugene; Kuo, Po-Hsiu; Liu, Yu-Li; Yang, Albert C.; Kao, Chung-Feng; Tsai, Shih-Jen

    2017-01-01

    Increased risk of developing metabolic syndrome (MetS) has been associated with the circadian clock genes. In this study, we assessed whether 29 circadian clock-related genes (including ADCYAP1, ARNTL, ARNTL2, BHLHE40, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, GSK3B, HCRTR2, KLF10, NFIL3, NPAS2, NR1D1, NR1D2, PER1, PER2, PER3, REV1, RORA, RORB, RORC, SENP3, SERPINE1, TIMELESS, TIPIN, VIP, and VIPR2) are associated with MetS and its individual components independently and/or through complex interactions in a Taiwanese population. We also analyzed the interactions between environmental factors and these genes in influencing MetS and its individual components. A total of 3,000 Taiwanese subjects from the Taiwan Biobank were assessed in this study. Metabolic traits such as waist circumference, triglyceride, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and fasting glucose were measured. Our data showed a nominal association of MetS with several single nucleotide polymorphisms (SNPs) in five key circadian clock genes including ARNTL, GSK3B, PER3, RORA, and RORB; but none of these SNPs persisted significantly after performing Bonferroni correction. Moreover, we identified the effect of GSK3B rs2199503 on high fasting glucose (P = 0.0002). Additionally, we found interactions among the ARNTL rs10832020, GSK3B rs2199503, PER3 rs10746473, RORA rs8034880, and RORB rs972902 SNPs influenced MetS (P < 0.001 ~ P = 0.002). Finally, we investigated the influence of interactions between ARNTL rs10832020, GSK3B rs2199503, PER3 rs10746473, and RORB rs972902 with environmental factors such as alcohol consumption, smoking status, and physical activity on MetS and its individual components (P < 0.001 ~ P = 0.002). Our study indicates that circadian clock genes such as ARNTL, GSK3B, PER3, RORA, and RORB genes may contribute to the risk of MetS independently as well as through gene-gene and gene-environment interactions. PMID:28296937

  16. The associations between atrial fibrillation and parameters of nutritional status assessment in the general hospital population - a cross-sectional analysis of medical documentation.

    PubMed

    Budzyński, Jacek; Anaszewicz, Marzena

    2017-01-01

    Atrial fibrillation (AF) and nutrition status abnormalities are two of the most significant epidemics in current health care. The aim of this study was to determine the relationship between the prevalence and outcome of AF, and the parameters of nutritional status among consecutive, real-life patients hospitalised in a university hospital. Analysis of the medical documentation of 4930 consecutive patients aged ≥ 18 years hospitalised for more than one day with diagnoses of cardiovascular disorders. Patients admitted with a diagnosis of AF (n = 512) compared to their counterparts without AF less frequently had an NRS-2002 score ≥ 3, normal range of body mass index (BMI), higher blood haemoglobin, and lower low density lipoprotein cholesterol (LDL-C) concentration. In logistic regression analysis, the risk of a hospitalisation due to AF was negatively related to BMI, NRS-2002 score, and the value of the difference between ideal and actual body mass. Urgent admission and having an NRS-2002 score ≥ 3 remained the only significant variables determining the risk of in-hospital death. Blood concentration of LDL-C and urgent admission were the only significant variables determining risk of 30-day rehospitalisation in the studied population. Inpatients with AF had a lower prevalence of normal body mass. Patients with an AF diagnosis had different risk factors for in-hospital death and 30-day rehospitalisation than their counterparts with diagnosis of cardiovascular diseases but without AF; however, the parameters of nutritional status played an important role in both patient groups. The obesity and cholesterol paradoxes were also observed.

  17. Microsatellite data analysis for population genetics

    USDA-ARS?s Scientific Manuscript database

    Theories and analytical tools of population genetics have been widely applied for addressing various questions in the fields of ecological genetics, conservation biology, and any context where the role of dispersal or gene flow is important. Underlying much of population genetics is the analysis of ...

  18. Association Analysis of Bitter Receptor Genes in Five Isolated Populations Identifies a Significant Correlation between TAS2R43 Variants and Coffee Liking

    PubMed Central

    Pirastu, Nicola; Kooyman, Maarten; Traglia, Michela; Robino, Antonietta; Willems, Sara M.; Pistis, Giorgio; d’Adamo, Pio; Amin, Najaf; d’Eustacchio, Angela; Navarini, Luciano; Sala, Cinzia; Karssen, Lennart C.; van Duijn, Cornelia; Toniolo, Daniela; Gasparini, Paolo

    2014-01-01

    Coffee, one of the most popular beverages in the world, contains many different physiologically active compounds with a potential impact on people’s health. Despite the recent attention given to the genetic basis of its consumption, very little has been done in understanding genes influencing coffee preference among different individuals. Given its markedly bitter taste, we decided to verify if bitter receptor genes (TAS2Rs) variants affect coffee liking. In this light, 4066 people from different parts of Europe and Central Asia filled in a field questionnaire on coffee liking. They have been consequently recruited and included in the study. Eighty-eight SNPs covering the 25 TAS2R genes were selected from the available imputed ones and used to run association analysis for coffee liking. A significant association was detected with three SNP: one synonymous and two functional variants (W35S and H212R) on the TAS2R43 gene. Both variants have been shown to greatly reduce in vitro protein activity. Surprisingly the wild type allele, which corresponds to the functional form of the protein, is associated to higher liking of coffee. Since the hTAS2R43 receptor is sensible to caffeine, we verified if the detected variants produced differences in caffeine bitter perception on a subsample of people coming from the FVG cohort. We found a significant association between differences in caffeine perception and the H212R variant but not with the W35S, which suggests that the effect of the TAS2R43 gene on coffee liking is mediated by caffeine and in particular by the H212R variant. No other significant association was found with other TAS2R genes. In conclusion, the present study opens new perspectives in the understanding of coffee liking. Further studies are needed to clarify the role of the TAS2R43 gene in coffee hedonics and to identify which other genes and pathways are involved in its genetics. PMID:24647340

  19. How Does Neighborhood Quality Moderate the Association Between Online Video Game Play and Depression? A Population-Level Analysis of Korean Students.

    PubMed

    Kim, Harris Hyun-Soo; Ahn, Sun Joo Grace

    2016-10-01

    The main objective of our study is to assess the relationship between playing online video games and mental wellbeing of adolescents based on a nationally representative sample. Data come from the Korean Children and Youth Panel Survey (KCYPS), a government-funded multiyear research project. Through a secondary analysis of W2 and W3 of data collected in 2011 and 2012, we examine the extent to which time spent playing online games is related to depression, as measured by a battery of items modeled after the abridged version of Center for Epidemiologic Studies Depression Scale Revised (CESD-R). For proper temporal ordering, the outcome variable is drawn from the latter wave (W3), whereas all time-lagged covariates are taken from the earlier wave (W2). Multilevel regression models show that more game playing is associated with greater depression. Findings also indicate that, net of individual-level variables (e.g., gender, health, family background), living in a community with more divorced families adds to adolescent depression. Finally, a cross-level interaction is observed: the positive association between game playing and depression is more pronounced in an area characterized by a lower aggregate divorce rate.

  20. Prevalence and factors associated with non-utilization of healthcare facility for childbirth in rural and urban Nigeria: Analysis of a national population-based survey.

    PubMed

    Adewuyi, Emmanuel O; Zhao, Yun; Auta, Asa; Lamichhane, Reeta

    2017-08-01

    The aim of this study was to assess the rural-urban differences in the prevalence and factors associated with non-utilization of healthcare facility for childbirth (home delivery) in Nigeria. Dataset from the Nigeria demographic and health survey, 2013, disaggregated by rural-urban residence were analyzed with appropriate adjustment for the cluster sampling design of the survey. Factors associated with home delivery were identified using multivariable logistic regression analysis. In rural and urban residence, the prevalence of home delivery were 78.3% and 38.1%, respectively ( p < 0.001). The lowest prevalence of home delivery occurred in the South-East region for rural residence (18.6%) and the South-West region for urban residence (17.9%). The North-West region had the highest prevalence of home delivery, 93.6% and 70.5% in rural and urban residence, respectively. Low maternal as well as paternal education, low antenatal attendance, being less wealthy, the practice of Islam, and living in the North-East, North-West and the South-South regions increased the likelihood of home delivery in both rural and urban residences. Whether in rural or urban residence, birth order of one decreased the likelihood of home delivery. In rural residence only, living in the North-Central region increased the chances of home delivery. In urban residence only, maternal age ⩾ 36 years decreased the likelihood of home delivery, while 'Traditionalist/other' religion and maternal age < 20 years increased it. The prevalence of home delivery was much higher in rural than urban Nigeria and the associated factors differ to varying degrees in the two residences. Future intervention efforts would need to prioritize findings in this study.

  1. Measurement of absolute copy number variation of Glutathione S-Transferase M1 gene by digital droplet PCR and association analysis in Tunisian Rheumatoid Arthritis population.

    PubMed

    Achour, Yosser; Ben Kilani, Mohamed Sahbi; Ben Hamad, Mariem; Marzouk, Sameh; Mahfoudh, Nadia; Bahloul, Zouheir; Keskes, Leila; Petit-Teixeira, Elisabeth; Maalej, Abdellatif

    2017-07-13

    The investigation of copy number variations (CNVs) analysis of candidate genes is currently an important research area in modulating human diseases. We aimed to quantify CNVs in glutathione S-transferase M1 (GSTM1) gene and determine its genetic contribution in Tunisian rheumatoid arthritis (RA) and its subsets through an innovative technique for quantification. A total of 165 RA cases and 102 healthy controls were included in the study. Using a recently powerful approach of digital droplet PCR (ddPCR), we quantified GSTM1 gene to determine the presence of no, one, or multiple copy number (CN) at high levels of sensitivity and specificity. Odds ratio and Fisher exact test were performed to estimate the association risk for GSTM1CNVs in RA. Copy number identified by ddPCR was 0, 1, and 2 copies per diploid genome. A high frequency of '0' copy was revealed with 54% in RA patients. The deletion ('0' copy) of GSTM1 was found to be a significant risk factor for anti-cyclic citrullinated peptide (anti-CCP) positive RA (OR=4.16, CI95% =[1.17-14.7]). In addition, a lack of association was found when comparing between the CNVs of RA patients and those of controls. This study highlights the powerful accuracy of ddPCR for the quantification of CNVs and suggests that the variation in the CN of GSTM1 is associated with anti-CCP positivity in RA. However, it does not indicate a specific role in the susceptibility to the disease in our Tunisian sample. © 2017 Wiley Periodicals, Inc.

  2. Discovering potential serological biomarker for chronic Hepatitis B Virus-related hepatocellular carcinoma in Chinese population by MAL-associated serum glycoproteomics analysis

    PubMed Central

    Liu, Tianhua; Liu, Denghe; Liu, Riqiang; Jiang, Hucong; Yan, Guoquan; Li, Wei; Sun, Lu; Zhang, Shu; Liu, Yinkun; Guo, Kun

    2017-01-01

    The accuracy of current biomarkers for the diagnosis of hepatocellular carcinoma (HCC), especially chronic Hepatitis B Virus (HBV)-related HCC, is limited. Recent progress in glycoproteomics has provided a novel platform for screening novel serological biomarkers of HCC. In this study, lectin affinity chromatography by Maackia amurensis lectin (MAL) and iTRAQ combined with mass spectrometric analysis were performed to enrich and identify the glycoprotein fractions in serum samples from HBV-related HCC patients and from healthy controls. Seventeen differential MAL-associated glycoproteins were identified. Among them, Galectin 3 binding protein (Gal-3BP) was selected for further evaluated by ELISA analysis and showed a high diagnostic potential of HBV-related HCC, with the AUC of 0.898 and a sensitivity, specificity and accuracy of 80.00%, 93.75% and 86.88%, respectively. Moreover, we constructed a predictive model through the combined use of serum Gal-3BP and Alpha Fetoprotein (AFP), which improved the sensitivity (from 87.5% to 95%), specificity (from 93.75% to 95%) and accuracy (from 90.63% to 95%) of diagnosing early HCC. These data suggested serum Gal-3BP level is a promising biomarker to identify HBV-related HCC and the combined use of serum Gal-3BP and AFP improves the diagnostic potential of HBV-HCC compared with AFP alone in current clinical practice. PMID:28079114

  3. Socio-Economic Differences in the Association between Self-Reported and Clinically Present Diabetes and Hypertension: Secondary Analysis of a Population-Based Cross-Sectional Study

    PubMed Central

    Tompkins, Gerald; Forrest, Lynne F.; Adams, Jean

    2015-01-01

    Background Diabetes and hypertension are key risk factors for coronary heart disease. Prevalence of both conditions is socio-economically patterned. Awareness of presence of the conditions may influence risk behaviour and use of preventative services. Our aim was to examine whether there were socio-economic differences in awareness of hypertension and diabetes in a UK population. Method Data from the Scottish Health Survey was used to compare self-reported awareness of hypertension and diabetes amongst those found on examination to have these conditions, by socioeconomic position (SEP) (measured by occupation, education and income). Odds ratios of self-reported awareness against presence, and the sensitivity, specificity and predictive value of self-reporting as a measure of the presence of the condition, were calculated. Results Presence and self-reported awareness of both conditions increased as SEP decreased, on most measures. There was only one significant difference in awareness by SEP once other factors had been taken into account. Sensitivity showed that those in the most disadvantaged groups were most likely to self-report awareness of their hypertension, and specificity showed that those in the least disadvantaged groups were most likely to self-report awareness of its absence. There were few differences of note for diabetes. Conclusion We found no consistent pattern in the associations between SEP and the presence and self-reported awareness of hypertension and diabetes amongst those with these conditions. Without evidence of differences, it is important that universal approaches continue to be applied to the identification and management of those at risk of these and other conditions that underpin cardiovascular disease. PMID:26466384

  4. Population Analysis: Communicating About Anthropometry in Context

    NASA Technical Reports Server (NTRS)

    Thaxton, Sherry; Rajulu, Sudhakar

    2009-01-01

    This slide presentation reviews the importance of communications about anthropometry and population analysis in particular for the design of aerospace systems. The difficulty of providing anthropometric accomodation an entire range of the population is reviewed, and the importance of communication of the issues with human system integration is emphasized, and the analysis of population as it applies to existing human factors methodologies is a novel way to assist with the communication. The issues of space suit design and anthropometry is reviewed as an example.

  5. Association between adiposity and blood pressure levels between the ages of 6 and 16 years. Analysis in a student population from Madrid, Spain.

    PubMed

    Marrodán Serrano, M Dolores; Cabañas Armesilla, M Dolores; Carmenate Moreno, M Margarita; González-Montero de Espinosa, Marisa; López-Ejeda, Noemí; Martínez Álvarez, Jesús R; Prado Martínez, Consuelo; Romero-Collazos, Juan F

    2013-02-01

    The increase in the incidence of hypertension in children can be attributed to the rising prevalence of obesity. The objective is to analyze the impact of overweight and the degree or distribution of adiposity on blood pressure levels in a population of Spanish schoolchildren. A cross-sectional study was carried out in 1511 schoolchildren between 6 years and 16 years of age. We measured weight, height, waist circumference, subcutaneous skinfolds, and blood pressure. Nutritional categories were established on the basis of body mass index, waist-to-height ratio, and percent body fat. According to the National High Blood Pressure Education Program Working Group, subjects whose blood pressure was above the 90th percentile of the standard normal distribution were considered to have high blood pressure. In all, 3.17% of the boys and 3.05% of the girls had high blood pressure. According to odds ratio analysis, the risk of high blood pressure increased in individuals with a body mass index indicative of obesity (7.87-fold in boys, 12.32-fold in girls), with a percent body fat>97th percentile (6.98-fold in boys, 18.51-fold in girls), or with a waist-to-height ratio ≥0.5 (10.56-fold in boys, 7.82-fold in girls). Overweight and obesity increase the risk of high blood pressure in children between 6 years and 16 years of age, although the risk level varies depending on the amount and distribution of adipose tissue. Anthropometric indicators of relative adiposity and fat distribution are especially useful in the identification of children and adolescents with high blood pressure. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  6. The association forecasting of 13 variants within seven asthma susceptibility genes on 3 serum IgE groups in Taiwanese population by integrating of adaptive neuro-fuzzy inference system (ANFIS) and classification analysis methods.

    PubMed

    Wang, Cheng-Hang; Liu, Baw-Jhiune; Wu, Lawrence Shih-Hsin

    2012-02-01

    Asthma is one of the most common chronic diseases in children. It is caused by complicated coactions between various genetic factors and environmental allergens. The study aims to integrate the concept of implementing adaptive neuro-fuzzy inference system (ANFIS) and classification analysis methods for forecasting the association of asthma susceptibility genes on 3 serum IgE groups. The ANFIS model was trained and tested with data sets obtained from 425 asthmatic subjects and 483 non-asthma subjects from the Taiwanese population. We assessed 13 single-nucleotide polymorphisms (SNPs) in seven well-known asthma susceptibility genes; firstly, the proposed ANFIS model learned to reduce input features from the 13 SNPs. And secondly, the classification will be used to classify the serum IgE groups from the simulated SNPs results. The performance of the ANFIS model, classification accuracies and the results confirmed that the integration of ANFIS and classified analysis has potential in association discovery.

  7. Identification of candidate genes associated with cell wall digestibility and eQTL (expression quantitative trait loci) analysis in a Flint x Flint maize recombinant inbred line population.

    PubMed

    Shi, Chun; Uzarowska, Anna; Ouzunova, Milena; Landbeck, Matthias; Wenzel, Gerhard; Lübberstedt, Thomas

    2007-01-18

    Cell-wall digestibility is the major target for improving the feeding value of forage maize. An understanding of the molecular basis for cell-wall digestibility is crucial towards breeding of highly digestible maize. 865 candidate ESTs for cell-wall digestibility were selected according to the analysis of expression profiles in 1) three sets of brown-midrib isogenic lines in the genetic background of inbreds 1332 (1332 and 1332 bm3), 5361 (5361 and 5361 bm3), and F2 (F2, F2 bm1, F2 bm2, and F2 bm3), 2) the contrasting extreme lines of FD (Flint x Dent, AS08 x AS 06), DD1 (Dent x Dent, AS11 x AS09), and DD2 (Dent x Dent, AS29 x AS30) mapping populations, and 3) two contrasting isogenic inbreds, AS20 and AS21. Out of those, 439 ESTs were assembled on our "Forage Quality Array", a small microarray specific for cell wall digestibility related experiments. Transcript profiles of 40 lines of a Flint x Flint population were monitored using the Forage Quality Array, which were contrasting for cell wall digestibility. Using t-tests (p < 0.01), the expression patterns of 102 ESTs were significantly different between high and low quality groups. Using interval mapping, eQTL (LOD > or = 2.4) were detected for 20% (89 of 439) of the spotted ESTs. On average, these eQTL explained 39% of the transcription variation of the corresponding ESTs. Only 26% (23 of 89) ESTs detected a single eQTL. eQTL hotspots, containing greater than 5% of the total number of eQTL, were located in chromosomal bins 1.07, 1.12, 3.05, 8.03, and 9.04, respectively. Bin 3.05 was co-localized with a cell-wall digestibility related QTL cluster. 102 candidate genes for cell-wall digestibility were validated by genetical genomics approach. Although the cDNA array highlights gene types (the tested gene and any close family members), trans-acting factors or metabolic bottlenecks seem to play the major role in controlling heritable variation of gene expression related to cell-wall digestibility, since no in silico

  8. Identification of candidate genes associated with cell wall digestibility and eQTL (expression quantitative trait loci) analysis in a Flint × Flint maize recombinant inbred line population

    PubMed Central

    Shi, Chun; Uzarowska, Anna; Ouzunova, Milena; Landbeck, Matthias; Wenzel, Gerhard; Lübberstedt, Thomas

    2007-01-01

    Background Cell-wall digestibility is the major target for improving the feeding value of forage maize. An understanding of the molecular basis for cell-wall digestibility is crucial towards breeding of highly digestible maize. Results 865 candidate ESTs for cell-wall digestibility were selected according to the analysis of expression profiles in 1) three sets of brown-midrib isogenic lines in the genetic background of inbreds 1332 (1332 and 1332 bm3), 5361 (5361 and 5361 bm3), and F2 (F2, F2 bm1, F2 bm2, and F2 bm3), 2) the contrasting extreme lines of FD (Flint × Dent, AS08 × AS 06), DD1 (Dent × Dent, AS11 × AS09), and DD2 (Dent × Dent, AS29 × AS30) mapping populations, and 3) two contrasting isogenic inbreds, AS20 and AS21. Out of those, 439 ESTs were assembled on our "Forage Quality Array", a small microarray specific for cell wall digestibility related experiments. Transcript profiles of 40 lines of a Flint × Flint population were monitored using the Forage Quality Array, which were contrasting for cell wall digestibility. Using t-tests (p < 0.01), the expression patterns of 102 ESTs were significantly different between high and low quality groups. Using interval mapping, eQTL (LOD ≥ 2.4) were detected for 20% (89 of 439) of the spotted ESTs. On average, these eQTL explained 39% of the transcription variation of the corresponding ESTs. Only 26% (23 of 89) ESTs detected a single eQTL. eQTL hotspots, containing greater than 5% of the total number of eQTL, were located in chromosomal bins 1.07, 1.12, 3.05, 8.03, and 9.04, respectively. Bin 3.05 was co-localized with a cell-wall digestibility related QTL cluster. Conclusion 102 candidate genes for cell-wall digestibility were validated by genetical genomics approach. Although the cDNA array highlights gene types (the tested gene and any close family members), trans-acting factors or metabolic bottlenecks seem to play the major role in controlling heritable variation of gene expression related to cell

  9. Lack of association between vitamin D receptor polymorphisms ApaI (rs7975232) and BsmI (rs1544410) and osteoporosis among the Han Chinese population: A meta-analysis.

    PubMed

    Yu, Meng; Chen, Guo-Qiang; Yu, Fang

    2016-12-01

    In this study, we aimed to assess the relationship between vitamin D receptor gene polymorphisms and osteoporosis in the Han Chinese population. Articles regarding associations between vitamin D receptor polymorphisms (ApaI rs7975232 and BsmI rs1544410) and osteoporosis were retrieved from databases in November 2014. Eligible studies were tested by the Hardy-Weinberg equilibrium. The odds ratio and 95% confidence interval (95% CI) were analyzed to evaluate the strength of the associations. Pooled effect estimates were derived using a fixed-effect model and a random-effect model according to the heterogeneity of the test results. A subgroup analysis by study type and a sensitivity analysis based on studies that conform to the Hardy-Weinberg equilibrium and studies with postmenopausal women as participants were performed. This meta-analysis involved 15 eligible studies including 1580 cases and 1389 controls. The pooled estimated odds ratios in the dominant and additive genetic models were 0.73 (95% CI: 0.46-1.14, p=0.17) and 1.01 (95% CI: 0.77-1.33, p=0.81), respectively, for rs7975232 and 1.01 (95% CI: 0.81-1.26, p=0.91) and 1.01 (95% CI: 0.77-1.33, p=0.92), respectively, for rs1544410. The subgroup analysis showed that regardless of the dominant or additive genetic model, the effect of pooled odds ratios for rs7975232 and rs1544410 was insignificant. The sensitivity analysis also showed that the pooled effect was not significantly changed. In conclusion, no evidence of association is apparent between polymorphisms of vitamin D receptor genes and osteoporosis risk in the Han Chinese population. Copyright © 2016. Published by Elsevier Taiwan.

  10. Genetic Architecture of a Rice Nested Association Mapping Population.

    PubMed

    Fragoso, Christopher A; Moreno, Maria; Wang, Zuoheng; Heffelfinger, Christopher; Arbelaez, Lady J; Aguirre, John A; Franco, Natalia; Romero, Luz E; Labadie, Karine; Zhao, Hongyu; Dellaporta, Stephen L; Lorieux, Mathias

    2017-06-07

    Describing the genetic diversity in the gene pool of crops will provide breeders with novel resources for varietal improvement. Nested Association Mapping (NAM) populations are uniquely suited for characterizing parental diversity through the shuffling and fixation of parental haplotypes. Here, we describe a set of 1879 rice NAM lines created through the selfing and single-seed descent of F1 hybrids derived from elite IR64 indica crossed with 10 diverse tropical japonica lines. Genotyping data indicated tropical japonica alleles were captured at every queried locus despite the presence of segregation distortion factors. Several distortion loci were mapped, both shared and unique, among the 10 populations. Using two-point and multi-point genetic map calculations, our datasets achieved the ∼1500 cM expected map size in rice. Finally, we highlighted the utility of the NAM lines for QTL mapping, including joint analysis across the 10 populations, by confirming known QTL locations for the trait days to heading. Copyright © 2017 Fragoso et al.

  11. A mixed model reduces spurious genetic associations produced by population stratification in genome-wide association studies.

    PubMed

    Shin, Jimin; Lee, Chaeyoung

    2015-04-01

    Population stratification can produce spurious genetic associations in genome-wide association studies (GWASs). Mixed model methodology has been regarded useful for correcting population stratification. This study explored statistical power and false discovery rate (FDR) with the data simulated for dichotomous traits. Empirical FDRs and powers were estimated using fixed models with and without genomic control and using mixed models with and without reflecting loci linked to the candidate marker in genetic relationships. Population stratification with admixture degree ranged from 1% to 10% resulted in inflated FDRs from the fixed model analysis without genomic control and decreased power from the fixed model analysis with genomic control (P<0.05). Meanwhile, population stratification could not change FDR and power estimates from the mixed model analyses (P>0.05). We suggest that the mixed model methodology was useful to reduce spurious genetic associations produced by population stratification in GWAS, even with a high degree of admixture (10%).

  12. An association analysis of HLA-DQB1 with narcolepsy without cataplexy and idiopathic hypersomnia with/without long sleep time in a Japanese population.

    PubMed

    Miyagawa, Taku; Toyoda, Hiromi; Kanbayashi, Takashi; Imanishi, Aya; Sagawa, Yohei; Kotorii, Nozomu; Kotorii, Tatayu; Hashizume, Yuji; Ogi, Kimihiro; Hiejima, Hiroshi; Kamei, Yuichi; Hida, Akiko; Miyamoto, Masayuki; Ikegami, Azusa; Wada, Yamato; Takami, Masanori; Fujimura, Yota; Tamura, Yoshiyuki; Omata, Naoto; Masuya, Yasuhiro; Kondo, Hideaki; Moriya, Shunpei; Furuya, Hirokazu; Kato, Mitsuhiro; Kojima, Hiroto; Kashiwase, Koichi; Saji, Hiroh; Khor, Seik-Soon; Yamasaki, Maria; Ishigooka, Jun; Wada, Yuji; Chiba, Shigeru; Yamada, Naoto; Okawa, Masako; Kuroda, Kenji; Kume, Kazuhiko; Hirata, Koichi; Uchimura, Naohisa; Shimizu, Tetsuo; Inoue, Yuichi; Honda, Yutaka; Mishima, Kazuo; Honda, Makoto; Tokunaga, Katsushi

    2015-01-01

    Narcolepsy without cataplexy (NA w/o CA) (narcolepsy type 2) is a lifelong disorder characterized by excessive daytime sleepiness and rapid eye movement (REM) sleep abnormalities, but no cataplexy. In the present study, we examined the human leukocyte antigen HLA-DQB1 in 160 Japanese patients with NA w/o CA and 1,418 control subjects. Frequencies of DQB1*06:02 were significantly higher in patients with NA w/o CA compared with controls (allele frequency: 16.6 vs. 7.8%, P=1.1×10(-7), odds ratio (OR)=2.36; carrier frequency: 31.3 vs. 14.7%, P=7.6×10(-8), OR=2.64). Distributions of HLA-DQB1 alleles other than DQB1*06:02 were compared between NA w/o CA and narcolepsy with cataplexy (NA-CA) to assess whether the genetic backgrounds of the two diseases have similarities. The distribution of the HLA-DQB1 alleles in DQB1*06:02-negative NA w/o CA was significantly different from that in NA-CA (P=5.8×10(-7)). On the other hand, the patterns of the HLA-DQB1 alleles were similar between DQB1*06:02-positive NA w/o CA and NA-CA. HLA-DQB1 analysis was also performed in 186 Japanese patients with idiopathic hypersomnia (IHS) with/without long sleep time, but no significant associations were observed.

  13. An association analysis of HLA-DQB1 with narcolepsy without cataplexy and idiopathic hypersomnia with/without long sleep time in a Japanese population

    PubMed Central

    Miyagawa, Taku; Toyoda, Hiromi; Kanbayashi, Takashi; Imanishi, Aya; Sagawa, Yohei; Kotorii, Nozomu; Kotorii, Tatayu; Hashizume, Yuji; Ogi, Kimihiro; Hiejima, Hiroshi; Kamei, Yuichi; Hida, Akiko; Miyamoto, Masayuki; Ikegami, Azusa; Wada, Yamato; Takami, Masanori; Fujimura, Yota; Tamura, Yoshiyuki; Omata, Naoto; Masuya, Yasuhiro; Kondo, Hideaki; Moriya, Shunpei; Furuya, Hirokazu; Kato, Mitsuhiro; Kojima, Hiroto; Kashiwase, Koichi; Saji, Hiroh; Khor, Seik-Soon; Yamasaki, Maria; Ishigooka, Jun; Wada, Yuji; Chiba, Shigeru; Yamada, Naoto; Okawa, Masako; Kuroda, Kenji; Kume, Kazuhiko; Hirata, Koichi; Uchimura, Naohisa; Shimizu, Tetsuo; Inoue, Yuichi; Honda, Yutaka; Mishima, Kazuo; Honda, Makoto; Tokunaga, Katsushi

    2015-01-01

    Narcolepsy without cataplexy (NA w/o CA) (narcolepsy type 2) is a lifelong disorder characterized by excessive daytime sleepiness and rapid eye movement (REM) sleep abnormalities, but no cataplexy. In the present study, we examined the human leukocyte antigen HLA-DQB1 in 160 Japanese patients with NA w/o CA and 1,418 control subjects. Frequencies of DQB1*06:02 were significantly higher in patients with NA w/o CA compared with controls (allele frequency: 16.6 vs. 7.8%, P=1.1×10−7, odds ratio (OR)=2.36; carrier frequency: 31.3 vs. 14.7%, P=7.6×10−8, OR=2.64). Distributions of HLA-DQB1 alleles other than DQB1*06:02 were compared between NA w/o CA and narcolepsy with cataplexy (NA-CA) to assess whether the genetic backgrounds of the two diseases have similarities. The distribution of the HLA-DQB1 alleles in DQB1*06:02-negative NA w/o CA was significantly different from that in NA-CA (P=5.8×10−7). On the other hand, the patterns of the HLA-DQB1 alleles were similar between DQB1*06:02-positive NA w/o CA and NA-CA. HLA-DQB1 analysis was also performed in 186 Japanese patients with idiopathic hypersomnia (IHS) with/without long sleep time, but no significant associations were observed. PMID:27081540

  14. Association between Impulsivity and Weight Status in a General Population

    PubMed Central

    Bénard, Marc; Camilleri, Géraldine M.; Etilé, Fabrice; Méjean, Caroline; Bellisle, France; Reach, Gérard; Hercberg, Serge; Péneau, Sandrine

    2017-01-01

    The objective of this study is to examine the association between impulsivity and weight status in a large sample of the adult general population in France, and the influence of gender on this relationship. A total of 11,929 men and 39,114 women participating in the NutriNet-Santé cohort were selected in this cross-sectional analysis. The Barratt Impulsiveness Scale (BIS-11) was used to assess impulsivity. Weight and height were self-reported. The association between impulsivity and BMI was estimated using logistic regressions adjusted for socio-demographic and lifestyle factors. Individuals with high impulsivity levels (BIS-11 total score >71) were more likely to be obese (Odds Ratio (OR) = 1.80, 95% Confidence Interval (CI): 1.39, 2.33 in men; OR = 1.30, 95% CI: 1.15, 1.48 in women) compared to individuals in the average range of impulsivity. The strongest associations between impulsivity and obesity were observed in men, where highly impulsive participants were more likely to be class III obese (BMI > 40 kg/m2) (OR = 3.57, 95% CI: 1.86, 6.85). This large sample analysis supports the existence of a relationship between impulsivity and weight status and the importance of psychological factors in the prevention of obesity. PMID:28257032

  15. Genome-wide association and meta-analysis in populations from Starr County, Texas, and Mexico City identify type 2 diabetes susceptibility loci and enrichment for expression quantitative trait loci in top signals

    PubMed Central

    Below, J. E.; Gamazon, E. R.; Morrison, J. V.; Konkashbaev, A.; Pluzhnikov, A.; McKeigue, P. M.; Parra, E. J.; Elbein, S. C.; Hallman, D. M.; Nicolae, D. L.; Bell, G. I.; Cruz, M.

    2013-01-01

    Aims/hypothesis We conducted genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) analyses to identify and characterise risk loci for type 2 diabetes in Mexican-Americans from Starr County, TX, USA. Method Using 1.8 million directly interrogated and imputed genotypes in 837 unrelated type 2 diabetes cases and 436 normoglycaemic controls, we conducted Armitage trend tests. To improve power in this population with high disease rates, we also performed ordinal regression including an intermediate class with impaired fasting glucose and/or glucose tolerance. These analyses were followed by meta-analysis with a study of 967 type 2 diabetes cases and 343 normoglycaemic controls from Mexico City, Mexico. Result The top signals (unadjusted p value <1×10−5) included 49 single nucleotide polymorphisms (SNPs) in eight gene regions (PER3, PARD3B, EPHA4, TOMM7, PTPRD, HNT [also known as RREB1], LOC729993 and IL34) and six intergenic regions. Among these was a missense polymorphism (rs10462020; Gly639Val) in the clock gene PER3, a system recently implicated in diabetes. We also report a second signal (minimum p value 1.52× 10−6) within PTPRD, independent of the previously implicated SNP, in a population of Han Chinese. Top meta-analysis signals included known regions HNF1A and KCNQ1. Annotation of top association signals in both studies revealed a marked excess of trans-acting eQTL in both adipose and muscle tissues. Conclusions/Interpretation In the largest study of type 2 diabetes in Mexican populations to date, we identified modest associations of novel and previously reported SNPs. In addition, in our top signals we report significant excess of SNPs that predict transcript levels in muscle and adipose tissues. PMID:21647700

  16. Population structure analysis and association mapping of seed antioxidant content in USDA cowpea (Vigna unguiculata L. Walp.) core collection using SNPs

    USDA-ARS?s Scientific Manuscript database

    Cowpea (Vigna unguiculata (L) Walp.) is an important legume and the antioxidants in cowpea seeds have been recognized as health-promoting compounds for human. The objectives of this study were to analyze the population structure of cowpea collections using single nucleotide polymorphism (SNP) and to...

  17. Association of the FABP2 Ala54Thr polymorphism with type 2 diabetes, obesity, and metabolic syndrome: a population-based case-control study and a systematic meta-analysis.

    PubMed

    Liu, Y; Wu, G; Han, L; Zhao, K; Qu, Y; Xu, A; Huang, Q

    2015-02-06

    Previous studies have reported associations between the functional FABP2 Ala54Thr (rs1799883) polymorphism and type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome in different populations with conflicting results. We investigated the association between the FABP2 Ala54Thr polymorphism and T2DM (235 cases, 431 controls), obesity (377 cases, 431 controls), and metabolic syndrome (315 cases, 323 controls) by logistic regression analysis in a Chinese study cohort recruited from Yichang, Hubei Province. We then comprehensively reviewed the association of the FABP2 Ala54Thr polymorphism with T2DM, obesity, and metabolic syndrome via meta-analysis. The strength of association was assessed by odds ratios (ORs) with 95% confidence intervals (CIs). The FABP2 Ala54Thr polymorphism was significantly associated with obesity (AT vs AA: OR = 2.633, 95%CI = 1.065-6.663, P = 0.036; TT vs AA: OR = 4.160, 95%CI = 1.609-10.757, P = 0.003) and metabolic syndrome (TT vs AA: OR = 2.273, 95%CI = 1.242-4.156, P = 0.008) by logistic regression with adjustment for covariates. However, no significant association was found between T2DM and the FABP2 Ala54Thr polymorphism. We identified 24 studies on T2DM (4517 cases, 5224 controls), 9 studies on obesity (949 cases, 2002 controls), and 6 studies on metabolic syndrome (2194 cases, 3282 controls) by literature search. The meta-analyses revealed significant associations for metabolic syndrome (T allele: OR = 1.179, 95%CI = 1.015-1.362, P = 0.031) and T2DM (T allele: OR = 1.160, 95%CI = 1.08-1.24, P < 0.001), but no association for obesity (T allele: OR = 1.069, 95%CI = 0.925-1.235, P = 0.367).

  18. Association of lymphocytic colitis and lactase deficiency in pediatric population.

    PubMed

    Sun, Jihong; Lin, Jingmei; Parashette, Kalayan; Zhang, Jianjun; Fan, Rong

    2015-02-01

    Characterized by colonic mucosa intraepithelial lymphocytosis, lymphocytic colitis is primarily an entity presented in the middle-aged to elderly patient population. Very few large series of lymphocytic colitis of childhood occurrence are available in the medical literature. Ten cases each of lymphocytic colitis and of colonic lymphocytosis of other diagnosis, all with duodenal disaccharidases analysis data, were collected from the files of our institution. The electronic medical records were reviewed and multiple variables were analyzed. The ten patients with lymphocytic colitis presented with diarrhea. Of these, three had abdominal pain. The age range was 2-18 years. Nearly all patients were Caucasian (90%) and 70% were female. Endoscopically, most had normal appearing colonic mucosa. Significant past medical history, family medical history and associated comorbidities included celiac disease, Down syndrome, juvenile arthritis and other autoimmune diseases. Interestingly, the most revealing observation was that the majority of cases (80%) were associated with lactase deficiency and, for the most part, gastrointestinal symptoms improved simply by treatment with Lactaid or avoidance of dairy products. This association is statistically significant. Our clinicopathological study indicates that the typical pediatric patient is a female Caucasian. A large of portion of the patients had associated lactase deficiency and improved on Lactaid supplement alone. Copyright © 2014 Elsevier GmbH. All rights reserved.

  19. Aggressive variants of papillary thyroid microcarcinoma are associated with extrathyroidal spread and lymph-node metastases: a population-level analysis.

    PubMed

    Kuo, Eric J; Goffredo, Paolo; Sosa, Julie A; Roman, Sanziana A

    2013-10-01

    Tall cell variant (TCV) and diffuse sclerosing variant (DSV) of papillary thyroid cancer are aggressive subtypes, for which tumors ≤1 cm have not been exclusively studied. The SEER database (1988-2009) was used to compare characteristics of TCV ≤1 cm (mTCV) and DSV ≤1 cm (mDSV) with classic papillary thyroid microcarcinoma (mPTC). Survival was analyzed with the Kaplan-Meier method and log-rank test, and risk factors for nodal metastases with chi-square analysis and binary logistic regression. There were 97 mTCV, 90 mDSV, and 18,260 mPTC patients. mTCV incidence increased by 79.9% (p=0.153) over the study period, while mDSV incidence decreased by 10.3% (p=0.315). Compared to classic mPTC, mTCV tended to be larger on average (7.1 mm vs. 5.3 mm, p<0.001), with higher rates of multifocality (47.2% vs. 34.0% respectively, p=0.018) and lymph-node examination (63.9% vs. 39.2% respectively, p<0.001), while in mDSV, nodal metastases were more frequent (57.1% vs. 33.1% respectively, p=0.007). Both aggressive variants had higher rates of extrathyroidal extension (27.8% mTCV vs. 13.3% mDSV vs. 6.1% mPTC, p<0.001). Aggressive variants also received radioactive iodine more frequently (39.2% mTCV vs. 40.0% mDSV vs. 29.1% mPTC, p<0.001). However, they were not statistically more likely to receive thyroidectomy over lobectomy compared to classic mPTC. There were no significant differences in overall and disease-specific survival between the histologies. In mTCV, after adjustment, extrathyroidal extension was independently associated with size >7 mm (odds ratio (OR) 4.4 [CI 1.5-13.6]) and nodal metastasis with multifocality (OR 5.4 [CI 1.3-23.4]) and extrathyroidal extension (OR 5.8 [CI 1.3-25.4]). No statistically significant predictors of extrathyroidal extension or nodal metastasis in mDSV were observed. Aggressive variants of mPTC tend to exhibit more aggressive pathologic characteristics than classic mPTC, but survival appears to be similar. Treatment with

  20. Genome-Wide Association Study of Schizophrenia in Japanese Population

    PubMed Central

    Yamada, Kazuo; Iwayama, Yoshimi; Hattori, Eiji; Iwamoto, Kazuya; Toyota, Tomoko; Ohnishi, Tetsuo; Ohba, Hisako; Maekawa, Motoko; Kato, Tadafumi; Yoshikawa, Takeo

    2011-01-01

    Schizophrenia is a devastating neuropsychiatric disorder with genetically complex traits. Genetic variants should explain a considerable portion of the risk for schizophrenia, and genome-wide association study (GWAS) is a potentially powerful tool for identifying the risk variants that underlie the disease. Here, we report the results of a three-stage analysis of three independent cohorts consisting of a total of 2,535 samples from Japanese and Chinese populations for searching schizophrenia susceptibility genes using a GWAS approach. Firstly, we examined 115,770 single nucleotide polymorphisms (SNPs) in 120 patient-parents trio samples from Japanese schizophrenia pedigrees. In stage II, we evaluated 1,632 SNPs (1,159 SNPs of p<0.01 and 473 SNPs of p<0.05 that located in previously reported linkage regions). The second sample consisted of 1,012 case-control samples of Japanese origin. The most significant p value was obtained for the SNP in the ELAVL2 [(embryonic lethal, abnormal vision, Drosophila)-like 2] gene located on 9p21.3 (p = 0.00087). In stage III, we scrutinized the ELAVL2 gene by genotyping gene-centric tagSNPs in the third sample set of 293 family samples (1,163 individuals) of Chinese descent and the SNP in the gene showed a nominal association with schizophrenia in Chinese population (p = 0.026). The current data in Asian population would be helpful for deciphering ethnic diversity of schizophrenia etiology. PMID:21674006

  1. -141C insertion/deletion polymorphism of the dopamine D2 receptor gene is associated with schizophrenia in Chinese Han population: Evidence from an ethnic group-specific meta-analysis.

    PubMed

    Zhao, Xiaofeng; Huang, Yinglin; Chen, Kaiyuan; Li, Duolu; Han, Chao; Kan, Quancheng

    2016-09-01

    Accumulate evidence has implicated dopamine D2 receptor gene polymorphisms in the etiology of schizophrenia. A single nucleotide polymorphism, -141C insertion/deletion (Ins/Del) (rs1799732), in the promoter region of the dopamine D2 receptor gene has been linked to schizophrenia; however, the data are inconclusive. This study investigated whether the -141C polymorphism is associated with the risk of schizophrenia in different ethnic groups by performing a meta-analysis. A total of 24 case-control studies examining the association between -141C Ins/Del polymorphism and schizophrenia were identified according to established inclusion criteria. Significant association was revealed between -141C Ins/Del polymorphism and schizophrenia risk in dominant genetic model (Ins/Ins + Ins/Del versus Del/Del) (odds ratio = 0.33, 95% confidence interval = 0.14-0.81, z = 2.41, P = 0.02) in Chinese Han but not in Caucasian, Japanese or India populations. Our results indicate that -141C Ins/Del polymorphism might be a susceptibility factor for schizophrenia in Chinese Han population.

  2. Mapping of disease-associated variants in admixed populations

    PubMed Central

    2011-01-01

    Recent developments in high-throughput genotyping and whole-genome sequencing will enhance the identification of disease loci in admixed populations. We discuss how a more refined estimation of ancestry benefits both admixture mapping and association mapping, making disease loci identification in admixed populations more powerful. High-throughput genotyping and sequencing will enable refined estimation of ancestry, thus enhancing disease loci identification in admixed populations PMID:21635713

  3. Eating Behaviour in the General Population: An Analysis of the Factor Structure of the German Version of the Three-Factor-Eating-Questionnaire (TFEQ) and Its Association with the Body Mass Index.

    PubMed

    Löffler, Antje; Luck, Tobias; Then, Francisca S; Sikorski, Claudia; Kovacs, Peter; Böttcher, Yvonne; Breitfeld, Jana; Tönjes, Anke; Horstmann, Annette; Löffler, Markus; Engel, Christoph; Thiery, Joachim; Villringer, Arno; Stumvoll, Michael; Riedel-Heller, Steffi G

    2015-01-01

    The Three-Factor-Eating-Questionnaire (TFEQ) is an established instrument to assess eating behaviour. Analysis of the TFEQ-factor structure was based on selected, convenient and clinical samples so far. Aims of this study were (I) to analyse the factor structure of the German version of the TFEQ and (II)--based on the refined factor structure--to examine the association between eating behaviour and the body mass index (BMI) in a general population sample of 3,144 middle-aged and older participants (40-79 years) of the ongoing population based cohort study of the Leipzig Research Center for Civilization Diseases (LIFE Health Study). The factor structure was examined in a split-half analysis with both explorative and confirmatory factor analysis. Associations between TFEQ-scores and BMI values were tested with multiple regression analyses controlled for age, gender, and education. We found a three factor solution for the TFEQ with an 'uncontrolled eating', a 'cognitive restraint' and an 'emotional eating' domain including 29 of the original 51 TFEQ-items. Scores of the 'uncontrolled eating domain' showed the strongest correlation with BMI values (partial r = 0.26). Subjects with scores above the median in both 'uncontrolled eating' and 'emotional eating' showed the highest BMI values (mean = 29.41 kg/m²), subjects with scores below the median in all three domains showed the lowest BMI values (mean = 25.68 kg/m²; F = 72.074, p<0.001). Our findings suggest that the TFEQ is suitable to identify subjects with specific patterns of eating behaviour that are associated with higher BMI values. Such information may help health care professionals to develop and implement more tailored interventions for overweight and obese individuals.

  4. Genetic analysis of 103 candidate genes for coronary artery disease and associated phenotypes in a founder population reveals a new association between endothelin-1 and high-density lipoprotein cholesterol.

    PubMed

    Pare, Guillaume; Serre, David; Brisson, Diane; Anand, Sonia S; Montpetit, Alexandre; Tremblay, Gerald; Engert, James C; Hudson, Thomas J; Gaudet, Daniel

    2007-04-01

    Coronary artery disease (CAD) is a major health concern in both developed and developing countries. With a heritability estimated at ~50%, there is a strong rationale to better define the genetic contribution to CAD. This project involves the analysis of 884 individuals from 142 families (with average sibships of 5.7) as well as 558 case and control subjects from the Saguenay Lac St-Jean region of northeastern Quebec, with the use of 1,536 single-nucleotide polymorphisms (SNPs) in 103 candidate genes for CAD. By use of clusters of SNPs to generate multiallelic haplotypes at candidate loci for segregation studies within families, suggestive linkage for high-density lipoprotein (HDL) cholesterol is observed on chromosome 1p36.22. Furthermore, several associations that remain significant after Bonferroni correction are observed with lipoprotein-related traits as well as plasma concentrations of adiponectin. Of note, HDL cholesterol levels are associated with an amino acid substitution (lysine/asparagine) at codon 198 (rs5370) of endothelin-1 (EDN1) in a sex-specific manner, as well as with a SNP (rs2292318) located 7.7 kb upstream of lecithin cholesterol acyl-transferase (LCAT). Whereas the other observed associations are described in the current literature, these two are new. Using an independent validation sample of 806 individuals, we confirm the EDN1 association (P<.005), whereas the LCAT association was nonsignificant (P=.12).

  5. Discovery and fine-mapping of loci associated with monounsaturated fatty acids through trans-ethnic meta-analysis in Chinese and European populations

    USDA-ARS?s Scientific Manuscript database

    Monounsaturated fatty acids (MUFAs) are unsaturated fatty acids with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels were associated with cardiometabolic disorders including cardiovascular disea...

  6. [Population and environment. Requests for interdisciplinary analysis].

    PubMed

    Tudela, F

    1991-01-01

    Serious difficulties impede interdisciplinary research involving demographers, ecologists, and other students of the environment. The 1st problem concerns definitions of the different subject areas. Demographers have focused on the dynamics of some indicators that reflect complex and heterogeneous population processes. The relative autonomy of demography as a discipline was gained through an empirical orientation reflected in the statistical treatment of causality. But the traditional demographic paradigm is insufficient for untangling the causal mechanisms underlying population dynamics. Environmental disciplines on the other hand face methodologic difficulties in transcending a strictly biological focus to incorporate aspects of cultural and social influence on ecological processes. "Human ecology", a possible meeting ground for ecological and demographic studies, is more of an ambitious program of transdisciplinary research than an independent discipline. Relations between the environment and development processes, including population aspects, are of increasing international concern. A conceptual base has developed in Latin America which emphasizes the global and structural aspects of the environment and of development styles. It has been extremely difficult to apply the entire conceptualization to the concrete environmental problems that are of current interest to both civil society and governments. It may be time to replace the umbrella term "environment", defining it in more specific, systemic, and operational terms. It is time to delimit study topics in terms of concrete problems. A good example would be the situation of Lake Chapala, the largest lake in Mexico. Damage caused to it cannot be assessed by referring to the "population explosion" or an "overall development style". Environmental, economic, and sociodemographic aspects will however necessarily enter the analysis. Fragile and unstable situations are of special interest in the study of relations

  7. Unbiased methods for population-based association studies.

    PubMed

    Devlin, B; Roeder, K; Bacanu, S A

    2001-12-01

    Large, population-based samples and large-scale genotyping are being used to evaluate disease/gene associations. A substantial drawback to such samples is the fact that population substructure can induce spurious associations between genes and disease. We review two methods, called genomic control (GC) and structured association (SA), that obviate many of the concerns about population substructure by using the features of the genomes present in the sample to correct for stratification. The GC approach exploits the fact that population substructure generates "over dispersion" of statistics used to assess association. By testing multiple polymorphisms throughout the genome, only some of which are pertinent to the disease of interest, the degree of overdispersion generated by population substructure can be estimated and taken into account. The SA approach assumes that the sampled population, although heterogeneous, is composed of subpopulations that are themselves homogeneous. By using multiple polymorphisms throughout the genome, this "latent class method" estimates the probability sampled individuals derive from each of these latent subpopulations. GC has the advantage of robustness, simplicity, and wide applicability, even to experimental designs such as DNA pooling. SA is a bit more complicated but has the advantage of greater power in some realistic settings, such as admixed populations or when association varies widely across subpopulations. It, too, is widely applicable. Both also have weaknesses, as elaborated in our review.

  8. Population viability analysis for endangered Roanoke logperch

    USGS Publications Warehouse

    Roberts, James H.; Angermeier, Paul; Anderson, Gregory B.

    2016-01-01

    A common strategy for recovering endangered species is ensuring that populations exceed the minimum viable population size (MVP), a demographic benchmark that theoretically ensures low long-term extinction risk. One method of establishing MVP is population viability analysis, a modeling technique that simulates population trajectories and forecasts extinction risk based on a series of biological, environmental, and management assumptions. Such models also help identify key uncertainties that have a large influence on extinction risk. We used stochastic count-based simulation models to explore extinction risk, MVP, and the possible benefits of alternative management strategies in populations of Roanoke logperch Percina rex, an endangered stream fish. Estimates of extinction risk were sensitive to the assumed population growth rate and model type, carrying capacity, and catastrophe regime (frequency and severity of anthropogenic fish kills), whereas demographic augmentation did little to reduce extinction risk. Under density-dependent growth, the estimated MVP for Roanoke logperch ranged from 200 to 4200 individuals, depending on the assumed severity of catastrophes. Thus, depending on the MVP threshold, anywhere from two to all five of the logperch populations we assessed were projected to be viable. Despite this uncertainty, these results help identify populations with the greatest relative extinction risk, as well as management strategies that might reduce this risk the most, such as increasing carrying capacity and reducing fish kills. Better estimates of population growth parameters and catastrophe regimes would facilitate the refinement of MVP and extinction-risk estimates, and they should be a high priority for future research on Roanoke logperch and other imperiled stream-fish species.

  9. Analysis of the mycotoxigenic fungi associated with southeastern U.S. winegrapes reveals a large population of Fusarium fujikuroi isolates producing high levels of fumonisins

    USDA-ARS?s Scientific Manuscript database

    Mycotoxins pose a serious challenge to a consistently safe food supply worldwide, and their threat is only expected to worsen with our changing climate. Species of Fusarium produce one or more of several mycotoxins, including tricothecenes, zearalenone, and fumonisins, which have been associated wi...

  10. Association of Diabetes Mellitus with a Combination of Vitamin D Deficiency and Arsenic Exposure in the Korean General Population: Analysis of 2008–2009 Korean National Health and Nutrition Examination Survey Data

    PubMed Central

    2013-01-01

    Objectives We present data from the Korean National Health and Nutritional Examination Survey (KNHANES) 2008–2009 on the combination of vitamin D deficiency and arsenic exposure on diabetes mellitus (DM) in a representative sample of the adult Korean population. Methods This study was based on data obtained from the KNHANES 2008–2009, which was conducted for 3 years (2007–2009) using a rolling sampling design that involved a complex, stratified, multistage, probability-cluster survey of a representative sample of the non-institutionalized civilian population in South Korea. Results Data analysis revealed that subjects who showed both vitamin D levels in the 1st quartile (Q) and urinary arsenic levels in the 4th Q, had a 302% increased risk of having DM, as compared with those whose vitamin D and urinary arsenic levels were in the 4th Q and 1st Q, respectively. Conclusion The present study reconfirmed an association of DM with low vitamin D levels and arsenic exposure, and further showed a combination of vitamin D deficiency and arsenic exposure on DM in the general Korean population. To the best of our knowledge, this is the first report describing a combination of vitamin D deficiency and arsenic exposure on DM. The present findings have important public health implications. PMID:24472185

  11. Leveraging Hierarchical Population Structure in Discrete Association Studies

    PubMed Central

    Carlson, Jonathan; Kadie, Carl; Mallal, Simon; Heckerman, David

    2007-01-01

    Population structure can confound the identification of correlations in biological data. Such confounding has been recognized in multiple biological disciplines, resulting in a disparate collection of proposed solutions. We examine several methods that correct for confounding on discrete data with hierarchical population structure and identify two distinct confounding processes, which we call coevolution and conditional influence. We describe these processes in terms of generative models and show that these generative models can be used to correct for the confounding effects. Finally, we apply the models to three applications: identification of escape mutations in HIV-1 in response to specific HLA-mediated immune pressure, prediction of coevolving residues in an HIV-1 peptide, and a search for genotypes that are associated with bacterial resistance traits in Arabidopsis thaliana. We show that coevolution is a better description of confounding in some applications and conditional influence is better in others. That is, we show that no single method is best for addressing all forms of confounding. Analysis tools based on these models are available on the internet as both web based applications and downloadable source code at http://atom.research.microsoft.com/bio/phylod.aspx. PMID:17611623

  12. Genetic variants associated with warfarin dosage in Kuwaiti population.

    PubMed

    John, Sumi Elsa; Antony, Dinu; Eaaswarkhanth, Muthukrishnan; Hebbar, Prashantha; Alkayal, Fadi; Tuomilehto, Jaakko; Alsmadi, Osama; Thanaraj, Thangavel Alphonse

    2017-06-01

    Assessing the distinct prevalence or absence of genetic variants associated with differential response to the anticoagulant medication of warfarin in different population groups is actively pursued by pharmacogenomics community. Populations from Arabian Peninsula are underrepresented in such studies. By way of examining exome- and genome-wide genotype data from 1395 Arab individuals in Kuwait, we report distinct occurrence of warfarin response-related variants rs12460590_A/CYP2A7, rs2108622_T/CYP4F2, rs2884737_C/VKORC1 and distinct absence of rs11150606_C/PRSS53 in Kuwaiti population. The presented results in conjunction with similar literature reports on Qatari population enhance the worldwide understanding on population-specific distributions of genetic variants associated with warfarin drug dosage.

  13. Physiogenomic analysis of the Puerto Rican population

    PubMed Central

    Ruaño, Gualberto; Duconge, Jorge; Windemuth, Andreas; Cadilla, Carmen L; Kocherla, Mohan; Villagra, David; Renta, Jessica; Holford, Theodore; Santiago-Borrero, Pedro J

    2009-01-01

    Aims Admixture in the population of the island of Puerto Rico is of general interest with regards to pharmacogenetics to develop comprehensive strategies for personalized healthcare in Latin Americans. This research was aimed at determining the frequencies of SNPs in key physiological, pharmacological and biochemical genes to infer population structure and ancestry in the Puerto Rican population. Materials & methods A noninterventional, cross-sectional, retrospective study design was implemented following a controlled, stratified-by-region, random sampling protocol. The sample was based on birthrates in each region of the island of Puerto Rico, according to the 2004 National Birth Registry. Genomic DNA samples from 100 newborns were obtained from the Puerto Rico Newborn Screening Program in dried-blood spot cards. Genotyping using a physiogenomic array was performed for 332 SNPs from 196 cardiometabolic and neuroendocrine genes. Population structure was examined using a Bayesian clustering approach as well as by allelic dissimilarity as a measure of allele sharing. Results The Puerto Rican sample was found to be broadly heterogeneous. We observed three main clusters in the population, which we hypothesize to reflect the historical admixture in the Puerto Rican population from Amerindian, African and European ancestors. We present evidence for this interpretation by comparing allele frequencies for the three clusters with those for the same SNPs available from the International HapMap project for Asian, African and European populations. Conclusion Our results demonstrate that population analysis can be performed with a physiogenomic array of cardiometabolic and neuroendocrine genes to facilitate the translation of genome diversity into personalized medicine. PMID:19374515

  14. Associations of Serum Manganese Levels with Prediabetes and Diabetes among ≥60-Year-Old Chinese Adults: A Population-Based Cross-Sectional Analysis.

    PubMed

    Wang, Xuan; Zhang, Mingyue; Lui, Guang; Chang, Hong; Zhang, Meilin; Liu, Wei; Li, Ziwei; Liu, Yixin; Huang, Guowei

    2016-08-13

    Older adults can experience glucose metabolism dysfunction, and although manganese may help regulate glucose metabolism, there is little information regarding this association among older people. This cross-sectional study included 2402 Chinese adults who were ≥60 years old in 2013 (Tianjin, China), and evaluated the associations of serum manganese with prediabetes and diabetes. Serum manganese levels were measured using inductively coupled plasma mass spectrometry. Multivariable logistic regression models were used to evaluate the sex-specific associations of manganese levels with diabetes and prediabetes after adjusting for confounding factors (age, sex, life style factors, and health status). Based on the WHO criteria, prediabetes was observed in 15.1% of men and 13.4% of women, while diabetes was observed in 30.0% of men and 34.4% of women. In the final model, the odds ratios (95% confidence interval) for prediabetes according to manganese quartile were 1.000, 0.463 (0.269-0.798), 0.639 (0.383-1.065), and 0.614 (0.365-1.031) among men and 1.000, 0.773 (0.498-1.200), 0.602 (0.382-0.947), and 0.603 (0.381-0.953) among women (p for trend = 0.134 and 0.015, respectively). The lowest prevalence of diabetes among men occurred at a moderate range of serum manganese (p < 0.05). Therefore, appropriate serum manganese levels may help prevent and control prediabetes and diabetes.

  15. Clonal evolution as detected by interphase fluorescence in situ hybridization is associated with worse overall survival in a population-based analysis of patients with chronic lymphocytic leukemia in British Columbia, Canada.

    PubMed

    Huang, Steven J; Bergin, Krystal; Smith, Adam C; Gerrie, Alina S; Bruyere, Helene; Dalal, Chinmay B; Sugioka, Daniele K; Hrynchak, Monica; Ramadan, Khaled M; Karsan, Aly; Gillan, Tanya L; Toze, Cynthia L

    2017-01-01

    This study evaluates prognostic markers as predictors of clonal evolution (CE) and assesses the impact of CE on overall survival (OS) in a population-based cohort of 159 consecutive eligible patients with chronic lymphocytic leukemia (CLL) obtained from the British Columbia Provincial CLL Database. CE was detected by interphase fluorescence in situ hybridization (FISH) in 34/159 patients (21%) with 65% of CE patients acquiring deletion 17p or 11q. CD38 positive status (≥30%) on flow cytometry predicted 2.7 times increased risk of high-risk CE (acquisition of deletion 17p or 11q) on multivariate analysis. Prior CLL therapy was not a significant predictor of CE. CE was associated with 4.1 times greater risk of death when analyzed as a time-dependent variable for OS after adjusting for age, lymphocyte count, and FISH timing. High-risk CE was associated with worse OS while acquisition of low/intermediate-risk abnormalities (trisomy 12, deletion 13q, and IGH translocation) had no difference in OS. Our study demonstrates the negative impact of CE detected by FISH on OS in this population-based cohort. These data provide support for repeating FISH testing during CLL follow-up as patients with high-risk CE have reduced survival and may require closer observation. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Associations of Serum Manganese Levels with Prediabetes and Diabetes among ≥60-Year-Old Chinese Adults: A Population-Based Cross-Sectional Analysis

    PubMed Central

    Wang, Xuan; Zhang, Mingyue; Lui, Guang; Chang, Hong; Zhang, Meilin; Liu, Wei; Li, Ziwei; Liu, Yixin; Huang, Guowei

    2016-01-01

    Older adults can experience glucose metabolism dysfunction, and although manganese may help regulate glucose metabolism, there is little information regarding this association among older people. This cross-sectional study included 2402 Chinese adults who were ≥60 years old in 2013 (Tianjin, China), and evaluated the associations of serum manganese with prediabetes and diabetes. Serum manganese levels were measured using inductively coupled plasma mass spectrometry. Multivariable logistic regression models were used to evaluate the sex-specific associations of manganese levels with diabetes and prediabetes after adjusting for confounding factors (age, sex, life style factors, and health status). Based on the WHO criteria, prediabetes was observed in 15.1% of men and 13.4% of women, while diabetes was observed in 30.0% of men and 34.4% of women. In the final model, the odds ratios (95% confidence interval) for prediabetes according to manganese quartile were 1.000, 0.463 (0.269–0.798), 0.639 (0.383–1.065), and 0.614 (0.365–1.031) among men and 1.000, 0.773 (0.498–1.200), 0.602 (0.382–0.947), and 0.603 (0.381–0.953) among women (p for trend = 0.134 and 0.015, respectively). The lowest prevalence of diabetes among men occurred at a moderate range of serum manganese (p < 0.05). Therefore, appropriate serum manganese levels may help prevent and control prediabetes and diabetes. PMID:27529280

  17. Assessing the Causality Factors in the Association between (Abdominal) Obesity and Physical Activity among the Newfoundland Population-A Mendelian Randomization Analysis.

    PubMed

    Barning, Frank; Abarin, Taraneh

    2016-01-01

    A total of 1,263 adults from Newfoundland and Labrador were studied in the research. Body mass index (BMI) and percent trunk fat (PTF) were analyzed as biomarkers for obesity. The Mendelian randomization (MR) approach with two single-nucleotide polymorphisms in the fat-mass and obesity (FTO) gene as instruments was employed to assess the causal effect. In both genders, increasing physical activity significantly reduced BMI and PTF when adjusted for age and the FTO gene. The effect of physical activity was stronger on PTF than BMI. Direct observational analyses showed significant increase in BMI/PTF when physical activity decreased. A similar association in MR analyses was not significant. The association between physical activity and BMI/PTF could be due to reversed causality or common confounding factors. Our study provides insights into the causal contributions of obesity to physical activity in adults. Health intervention strategies to increase physical activity among adults should include some other plans such as improving diet for reducing obesity.

  18. Mapping asthma-associated variants in admixed populations

    PubMed Central

    Mersha, Tesfaye B.

    2015-01-01

    Admixed populations arise when two or more previously isolated populations interbreed. Mapping asthma susceptibility loci in an admixed population using admixture mapping (AM) involves screening the genome of individuals of mixed ancestry for chromosomal regions that have a higher frequency of alleles from a parental population with higher asthma risk as compared with parental population with lower asthma risk. AM takes advantage of the admixture created in populations of mixed ancestry to identify genomic regions where an association exists between genetic ancestry and asthma (in contrast to between the genotype of the marker and asthma). The theory behind AM is that chromosomal segments of affected individuals contain a significantly higher-than-average proportion of alleles from the high-risk parental population and thus are more likely to harbor disease–associated loci. Criteria to evaluate the applicability of AM as a gene mapping approach include: (1) the prevalence of the disease differences in ancestral populations from which the admixed population was formed; (2) a measurable difference in disease-causing alleles between the parental populations; (3) reduced linkage disequilibrium (LD) between unlinked loci across chromosomes and strong LD between neighboring loci; (4) a set of markers with noticeable allele-frequency differences between parental populations that contributes to the admixed population (single nucleotide polymorphisms (SNPs) are the markers of choice because they are abundant, stable, relatively cheap to genotype, and informative with regard to the LD structure of chromosomal segments); and (5) there is an understanding of the extent of segmental chromosomal admixtures and their interactions with environmental factors. Although genome-wide association studies have contributed greatly to our understanding of the genetic components of asthma, the large and increasing degree of admixture in populations across the world create many challenges

  19. Natural populations of lactic acid bacteria associated with silage fermentation as determined by phenotype, 16S ribosomal RNA and recA gene analysis.

    PubMed

    Pang, Huili; Qin, Guangyong; Tan, Zhongfang; Li, Zongwei; Wang, Yanping; Cai, Yimin

    2011-05-01

    One hundred and fifty-six strains isolated from corn (Zea mays L.), forage paddy rice (Oryza sativa L.), sorghum (Sorghum bicolor L.) and alfalfa (Medicago sativa L.) silages prepared on dairy farms were screened, of which 110 isolates were considered to be lactic acid bacteria (LAB) according to their Gram-positive and catalase-negative characteristics and, mainly, the lactic acid metabolic products. These isolates were divided into eight groups (A-H) based on the following properties: morphological and biochemical characteristics, γ-aminobutyric acid production capacity, and 16S rRNA gene sequences. They were identified as Weissella cibaria (36.4%), Weissella confusa (9.1%), Leuconostoc citreum (5.3%), Leuconostoc lactis (4.9%), Leuconostoc pseudomesenteroides (8.0%), Lactococcus lactis subsp. lactis (4.5%), Lactobacillus paraplantarum (4.5%) and Lactobacillus plantarum (27.3%). W. cibaria and W. confusa were mainly present in corn silages, and L. plantarum was dominant on sorghum and forage paddy rice silages, while L. pseudomesenteroides, L. plantarum and L. paraplantarum were the dominant species in alfalfa silage. The corn, sorghum and forage paddy rice silages were well preserved with lower pH values and ammonia-N concentrations, but had higher lactic acid content, while the alfalfa silage had relatively poor quality with higher pH values and ammonia-N concentrations, and lower lactic acid content. The present study confirmed the diversity of LAB species inhabiting silages. It showed that the differing natural populations of LAB on these silages might influence fermentation quality. These results will enable future research on the relationship between LAB species and silage fermentation quality, and will enhance the screening of appropriate inoculants aimed at improving such quality. Copyright © 2011 Elsevier GmbH. All rights reserved.

  20. An association analysis between mitochondrial DNA content, G10398A polymorphism, HPV infection, and the prognosis of cervical cancer in the Chinese Han population.

    PubMed

    Feng, Dali; Xu, Hui; Li, Xin; Wei, Yuehua; Jiang, Huangang; Xu, Hong; Luo, Aihua; Zhou, Fuxiang

    2016-04-01

    The aim was to analyze quantitative (mitochondrial DNA (mtDNA) content) and qualitative (G10398A polymorphism) mtDNA alterations as well as human papillomavirus (HPV) infection in cervical cancer prognosis. One hundred and twenty-two cases of formalin-fixed paraffin-embedded cervical carcinoma specimens were collected from the Yichang Tumor Hospital and Zhongnan Hospital of Wuhan University in the recent 10 years together with medical records. A quantitative real-time PCR (RT-PCR) was used to determine the copy number of the mitochondrial DNA and HPV expression levels. G10398A polymorphism was determined by PCR-RFLP assay. The overall survival of patients with higher mtDNA content was significantly reduced compared with lower mtDNA content patients (P = 0.029). But there was no difference of prognosis between the mtDNA 10398 A allele and G allele. However, the Kaplan-Meier survival curve illustrated a significantly reduced overall survival in the patients with 10398A plus high mtDNA copy number compared with the other groups (P < 0.05). Although no association between HPV expression level and cervical cancer prognosis was observed, 10398A got increased mtDNA content compared with 10398G (P < 0.05) and 10398G displayed an increased HPV-positive rate compared with 10398A. Furthermore, HPV-18 and mtDNA content were positively related in the younger subgroup (≤45 years) (correlation coefficient = 0.456, P = 0.022). This study indicated that mtDNA content and HPV infection status are associated with cervical cancer prognosis. High mitochondrial DNA content plus 10398 A may be a marker of poor prognosis in cervical cancer. And mtDNA variation may potentially influence the predisposition to HPV infection and cervical carcinogenesis.

  1. Associations between inadequate sleep and obesity in the US adult population: analysis of the national health interview survey (1977-2009).

    PubMed

    Jean-Louis, Girardin; Williams, Natasha J; Sarpong, Daniel; Pandey, Abhishek; Youngstedt, Shawn; Zizi, Ferdinand; Ogedegbe, Gbenga

    2014-03-29

    Epidemiologic studies show a curvilinear relationship between inadequate sleep (< 7 or > 8 hours) and obesity (Body Mass Index > 30 kg/m2), which have enormous public health impact. Using data from the National Health Interview Survey, an ongoing nationally representative cross-sectional study of non-institutionalized US adults (≥18 years) (1977 through 2009), we examined the hypothesis that inadequate sleep is independently related to overweight/obesity, with adjustment for socio-demographic, health risk, and medical factors. Self- reported data on health risks, physician-diagnosed medical conditions, sleep duration, and body weight and height were used. Prevalence of overweight and obesity increased from 31.2% to 36.9% and 10.2% to 27.7%, respectively. Whereas prevalence of very short sleep (<5 hours) and short sleep (5-6 hours) has increased from 1.7% to 2.4% and from 19.7% to 26.7%, it decreased from 11.6% to 7.8% for long sleep. According to multivariate-adjusted multinomial regression analyses, odds of overweight and obesity associated with very short sleep and short sleep increased significantly from 1977 to 2009. Odds of overweight and obesity conferred by long sleep did not show consistent and significant increases over the years. Analyses based on aggregated data showed very short sleepers had 30% greater odds of being overweight or were twice as likely to be obese, relative to 7-8 hour sleepers. Likewise, short sleepers had 20% greater odds of being overweight or 57% greater odds of being obese. Long sleepers had 20% greater odds of being obese, but no greater odds of being overweight. Our findings support the hypothesis that prevalence of very short and short sleep has gradually increased over the last 32 years. Inadequate sleep was associated with overweight and obesity for each available year.

  2. Association of sialolithiasis with cholelithiasis: A population-based study.

    PubMed

    Hung, Shih-Han; Lin, Herng-Ching; Su, Chin-Hui; Chung, Shiu-Dong

    2016-04-01

    The purpose of this study was to evaluate the association between cholelithiasis and developing sialolithiasis using a population-based coverage database. The data for this study were sourced from the Taiwan Longitudinal Health Insurance Database. We included 745 subjects with sialolithiasis as cases and 3725 sex-matched and age-matched subjects without sialolithiasis as controls. Chi-square test revealed a significant difference in the prevalence of prior cholelithiasis between the cases and controls (8.6% vs 4.1%; p < .001). Furthermore, conditional logistic regression analysis indicated that the odds ratio (OR) of prior cholelithiasis for the cases was 2.19 (95% confidence interval [CI] = 1.62-2.98) when compared with the controls after adjusting for monthly income, geographic location, urbanization level, and tobacco use disorder. The adjusted OR of prior cholelithiasis for cases was 2.20 (95% CI = 1.46-3.33) and 2.15 (95% CI = 1.38-3.42) than controls for men and women, respectively. This study demonstrates an association between sialolithiasis and cholelithiasis. © 2015 Wiley Periodicals, Inc.

  3. Cluster analysis in phenotyping a Portuguese population.

    PubMed

    Loureiro, C C; Sa-Couto, P; Todo-Bom, A; Bousquet, J

    2015-09-03

    Unbiased cluster analysis using clinical parameters has identified asthma phenotypes. Adding inflammatory biomarkers to this analysis provided a better insight into the disease mechanisms. This approach has not yet been applied to asthmatic Portuguese patients. To identify phenotypes of asthma using cluster analysis in a Portuguese asthmatic population treated in secondary medical care. Consecutive patients with asthma were recruited from the outpatient clinic. Patients were optimally treated according to GINA guidelines and enrolled in the study. Procedures were performed according to a standard evaluation of asthma. Phenotypes were identified by cluster analysis using Ward's clustering method. Of the 72 patients enrolled, 57 had full data and were included for cluster analysis. Distribution was set in 5 clusters described as follows: cluster (C) 1, early onset mild allergic asthma; C2, moderate allergic asthma, with long evolution, female prevalence and mixed inflammation; C3, allergic brittle asthma in young females with early disease onset and no evidence of inflammation; C4, severe asthma in obese females with late disease onset, highly symptomatic despite low Th2 inflammation; C5, severe asthma with chronic airflow obstruction, late disease onset and eosinophilic inflammation. In our study population, the identified clusters were mainly coincident with other larger-scale cluster analysis. Variables such as age at disease onset, obesity, lung function, FeNO (Th2 biomarker) and disease severity were important for cluster distinction. Copyright © 2015. Published by Elsevier España, S.L.U.

  4. Associations of blood lead, cadmium, and mercury with estimated glomerular filtration rate in the Korean general population: Analysis of 2008-2010 Korean National Health and Nutrition Examination Survey data

    SciTech Connect

    Kim, Yangho; Lee, Byung-Kook

    2012-10-15

    Introduction: The objective of this study was to evaluate associations between blood lead, cadmium, and mercury levels with estimated glomerular filtration rate in a general population of South Korean adults. Methods: This was a cross-sectional study based on data obtained in the Korean National Health and Nutrition Examination Survey (KNHANES) (2008-2010). The final analytical sample consisted of 5924 participants. Estimated glomerular filtration rate (eGFR) was calculated using the MDRD Study equation as an indicator of glomerular function. Results: In multiple linear regression analysis of log2-transformed blood lead as a continuous variable on eGFR, after adjusting for covariates including cadmium and mercury, the difference in eGFR levels associated with doubling of blood lead were -2.624 mL/min per 1.73 m Superscript-Two (95% CI: -3.803 to -1.445). In multiple linear regression analysis using quartiles of blood lead as the independent variable, the difference in eGFR levels comparing participants in the highest versus the lowest quartiles of blood lead was -3.835 mL/min per 1.73 m Superscript-Two (95% CI: -5.730 to -1.939). In a multiple linear regression analysis using blood cadmium and mercury, as continuous or categorical variables, as independent variables, neither metal was a significant predictor of eGFR. Odds ratios (ORs) and 95% CI values for reduced eGFR calculated for log2-transformed blood metals and quartiles of the three metals showed similar trends after adjustment for covariates. Discussion: In this large, representative sample of South Korean adults, elevated blood lead level was consistently associated with lower eGFR levels and with the prevalence of reduced eGFR even in blood lead levels below 10 {mu}g/dL. In conclusion, elevated blood lead level was associated with lower eGFR in a Korean general population, supporting the role of lead as a risk factor for chronic kidney disease.

  5. A non-exercise testing method for estimating cardiorespiratory fitness: associations with all-cause and cardiovascular mortality in a pooled analysis of eight population-based cohorts.

    PubMed

    Stamatakis, Emmanuel; Hamer, Mark; O'Donovan, Gary; Batty, George David; Kivimaki, Mika

    2013-03-01

    Cardiorespiratory fitness (CRF) is a key predictor of chronic disease, particularly cardiovascular disease (CVD), but its assessment usually requires exercise testing which is impractical and costly in most health-care settings. Non-exercise testing cardiorespiratory fitness (NET-F)-estimating methods are a less resource-demanding alternative, but their predictive capacity for CVD and total mortality has yet to be tested. The objective of this study is to examine the association of a validated NET-F algorithm with all-cause and CVD mortality. The participants were 32,319 adults (14,650 men) aged 35-70 years who took part in eight Health Survey for England and Scottish Health Survey studies between 1994 and 2003. Non-exercise testing cardiorespiratory fitness (a metabolic equivalent of VO2max) was calculated using age, sex, body mass index (BMI), resting heart rate, and self-reported physical activity. We followed participants for mortality until 2008. Two thousand one hundred and sixty-five participants died (460 cardiovascular deaths) during a mean 9.0 [standard deviation (SD) = 3.6] year follow-up. After adjusting for potential confounders including diabetes, hypertension, smoking, social class, alcohol, and depression, a higher fitness score according to the NET-F was associated with a lower risk of mortality from all-causes (hazard ratio per SD increase in NET-F 0.85, 95% confidence interval: 0.78-0.93 in men; 0.88, 0.80-0.98 in women) and CVD (men: 0.75, 0.63-0.90; women: 0.73, 0.60-0.92). Non-exercise testing cardiorespiratory fitness had a better discriminative ability than any of its components (CVD mortality c-statistic: NET-F = 0.70-0.74; BMI = 0.45-0.59; physical activity = 0.60-0.64; resting heart rate = 0.57-0.61). The sensitivity of the NET-F algorithm to predict events occurring in the highest risk quintile was better for CVD (0.49 in both sexes) than all-cause mortality (0.44 and 0.40 for men and women, respectively). The specificity for all

  6. A non-exercise testing method for estimating cardiorespiratory fitness: associations with all-cause and cardiovascular mortality in a pooled analysis of eight population-based cohorts

    PubMed Central

    Stamatakis, Emmanuel; Hamer, Mark; O'Donovan, Gary; Batty, George David; Kivimaki, Mika

    2013-01-01

    Aims Cardiorespiratory fitness (CRF) is a key predictor of chronic disease, particularly cardiovascular disease (CVD), but its assessment usually requires exercise testing which is impractical and costly in most health-care settings. Non-exercise testing cardiorespiratory fitness (NET-F)-estimating methods are a less resource-demanding alternative, but their predictive capacity for CVD and total mortality has yet to be tested. The objective of this study is to examine the association of a validated NET-F algorithm with all-cause and CVD mortality. Methods and results The participants were 32 319 adults (14 650 men) aged 35–70 years who took part in eight Health Survey for England and Scottish Health Survey studies between 1994 and 2003. Non-exercise testing cardiorespiratory fitness (a metabolic equivalent of VO2max) was calculated using age, sex, body mass index (BMI), resting heart rate, and self-reported physical activity. We followed participants for mortality until 2008. Two thousand one hundred and sixty-five participants died (460 cardiovascular deaths) during a mean 9.0 [standard deviation (SD) = 3.6] year follow-up. After adjusting for potential confounders including diabetes, hypertension, smoking, social class, alcohol, and depression, a higher fitness score according to the NET-F was associated with a lower risk of mortality from all-causes (hazard ratio per SD increase in NET-F 0.85, 95% confidence interval: 0.78–0.93 in men; 0.88, 0.80–0.98 in women) and CVD (men: 0.75, 0.63–0.90; women: 0.73, 0.60–0.92). Non-exercise testing cardiorespiratory fitness had a better discriminative ability than any of its components (CVD mortality c-statistic: NET-F = 0.70–0.74; BMI = 0.45–0.59; physical activity = 0.60–0.64; resting heart rate = 0.57–0.61). The sensitivity of the NET-F algorithm to predict events occurring in the highest risk quintile was better for CVD (0.49 in both sexes) than all-cause mortality (0.44 and 0.40 for men and women

  7. The association between leisure-time physical activity, low HDL-cholesterol and mortality in a pooled analysis of nine population-based cohorts.

    PubMed

    O'Donovan, Gary; Stensel, David; Hamer, Mark; Stamatakis, Emmanuel

    2017-06-30

    The objective of this study was to investigate associations between leisure-time physical activity, low high-density lipoprotein cholesterol (HDL-C) and mortality. Self-reported leisure-time physical activity, HDL-C concentration, and mortality were assessed in 37,059 adults in Health Survey for England and Scottish Health Survey. Meeting physical activity guidelines was defined as ≥150 min wk(-1) of moderate-intensity activity, ≥75 min wk(-1) of vigorous-intensity activity, or equivalent combinations. Low HDL-C was defined as <1.03 mmol L(-1). Cox proportional hazard models were adjusted for age, sex, smoking, total cholesterol, systolic blood pressure, body mass index, longstanding illness, and socioeconomic status. There were 2250 deaths during 326,016 person-years of follow-up. Compared with those who met physical activity guidelines and whose HDL-C was normal (reference group), all-cause mortality risk was not elevated in those who met physical activity guidelines and whose HDL-C concentration was low (hazard ratio: 1.07; 95% confidence interval: 0.75, 1.53). Compared with the reference group, all-cause mortality risk was elevated in those who did not meet physical activity guidelines and whose HDL-C was normal (1.37; 1.16, 1.61), and in those who did not meet physical activity guidelines and whose HDL-C was low (1.65; 1.37, 1.98). Cardiovascular disease mortality hazard ratios were similar, although confidence intervals were wider. There was no statistically significant evidence of biological interaction between physical inactivity and low HDL-C. This novel study supports the notion that leisure-time physical activity be recommended in those with low HDL-C concentration who may be resistant to the HDL-raising effect of exercise training.

  8. Bacterial associations reveal spatial population dynamics in Anopheles gambiae mosquitoes

    PubMed Central

    Buck, Moritz; Nilsson, Louise K. J.; Brunius, Carl; Dabiré, Roch K.; Hopkins, Richard; Terenius, Olle

    2016-01-01

    The intolerable burden of malaria has for too long plagued humanity and the prospect of eradicating malaria is an optimistic, but reachable, target in the 21st century. However, extensive knowledge is needed about the spatial structure of mosquito populations in order to develop effective interventions against malaria transmission. We hypothesized that the microbiota associated with a mosquito reflects acquisition of bacteria in different environments. By analyzing the whole-body bacterial flora of An. gambiae mosquitoes from Burkina Faso by 16 S amplicon sequencing, we found that the different environments gave each mosquito a specific bacterial profile. In addition, the bacterial profiles provided precise and predicting information on the spatial dynamics of the mosquito population as a whole and showed that the mosquitoes formed clear local populations within a meta-population network. We believe that using microbiotas as proxies for population structures will greatly aid improving the performance of vector interventions around the world. PMID:26960555

  9. Association mapping in an elite maize breeding population.

    PubMed

    Liu, Wenxin; Gowda, Manje; Steinhoff, Jana; Maurer, Hans Peter; Würschum, Tobias; Longin, Carl Friedrich Horst; Cossic, Frédéric; Reif, Jochen Christoph

    2011-09-01

    Association mapping (AM) is a powerful approach to dissect the genetic architecture of quantitative traits. The main goal of our study was to empirically compare several statistical methods of AM using data of an elite maize breeding program with respect to QTL detection power and possibility to correct for population stratification. These models were based on the inclusion of cofactors (Model A), cofactors and population effect (Model B), and SNP effects nested within populations (Model C). A total of 930 testcross progenies of an elite maize breeding population were field-evaluated for grain yield and grain moisture in multi-location trials and fingerprinted with 425 SNP markers. For grain yield, population stratification was effectively controlled by Model A. For grain moisture with a high ratio of variance among versus within populations, Model B should be applied in order to avoid potential false positives. Model C revealed large differences among allele substitution effects for trait-associated SNPs across multiple plant breeding populations. This heterogeneous SNP allele substitution effects have a severe impact for genomic selection studies, where SNP effects are often assumed to be independent of the genetic background.

  10. Population genomic footprints of selection and associations with climate in natural populations of Arabidopsis halleri from the Alps

    PubMed Central

    Fischer, Martin C; Rellstab, Christian; Tedder, Andrew; Zoller, Stefan; Gugerli, Felix; Shimizu, Kentaro K; Holderegger, Rolf; Widmer, Alex

    2013-01-01

    Natural genetic variation is essential for the adaptation of organisms to their local environment and to changing environmental conditions. Here, we examine genomewide patterns of nucleotide variation in natural populations of the outcrossing herb Arabidopsis halleri and associations with climatic variation among populations in the Alps. Using a pooled population sequencing (Pool-Seq) approach, we discovered more than two million SNPs in five natural populations and identified highly differentiated genomic regions and SNPs using FST-based analyses. We tested only the most strongly differentiated SNPs for associations with a nonredundant set of environmental factors using partial Mantel tests to identify topo-climatic factors that may underlie the observed footprints of selection. Possible functions of genes showing signatures of selection were identified by Gene Ontology analysis. We found 175 genes to be highly associated with one or more of the five tested topo-climatic factors. Of these, 23.4% had unknown functions. Genetic variation in four candidate genes was strongly associated with site water balance and solar radiation, and functional annotations were congruent with these environmental factors. Our results provide a genomewide perspective on the distribution of adaptive genetic variation in natural plant populations from a highly diverse and heterogeneous alpine environment. PMID:24102711

  11. An inbreeding model of associative overdominance during a population bottleneck.

    PubMed Central

    Bierne, N; Tsitrone, A; David, P

    2000-01-01

    Associative overdominance, the fitness difference between heterozygotes and homozygotes at a neutral locus, is classically described using two categories of models: linkage disequilibrium in small populations or identity disequilibrium in infinite, partially selfing populations. In both cases, only equilibrium situations have been considered. In the present study, associative overdominance is related to the distribution of individual inbreeding levels (i.e., genomic autozygosity). Our model integrates the effects of physical linkage and variation in inbreeding history among individual pedigrees. Hence, linkage and identity disequilibrium, traditionally presented as alternatives, are summarized within a single framework. This allows studying nonequilibrium situations in which both occur simultaneously. The model is applied to the case of an infinite population undergoing a sustained population bottleneck. The effects of bottleneck size, mating system, marker gene diversity, deleterious genomic mutation parameters, and physical linkage are evaluated. Bottlenecks transiently generate much larger associative overdominance than observed in equilibrium finite populations and represent a plausible explanation of empirical results obtained, for instance, in marine species. Moreover, the main origin of associative overdominance is random variation in individual inbreeding whereas physical linkage has little effect. PMID:10924490

  12. Incorporating landscape stochasticity into population viability analysis.

    PubMed

    Chisholm, Ryan A; Wintle, Brendan A

    2007-03-01

    The importance of incorporating landscape dynamics into population viability analysis (PVA) has previously been acknowledged, but the need to repeat the landscape generation process to encapsulate landscape stochasticity in model outputs has largely been overlooked. Reasons for this are that (1) there is presently no means for quantifying the relative effects of landscape stochasticity and population stochasticity on model outputs, and therefore no means for determining how to allocate simulation time optimally between the two; and (2) the process of generating multiple landscapes to incorporate landscape stochasticity is tedious and user-intensive with current PVA software. Here we demonstrate that landscape stochasticity can be an important source of variance in model outputs. We solve the technical problems with incorporating landscape stochasticity by deriving a formula that gives the optimal ratio of population simulations to landscape simulations for a given model, and by providing a computer program that incorporates the formula and automates multiple landscape generation in a dynamic landscape metapopulation (DLMP) model. Using a case study of a bird population, we produce estimates of DLMP model output parameters that are up to four times more precise than those estimated from a single landscape in the same amount of total simulation time. We use the DLMP modeling software RAMAS Landscape to run the landscape and metapopulation models, though our method is general and could be applied to any PVA platform. The results of this study should motivate DLMP modelers to consider landscape stochasticity in their analyses.

  13. A Nonparametric Regression Approach to Control for Population Stratification in Rare Variant Association Studies.

    PubMed

    Sha, Qiuying; Zhang, Kui; Zhang, Shuanglin

    2016-11-18

    Recently, there is increasing interest to detect associations between rare variants and complex traits. Rare variant association studies usually need large sample sizes due to the rarity of the variants, and large sample sizes typically require combining information from different geographic locations within and across countries. Although several statistical methods have been developed to control for population stratification in common variant association studies, these methods are not necessarily controlling for population stratification in rare variant association studies. Thus, new statistical methods that can control for population stratification in rare variant association studies are needed. In this article, we propose a principal component based nonparametric regression (PC-nonp) approach to control for population stratification in rare variant association studies. Our simulations show that the proposed PC-nonp can control for population stratification well in all scenarios, while existing methods cannot control for population stratification at least in some scenarios. Simulations also show that PC-nonp's robustness to population stratification will not reduce power. Furthermore, we illustrate our proposed method by using whole genome sequencing data from genetic analysis workshop 18 (GAW18).

  14. A Nonparametric Regression Approach to Control for Population Stratification in Rare Variant Association Studies

    PubMed Central

    Sha, Qiuying; Zhang, Kui; Zhang, Shuanglin

    2016-01-01

    Recently, there is increasing interest to detect associations between rare variants and complex traits. Rare variant association studies usually need large sample sizes due to the rarity of the variants, and large sample sizes typically require combining information from different geographic locations within and across countries. Although several statistical methods have been developed to control for population stratification in common variant association studies, these methods are not necessarily controlling for population stratification in rare variant association studies. Thus, new statistical methods that can control for population stratification in rare variant association studies are needed. In this article, we propose a principal component based nonparametric regression (PC-nonp) approach to control for population stratification in rare variant association studies. Our simulations show that the proposed PC-nonp can control for population stratification well in all scenarios, while existing methods cannot control for population stratification at least in some scenarios. Simulations also show that PC-nonp’s robustness to population stratification will not reduce power. Furthermore, we illustrate our proposed method by using whole genome sequencing data from genetic analysis workshop 18 (GAW18). PMID:27857226

  15. Phenotypic assessments of peanut nested association mapping (NAM) populations

    USDA-ARS?s Scientific Manuscript database

    Nested association mapping (NAM) is a valuable innovation and multi-parental mapping population strategy in peanut genetics which increases the power to map quantitative trait loci and assists in extending the gene pool of elite peanut lines. In the peanut research community, two structured mapping ...

  16. Genetic characterization of the soybean Nested Association Mapping (NAM) population

    USDA-ARS?s Scientific Manuscript database

    A population of nested association mapping (NAM) families can be a valuable resource to a research community. A set of NAM families were developed by crossing 40 diverse soybean genotypes to the common hub cultivar IA 3023. The 41 parents were sequenced with next generation sequencing for single nuc...

  17. There are Two Populations of Energetic Electrons Associated with CMEs

    NASA Astrophysics Data System (ADS)

    Haggerty, D. K.; Roelof, E. C.

    2001-05-01

    The time histories of electron impulsive beam events (40-300 keV, 0.4associated with such electron events [Simnett, Roelof, and Haggerty, this Conference]. We have performed a detailed statistical analysis of the timing between the electron injection [{it Roelof and Haggerty}, this Conference] and the peak emission of type III bursts measured by WIND/WAVES at 14 MHz and 2 MHz (corresponding to solar radii of ~2.5 and ~5, respectively). We almost always found a type III burst closely associated with the electron beams. However, the average time difference between type III maxima at 14 MHz and 2 MHz was ~90 s. Since a 1 keV electron travels 1 Rs in 37s, the time difference of 90s for transit over ~2.5 Rs implies that 1 keV is the mean energy of the exciter beam in the high corona. However, we find that the 40-300keV beam electrons at ACE are injected on average about 11 min after the typeIII burst at 14 MHz. We almost never see 40-300 keV electron injections simultaneous with the solar type III bursts. Therefore the ~1 keV electron populations generating the solar type III bursts must have a low intensity and/or a very soft spectrum compared to the 40-300 keV electron events, and the near-relativistic electrons must be accelerated/injected on average some 11 min later. We note that a shock moving at 1000 km/s moves one solar radius in 12 minutes. Hence, if the prompt type III emission is associated with the launch of a shock, it is reasonable that the near-relativistic electrons could be accelerated by such a shock moving out through the corona. This is also consistent with the associations found with CMEs [Simnett, Roelof, and Haggerty

  18. Population Viability Analysis of Riverine Fishes

    SciTech Connect

    Bates, P.; Chandler, J.; Jager, H.I.; Lepla, K.; Van Winkle, W.

    1999-04-12

    Many utilities face conflkts between two goals: cost-efficient hydropower generation and protecting riverine fishes. Research to develop ecological simulation tools that can evaluate alternative mitigation strategies in terms of their benefits to fish populations is vital to informed decision-making. In this paper, we describe our approach to population viability analysis of riverine fishes in general and Snake River white sturgeon in particular. We are finding that the individual-based modeling approach used in previous in-stream flow applications is well suited to addressing questions about the viability of species of concern for several reasons. Chief among these are: (1) the abiIity to represent the effects of individual variation in life history characteristics on predicted population viabili~, (2) the flexibili~ needed to quanti~ the ecological benefits of alternative flow management options by representing spatial and temporal variation in flow and temperaturty and (3) the flexibility needed to quantifi the ecological benefits of non-flow related manipulations (i.e., passage, screening and hatchery supplementation).

  19. Genetic variants in autophagy associated genes are associated with DNA damage levels in Chinese population.

    PubMed

    Li, Zhihua; Xin, Junyi; Chen, Weihong; Liu, Jia; Zhu, Meng; Zhao, Congwen; Yuan, Jing; Jin, Guangfu; Ma, Hongxia; Du, Jiangbo; Hu, Zhibin; Wu, Tangchun; Shen, Hongbing; Dai, Juncheng; Yu, Hao

    2017-08-30

    Autophagy associated genes (ATGs) played an important role in the repair process of DNA damage and decreased autophagy may weaken the repair process and aggravate DNA damage. Based on this, we hypothesized that DNA damage levels might be modified by genetic variants in autophagy associated genes. In order to validate our hypothesis, 307 subjects were recruited from three different cities (Zhuhai, Wuhan and Tianjin) in China. Demographic data, individual 24-h PM2.5 exposure and peripheral blood DNA damage levels were also detected. Seven potentially functional polymorphisms in four essential autophagy associated genes (ATG5, ATG7, ATG8 and ATG13) were screened to evaluate the relationship between the polymorphisms of autophagy associated genes and DNA damage levels. This association was assessed by using multivariable linear regression model, age, sex, smoke and PM2.5 exposure levels were adjusted in each city. We found that rs12599322 in ATG8 (A>G, β=0.263, 95% CI: 0.108-0.419, P=8.98×10(-4)) and rs7484002 in ATG13 (A>G, β=0.396, 95% CI: 0.085-0.708, P=0.013) were significantly associated with higher DNA damage levels. Furthermore, functional annotations showed that both rs12599322 and rs7484002 located at transcription factor binding sites (TFBS), indicating that they could regulate the expression of related genes through TF regulation. Following allelic trend analysis revealed that the DNA damage levels were significantly aggravated with the increasing number of risk variants in autophagy associated genes (P for trend: 8.09×10(-5)). Our findings suggested that the polymorphisms in ATGs may influence DNA damage levels in one of the Chinese population. Copyright © 2017. Published by Elsevier B.V.

  20. Prevalence of Diabetes and Associated Factors in the Uyghur and Han Population in Xinjiang, China

    PubMed Central

    Gong, Haiying; Pa, Lize; Wang, Ke; Mu, Hebuli; Dong, Fen; Ya, Shengjiang; Xu, Guodong; Tao, Ning; Pan, Li; Wang, Bin; Shan, Guangliang

    2015-01-01

    Objective: To estimate the prevalence of diabetes and identify risk factors in the Uyghur and Han population in Xinjiang, China. Methods: A cross-sectional study in urban and rural areas in Xinjiang, including 2863 members of the Uyghur population and 3060 of the Han population aged 20 to 80 years, was conducted from June 2013 to August 2013. Data on fasting plasma glucose (FPG) and personal history of diabetes were used to estimate the prevalence of diabetes. Data on demographic characteristics, lifestyle risk factors, and lipid profiles were collected to identify risks factors using the multivariate logistic regression model. Results: In urban areas, the age- and gender-standardized prevalence of diabetes was 8.21%, and the age- and gender-standardized prevalence of diabetes was higher in the Uyghur population (10.47%) than in the Han population (7.36%). In rural areas, the age- and gender-standardized prevalence of diabetes was 6.08%, and it did not differ significantly between the Uyghur population (5.71%) and the Han population (6.59%). The results of the multivariate logistic regression analysis showed that older age, obesity, high triglycerides (TG), and hypertension were all associated with an increased risk of diabetes in the Uyghur and Han population. Urban residence and low high-density lipoprotein cholesterol (HDL-C) were associated with an increased risk of diabetes in the Uyghur population. Being an ex-drinker was associated with an increased risk of diabetes and heavy physical activity was associated with a decreased risk of diabetes in the Han population. Conclusions: Our study indicates that diabetes is more prevalent in the Uyghur population compared with the Han population in urban areas. Strategies aimed at the prevention of diabetes require ethnic targeting. PMID:26473908

  1. The association between ALS and population density: A population based study.

    PubMed

    Scott, Kirsten M; Abhinav, Kumar; Wijesekera, Lokesh; Ganesalingam, Jeban; Goldstein, Laura H; Janssen, Anna; Dougherty, Andrew; Willey, Emma; Stanton, Biba R; Turner, Martin R; Ampong, Mary-Ann; Sakel, Mohammed; Orrell, Richard; Howard, Robin; Shaw, Christopher E; Nigel Leigh, P; Al-Chalabi, Ammar

    2010-10-01

    We aimed to assess whether rural residence is associated with amyotrophic lateral sclerosis in the south-east of England using a population based register. Previous studies in different populations have produced contradictory findings. Residence defined by London borough or non-metropolitan district at time of diagnosis was recorded for each incident case in the South-East England ALS Register between 1995 and 2005. Each of the 26 boroughs or districts of the catchment area of the register was classified according to population density. Age- and sex-adjusted incidence of ALS was calculated for each region and the relationship with population density tested by linear regression, thereby controlling for the underlying population structure. We found that population density in region of residence at diagnosis explained 25% of the variance in ALS rates (r = 0.5, p < 0.01). Thus, in this cohort in the south-east of England, people with ALS were more likely to be resident in areas of high population density at diagnosis.

  2. The association between ALS and population density: A population based study

    PubMed Central

    SCOTT, KIRSTEN M.; ABHINAV, KUMAR; WIJESEKERA, LOKESH; GANESALINGAM, JEBAN; GOLDSTEIN, LAURA H.; JANSSEN, ANNA; DOUGHERTY, ANDREW; WILLEY, EMMA; STANTON, BIBA R.; TURNER, MARTIN R.; AMPONG, MARY-ANN; SAKEL, MOHAMMED; ORRELL, RICHARD; HOWARD, ROBIN; SHAW, CHRISTOPHER E.; LEIGH, P. NIGEL; AL-CHALABI, AMMAR

    2011-01-01

    We aimed to assess whether rural residence is associated with amyotrophic lateral sclerosis in the south-east of England using a population based register. Previous studies in different populations have produced contradictory findings. Residence defined by London borough or non-metropolitan district at time of diagnosis was recorded for each incident case in the South-East England ALS Register between 1995 and 2005. Each of the 26 boroughs or districts of the catchment area of the register was classified according to population density. Age- and sex-adjusted incidence of ALS was calculated for each region and the relationship with population density tested by linear regression, thereby controlling for the underlying population structure. We found that population density in region of residence at diagnosis explained 25% of the variance in ALS rates (r = 0.5, p < 0.01). Thus, in this cohort in the south-east of England, people with ALS were more likely to be resident in areas of high population density at diagnosis. PMID:20429684

  3. Genome-wide association of anthropometric traits in African- and African-derived populations

    PubMed Central

    Kang, Sun J.; Chiang, Charleston W.K.; Palmer, Cameron D.; Tayo, Bamidele O.; Lettre, Guillaume; Butler, Johannah L.; Hackett, Rachel; Adeyemo, Adebowale A.; Guiducci, Candace; Berzins, Ilze; Nguyen, Thutrang T.; Feng, Tao; Luke, Amy; Shriner, Daniel; Ardlie, Kristin; Rotimi, Charles; Wilks, Rainford; Forrester, Terrence; McKenzie, Colin A.; Lyon, Helen N.; Cooper, Richard S.; Zhu, Xiaofeng; Hirschhorn, Joel N.

    2010-01-01

    Genome-wide association (GWA) studies have identified common variants that are associated with a variety of traits and diseases, but most studies have been performed in European-derived populations. Here, we describe the first genome-wide analyses of imputed genotype and copy number variants (CNVs) for anthropometric measures in African-derived populations: 1188 Nigerians from Igbo-Ora and Ibadan, Nigeria, and 743 African-Americans from Maywood, IL. To improve the reach of our study, we used imputation to estimate genotypes at ∼2.1 million single-nucleotide polymorphisms (SNPs) and also tested CNVs for association. No SNPs or common CNVs reached a genome-wide significance level for association with height or body mass index (BMI), and the best signals from a meta-analysis of the two cohorts did not replicate in ∼3700 African-Americans and Jamaicans. However, several loci previously confirmed in European populations showed evidence of replication in our GWA panel of African-derived populations, including variants near IHH and DLEU7 for height and MC4R for BMI. Analysis of global burden of rare CNVs suggested that lean individuals possess greater total burden of CNVs, but this finding was not supported in an independent European population. Our results suggest that there are not multiple loci with strong effects on anthropometric traits in African-derived populations and that sample sizes comparable to those needed in European GWA studies will be required to identify replicable associations. Meta-analysis of this data set with additional studies in African-ancestry populations will be helpful to improve power to detect novel associations. PMID:20400458

  4. Population Cancer Risks Associated with Coal Mining: A Systematic Review

    PubMed Central

    Jenkins, Wiley D.; Christian, W. Jay; Mueller, Georgia; Robbins, K. Thomas

    2013-01-01

    Background Coal is produced across 25 states and provides 42% of US energy. With production expected to increase 7.6% by 2035, proximate populations remain at risk of exposure to carcinogenic coal products such as silica dust and organic compounds. It is unclear if population exposure is associated with increased risk, or even which cancers have been studied in this regard. Methods We performed a systematic review of English-language manuscripts published since 1980 to determine if coal mining exposure was associated with increased cancer risk (incidence and mortality). Results Of 34 studies identified, 27 studied coal mining as an occupational exposure (coal miner cohort or as a retrospective risk factor) but only seven explored health effects in surrounding populations. Overall, risk assessments were reported for 20 cancer site categories, but their results and frequency varied considerably. Incidence and mortality risk assessments were: negative (no increase) for 12 sites; positive for 1 site; and discordant for 7 sites (e.g. lung, gastric). However, 10 sites had only a single study reporting incidence risk (4 sites had none), and 11 sites had only a single study reporting mortality risk (2 sites had none). The ecological study data were particularly meager, reporting assessments for only 9 sites. While mortality assessments were reported for each, 6 had only a single report and only 2 sites had reported incidence assessments. Conclusions The reported assessments are too meager, and at times contradictory, to make definitive conclusions about population cancer risk due to coal mining. However, the preponderance of this and other data support many of Hill’s criteria for causation. The paucity of data regarding population exposure and risk, the widespread geographical extent of coal mining activity, and the continuing importance of coal for US energy, warrant further studies of population exposure and risk. PMID:23977014

  5. Manifold Modeling for Brain Population Analysis

    PubMed Central

    Gerber, Samuel; Tasdizen, Tolga; Fletcher, P. Thomas; Joshi, Sarang; Whitaker, Ross

    2010-01-01

    This paper describes a method for building efficient representations of large sets of brain images. Our hypothesis is that the space spanned by a set of brain images can be captured, to a close approximation, by a low-dimensional, nonlinear manifold. This paper presents a method to learn such a low-dimensional manifold from a given data set. The manifold model is generative—brain images can be constructed from a relatively small set of parameters, and new brain images can be projected onto the manifold. This allows to quantify the geometric accuracy of the manifold approximation in terms of projection distance. The manifold coordinates induce a Euclidean coordinate system on the population data that can be used to perform statistical analysis of the population. We evaluate the proposed method on the OASIS and ADNI brain databases of head MR images in two ways. First, the geometric fit of the method is qualitatively and quantitatively evaluated. Second, the ability of the brain manifold model to explain clinical measures is analyzed by linear regression in the manifold coordinate space. The regression models show that the manifold model is a statistically significant descriptor of clinical parameters. PMID:20579930

  6. ROADTRIPS: case-control association testing with partially or completely unknown population and pedigree structure.

    PubMed

    Thornton, Timothy; McPeek, Mary Sara

    2010-02-12

    Genome-wide association studies are routinely conducted to identify genetic variants that influence complex disorders. It is well known that failure to properly account for population or pedigree structure can lead to spurious association as well as reduced power. We propose a method, ROADTRIPS, for case-control association testing in samples with partially or completely unknown population and pedigree structure. ROADTRIPS uses a covariance matrix estimated from genome-screen data to correct for unknown population and pedigree structure while maintaining high power by taking advantage of known pedigree information when it is available. ROADTRIPS can incorporate data on arbitrary combinations of related and unrelated individuals and is computationally feasible for the analysis of genetic studies with millions of markers. In simulations with related individuals and population structure, including admixture, we demonstrate that ROADTRIPS provides a substantial improvement over existing methods in terms of power and type 1 error. The ROADTRIPS method can be used across a variety of study designs, ranging from studies that have a combination of unrelated individuals and small pedigrees to studies of isolated founder populations with partially known or completely unknown pedigrees. We apply the method to analyze two data sets: a study of rheumatoid arthritis in small UK pedigrees, from Genetic Analysis Workshop 15, and data from the Collaborative Study of the Genetics of Alcoholism on alcohol dependence in a sample of moderate-size pedigrees of European descent, from Genetic Analysis Workshop 14. We detect genome-wide significant association, after Bonferroni correction, in both studies.

  7. SIRT1 gene, schizophrenia and bipolar disorder in the Japanese population: an association study.

    PubMed

    Kishi, T; Fukuo, Y; Kitajima, T; Okochi, T; Yamanouchi, Y; Kinoshita, Y; Kawashima, K; Inada, T; Kunugi, H; Kato, T; Yoshikawa, T; Ujike, H; Ozaki, N; Iwata, N

    2011-04-01

    Several lines of evidence suggest that alterations in circadian rhythms might be associated with the pathophysiology of psychiatric disorders such as schizophrenia and bipolar disorder (BP). A recent study reported that SIRT1 is a molecule that plays an important role in the circadian clock system. Therefore, to evaluate the association among the SIRT1 gene, schizophrenia and BP, we conducted a case-control study of Japanese population samples (1158 schizophrenia patients, 1008 BP patients and 2127 controls) with four tagging SNPs (rs12778366, rs2273773, rs4746720 and rs10997875) in the SIRT1 gene. Marker-trait association analysis was used to evaluate the allele and the genotype association with the χ(2) test, and haplotype association analysis was evaluated with a likelihood ratio test. We showed an association between rs4746720 in the SIRT1 gene and schizophrenia in the allele and the genotype analysis. However, the significance of these associations did not survive after Bonferroni's correction for multiple testing. On the other hand, the SIRT1 gene was associated with Japanese schizophrenia in a haplotype-wise analysis (global P(all markers) = 4.89 × 10(-15)). Also, four tagging SNPs in the SIRT1 gene were not associated with BP. In conclusion, the SIRT1 gene may play an important role in the pathophysiology of schizophrenia in the Japanese population.

  8. Characterization of population exposure to organochlorines: a cluster analysis application.

    PubMed

    Guimarães, Raphael Mendonça; Asmus, Carmen Ildes Rodrigues Fróes; Burdorf, Alex

    2013-06-01

    This study aimed to show the results from a cluster analysis application in the characterization of population exposure to organochlorines through variables related to time and exposure dose. Characteristics of 354 subjects in a population exposed to organochlorine pesticides residues related to time and exposure dose were subjected to cluster analysis to separate them into subgroups. We performed hierarchical cluster analysis. To evaluate the classification accuracy, compared to intra-group and inter-group variability by ANOVA for each dimension. The aggregation strategy was accomplished by the method of Ward. It was, for the creation of clusters, variables associated with exposure and routes of contamination. The information on the estimated intake doses of compound were used to weight the values of exposure time at each of the routes, so as to obtain values proxy exposure intensity. The results showed three clusters: cluster 1 (n = 45), characteristics of greatest exposure, the cluster 2 (n = 103), intermediate exposure, and cluster 3 (n = 206), less exposure. The bivariate analyzes performed with groups that are groups showed a statistically significant difference. This study demonstrated the applicability of cluster analysis to categorize populations exposed to organochlorines and also points to the relevance of typological studies that may contribute to a better classification of subjects exposed to chemical agents, which is typical of environmental epidemiology studies to a wider understanding of etiological, preventive and therapeutic contamination.

  9. Social deprivation and population density are not associated with small area risk of amyotrophic lateral sclerosis.

    PubMed

    Rooney, James P K; Tobin, Katy; Crampsie, Arlene; Vajda, Alice; Heverin, Mark; McLaughlin, Russell; Staines, Anthony; Hardiman, Orla

    2015-10-01

    Evidence of an association between areal ALS risk and population density has been previously reported. We aim to examine ALS spatial incidence in Ireland using small areas, to compare this analysis with our previous analysis of larger areas and to examine the associations between population density, social deprivation and ALS incidence. Residential area social deprivation has not been previously investigated as a risk factor for ALS. Using the Irish ALS register, we included all cases of ALS diagnosed in Ireland from 1995-2013. 2006 census data was used to calculate age and sex standardised expected cases per small area. Social deprivation was assessed using the pobalHP deprivation index. Bayesian smoothing was used to calculate small area relative risk for ALS, whilst cluster analysis was performed using SaTScan. The effects of population density and social deprivation were tested in two ways: (1) as covariates in the Bayesian spatial model; (2) via post-Bayesian regression. 1701 cases were included. Bayesian smoothed maps of relative risk at small area resolution matched closely to our previous analysis at a larger area resolution. Cluster analysis identified two areas of significant low risk. These areas did not correlate with population density or social deprivation indices. Two areas showing low frequency of ALS have been identified in the Republic of Ireland. These areas do not correlate with population density or residential area social deprivation, indicating that other reasons, such as genetic admixture may account for the observed findings. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Association between electronic cigarette use and changes in quit attempts, success of quit attempts, use of smoking cessation pharmacotherapy, and use of stop smoking services in England: time series analysis of population trends.

    PubMed

    Beard, Emma; West, Robert; Michie, Susan; Brown, Jamie

    2016-09-13

     To estimate how far changes in the prevalence of electronic cigarette (e-cigarette) use in England have been associated with changes in quit success, quit attempts, and use of licensed medication and behavioural support in quit attempts.  Time series analysis of population trends.  Participants came from the Smoking Toolkit Study, which involves repeated, cross sectional household surveys of individuals aged 16 years and older in England. Data were aggregated on about 1200 smokers quarterly between 2006 and 2015. Monitoring data were also used from the national behavioural support programme; during the study, 8 029 012 quit dates were set with this programme.  England.  Prevalence of e-cigarette use in current smokers and during a quit attempt were used to predict quit success. Prevalence of e-cigarette use in current smokers was used to predict rate of quit attempts. Percentage of quit attempts involving e-cigarette use was also used to predict quit attempts involving use of prescription treatments, nicotine replacement therapy (NRT) on prescription and bought over the counter, and use of behavioural support. Analyses involved adjustment for a range of potential confounders.  The success rate of quit attempts increased by 0.098% (95% confidence interval 0.064 to 0.132; P<0.001) and 0.058% (0.038 to 0.078; P<0.001) for every 1% increase in the prevalence of e-cigarette use by smokers and e-cigarette use during a recent quit attempt, respectively. There was no clear evidence for an association between e-cigarette use and rate of quit attempts (β 0.025; 95% confidence interval -0.035 to 0.085; P=0.41), use of NRT bought over the counter (β 0.006; -0.088 to 0.077; P=0.89), use of prescription treatment (β -0.070; -0.152 to 0.013; P=0.10), or use of behavioural support (β -0.013; -0.102 to 0.077; P=0.78). A negative association was found between e-cigarette use during a recent quit attempt and use of NRT obtained on prescription (β -0.098; -0.189 to -0

  11. Assessing population exposure for landslide risk analysis using dasymetric cartography

    NASA Astrophysics Data System (ADS)

    Garcia, Ricardo A. C.; Oliveira, Sérgio C.; Zêzere, José L.

    2016-12-01

    Assessing the number and locations of exposed people is a crucial step in landslide risk management and emergency planning. The available population statistical data frequently have insufficient detail for an accurate assessment of potentially exposed people to hazardous events, mainly when they occur at the local scale, such as with landslides. The present study aims to apply dasymetric cartography to improving population spatial resolution and to assess the potentially exposed population. An additional objective is to compare the results with those obtained with a more common approach that uses, as spatial units, basic census units, which are the best spatial data disaggregation and detailed information available for regional studies in Portugal. Considering the Portuguese census data and a layer of residential building footprint, which was used as ancillary information, the number of exposed inhabitants differs significantly according to the approach used. When the census unit approach is used, considering the three highest landslide susceptible classes, the number of exposed inhabitants is in general overestimated. Despite the associated uncertainties of a general cost-benefit analysis, the presented methodology seems to be a reliable approach for gaining a first approximation of a more detailed estimation of exposed people. The approach based on dasymetric cartography allows the spatial resolution of population over large areas to be increased and enables the use of detailed landslide susceptibility maps, which are valuable for improving the exposed population assessment.

  12. Neuropeptide Y gene polymorphisms are not associated with obesity in a South Indian population.

    PubMed

    Bhaskar, L V K S; Thangaraj, K; Pardhasaradhi, G; Kumar, K P; Singh, L; Rao, V R

    2010-08-01

    Neuropeptide Y (NPY) gene has been shown to have a critical role in the regulation of satiety, reproduction, central endocrine and cardiovascular systems. Among the primary functions associated with NPY are its acute effects on feeding behavior and energy expenditure. The aim of this study is to evaluate the relationship between obesity and NPY gene polymorphisms in a South Indian Population. Three polymorphisms in NPY gene (Leu7Pro, Ser50Ser and A7735G) were analyzed in 263 individuals of an endogamous Kota population. On the basis of body mass index (BMI), they were divided into two groups. Associations were tested using logistic regression and haplotype analyses and linkage disequilibrium (LD). There was no evidence of deviation from Hardy-Weinberg equilibrium. Logistic regression analysis did not reveal significant association with obesity and NPY single-nucleotide polymorphisms (SNPs) in the present study. All three SNPs were in weak LD with low r (2) values. Haplotype analysis also did not yield significant association between NPY gene and obesity (global P=0.756). Our study did not validate the association between previously implicated SNPs in NPY gene and obesity in an Indian population. Population-specific validation of putative associations has far reaching implications for the future personal genomics medicine applications.

  13. Population-specific association of genes for telomere-associated proteins with longevity in an Italian population.

    PubMed

    Crocco, Paolina; Barale, Roberto; Rose, Giuseppina; Rizzato, Cosmeri; Santoro, Aurelia; De Rango, Francesco; Carrai, Maura; Fogar, Paola; Monti, Daniela; Biondi, Fiammetta; Bucci, Laura; Ostan, Rita; Tallaro, Federica; Montesanto, Alberto; Zambon, Carlo-Federico; Franceschi, Claudio; Canzian, Federico; Passarino, Giuseppe; Campa, Daniele

    2015-06-01

    Leukocyte telomere length (LTL) has been observed to be hereditable and correlated with longevity. However, contrasting results have been reported in different populations on the value of LTL heritability and on how biology of telomeres influences longevity. We investigated whether the variability of genes correlated to telomere maintenance is associated with telomere length and affects longevity in a population from Southern Italy (20-106 years). For this purpose we analyzed thirty-one polymorphisms in eight telomerase-associated genes of which twelve in the genes coding for the core enzyme (TERT and TERC) and the remaining in genes coding for components of the telomerase complex (TERF1, TERF2, TERF2IP, TNKS, TNKS2 and TEP1). We did not observe (after correcting for multiple testing) statistically significant associations between SNPs and LTL, possibly suggesting a low genetic influence of the variability of these genes on LTL in the elderly. On the other hand, we found that the variability of genes encoding for TERF1 and TNKS2, not directly involved in LTL, but important for keeping the integrity of the structure, shows a significant association with longevity. This suggests that the maintenance of these chromosomal structures may be critically important for preventing, or delaying, senescence and aging. Such a correlation was not observed in a population from northern Italy that we used as an independent replication set. This discrepancy is in line with previous reports regarding both the population specificity of results on telomere biology and the differences of aging in northern and southern Italy.

  14. Single-strand conformational polymorphism analysis of a common single nucleotide variation in WRAP53 gene, rs2287499, and evaluating its association in relation to breast cancer risk and prognosis among Iranian-Azeri population.

    PubMed

    Sedaie Bonab, Aida; Pouladi, Nasser; Hosseinpourfeizi, Mohammad Ali; Ravanbakhsh Gavgani, Reyhaneh; Dehghan, Roghayeh; Azarfam, Parvin; Montazeri, Vahid; Fakhrjou, Ashraf

    2014-09-01

    The WRAP53 (WD40-encoding RNA antisense to p53) gene encodes an antisense RNA, essential for p53 stabilization and induction upon DNA damage. Single nucleotide polymorphisms (SNPs) in WRAP53 have been associated with risk of cancer, which strengthens the role of WRAP53 in the pathogenesis of human malignancies. In fact, WRAP53 has been considered as a candidate cancer susceptibility gene. Accordingly, we performed a study to examine the association of a frequent genetic variation in WRAP53, rs2287499 (C/G), with breast cancer risk and prognosis among Iranian-Azeri population. A case-control association study, including 206 cases and 203 controls from Iranian-Azeri population, was conducted. Genomic DNA was extracted from peripheral blood and tumor samples by salting-out method. SNP genotyping was carried out by polymerase chain reaction-based single-strand conformational polymorphism (PCR-SSCP) technique. The sequence variation of SSCP banding patterns was determined by sequencing. The collected data were analyzed through statistical package for the social sciences software, using Chi-square (χ (2)) or Fisher's exact tests, with a significance level of 0.05. No significant differences in the allele and genotype frequencies between cases and controls were detected. Similarly, no significant associations between genotypes and clinicopathological data were observed. Concisely, no significant overall associations between rs2287499 and breast cancer risk and prognosis were detected in the studied population. The rs2287499 SNP is not associated with breast cancer predisposition in Iranian-Azeri women; it also cannot be used as a molecular biomarker to predict breast cancer prognosis in Iranian-Azeri population.

  15. Identification of loci affecting teat number by genome-wide association studies on three pig populations

    PubMed Central

    Tang, Jianhong; Zhang, Zhiyan; Yang, Bin; Guo, Yuanmei; Ai, Huashui; Long, Yi; Su, Ying; Cui, Leilei; Zhou, Liyu; Wang, Xiaopeng; Zhang, Hui; Wang, Chengbin; Ren, Jun; Huang, Lusheng; Ding, Nengshui

    2017-01-01

    Objective Three genome-wide association studies (GWAS) and a meta-analysis of GWAS were conducted to explore the genetic mechanisms underlying variation in pig teat number. Methods We performed three GWAS and a meta-analysis for teat number on three pig populations, including a White Duroc×Erhualian F2 resource population (n = 1,743), a Chinese Erhualian pig population (n = 320) and a Chinese Sutai pig population (n = 383). Results We detected 24 single nucleotide polymorphisms (SNPs) that surpassed the genome-wide significant level on Sus Scrofa chromosomes (SSC) 1, 7, and 12 in the F2 resource population, corresponding to four loci for pig teat number. We highlighted vertnin (VRTN) and lysine demethylase 6B (KDM6B) as two interesting candidate genes at the loci on SSC7 and SSC12. No significant associated SNPs were identified in the meta-analysis of GWAS. Conclusion The results verified the complex genetic architecture of pig teat number. The causative variants for teat number may be different in the three populations PMID:27165028

  16. [APOE gene polymorphisms associated with Down syndrome in Colombian populations].

    PubMed

    Rengifo, Lucero; Gaviria, Duverney; Serrano, Herman

    2012-06-01

    Introduction.Gene APOEε4 allele polymorphisms have been examined in Down syndrome because of the relationship between (a) the E4 isoform and (b) the type of Alzheimer's dementia that appears in individuals with Down syndrome. This isoform is considered a risk factor for Alzheimer's disease development and has been associated with early death in Down syndrome. Objectives. The polymorphisms in the APOE gene were characterized for Down syndrome individuals and their parents, in order to detect associations between the APOE polymorphisms and Down syndrome. Materials and methods. APOE gene polymorphisms were detected by RFLP-PCR and analyzed in 134 young individuals with Down syndrome, 87 mothers and 54 fathers, residents of the departments of Quindío and Risaralda, Colombia. The controls were 525 healthy individuals. Results. The APOEε3 allele and ε3/ε3 genotype were most frequent in all the populations (83-90% and 70-78%). The allelic frequency of APOEε2 was very low and ε2/ε2 (3-7%) was absent in Down syndrome and their parents. The allele APOEε4 was more frequent (11% vs. 9%) in Down syndrome individuals than in the controls. Comparing the allelic and genotypic frequencies between the populations with Down syndrome and their parents with the controls using Pearson c2 test and Fisher's exact test odds ratio, no statistically significant differences were found. Conclusions. No statistically significant association was found between the polymorphisms of the APOE gene and Down syndrome. Sample size or ethnic influences may have affected these results. More studies are necessary with other Colombian populations to determine possible associations in other genes related to Alzheimer's disease.

  17. Gender- and Age-Associated Differences in Serum Metabolite Profiles among Japanese Populations.

    PubMed

    Saito, Kosuke; Maekawa, Keiko; Kinchen, Jason M; Tanaka, Rieko; Kumagai, Yuji; Saito, Yoshiro

    2016-01-01

    Serum metabolites can reflect the diffusion/export of biochemicals from various organs. They can serve as biomarkers related to diseases and therapeutic efficacy/toxicity. While studies in Caucasians suggested that subject gender and age can affect circulating metabolite profiles, the Japanese population has not been surveyed. Our objective was to delineate gender- and age-associated differences in serum metabolite profiles among Japanese populations. Using a mass spectrometry-based global metabolomics approach, 516 endogenous metabolites were detected in sera from Japanese individuals. The principal component analysis identified gender as the primary component, followed by age, suggesting that these two criteria were key contributors to variations in the dataset. Gender-associated differences were observed in 31 and 25% of metabolites in the young (age 25-35) and old (ages 55-65) populations, respectively, in redox homeostasis, and in steroid and purine nucleotide metabolism pathways. Age-associated differences were observed in 24 and 23% of metabolites in men and women, respectively. No pathway was commonly highlighted. Thus, gender and age impact on metabolite profiles in the Japanese population. Our results provide useful information to explore biomarkers for clinical applications in the Japanese population and to assess the applicability of known biomarkers identified in other populations to the Japanese population.

  18. Association study in three different populations between the GPR88 gene and major psychoses

    PubMed Central

    Del Zompo, Maria; Deleuze, Jean-François; Chillotti, Caterina; Cousin, Emmanuelle; Niehaus, Dana; Ebstein, Richard P; Ardau, Raffaella; Macé, Sandrine; Warnich, Louise; Mujahed, Mustafa; Severino, Giovanni; Dib, Colette; Jordaan, Esme; Murad, Ibrahim; Soubigou, Stéphane; Koen, Liezl; Bannoura, Issam; Rocher, Corinne; Laurent, Claudine; Derock, Murielle; Faucon Biguet, Nicole; Mallet, Jacques; Meloni, Rolando

    2014-01-01

    GPR88, coding for a G protein-coupled orphan receptor that is highly represented in the striatum, is a strong functional candidate gene for neuropsychiatric disorders and is located at 1p22-p21, a chromosomal region that we have previously linked to bipolar disorder (BD) in the Sardinian population. In order to ascertain the relevance of GPR88 as a risk factor for psychiatric diseases, we performed a genetic association analysis between GPR88 and BD in a sample of triads (patient and both parents) recruited in the Sardinian and the Palestinian population as well as between GPR88 and schizophrenia (SZ) in triads from the Xhosa population in South Africa. We found a positive association between GPR88 and BD in the Sardinian and Palestinian triads. Moreover, we found a positive association between GPR88 and SZ in triads from the Xhosa population in South Africa. When these results were corrected for multiple testing, the association between GPR88 and BD was maintained in the Palestinian population. Thus, these results suggest that GPR88 deserves consideration as a candidate gene for psychiatric diseases and requires to be further investigated in other populations. PMID:24689078

  19. Transcription analysis of neonicotinoid resistance in Mediterranean (MED) populations of B. tabaci reveal novel cytochrome P450s, but no nAChR mutations associated with the phenotype.

    PubMed

    Ilias, Aris; Lagnel, Jacques; Kapantaidaki, Despoina E; Roditakis, Emmanouil; Tsigenopoulos, Costas S; Vontas, John; Tsagkarakou, Anastasia

    2015-11-14

    Bemisia tabaci is one of the most damaging agricultural pests world-wide. Although its control is based on insecticides, B. tabaci has developed resistance against almost all classes of insecticides, including neonicotinoids. We employed an RNA-seq approach to generate genome wide expression data and identify genes associated with neonicotinoid resistance in Mediterranean (MED) B. tabaci (Q1 biotype). Twelve libraries from insecticide resistant and susceptible whitefly populations were sequenced on an Illumina Next-generation sequencing platform, and genomic sequence information of approximately 73 Gbp was generated. A reference transcriptome was built by de novo assembly and functionally annotated. A total of 146 P450s, 18 GSTs and 23 CCEs enzymes (unigenes) potentially involved in the detoxification of xenobiotics were identified, along with 78 contigs encoding putative target proteins of six different insecticide classes. Ten unigenes encoding nicotinic Acetylcholine Receptors (nAChR), the target of neoinicotinoids, were identified and phylogenetically classified. No nAChR polymorphism potentially related with the resistant phenotypes, was observed among the studied strains. DE analysis revealed that among the 550 differentially (logFC > 1) over-transcribed unigenes, 52 detoxification enzymes were over expressed including unigenes with orthologues in P450s, GSTs, CCE and UDP-glucuronosyltransferases. Eight P450 unigenes belonging to clades CYP2, CYP3 and CYP4 were highly up-regulated (logFC > 2) including CYP6CM1, a gene already known to confer imidacloprid resistance in B. tabaci. Using quantitative qPCRs, a larger screening of field MED B. tabaci from Crete with known neonicotinoid phenotype was performed to associate expression levels of P450s with resistance levels. Expression levels of five P450s, including CYP6CM1, were found associated with neonicotinoid resistance. However, a significant correlation was found only in CYP303 and CYP6CX3, with imidacloprid

  20. Association Pattern of Interleukin-1 Receptor-Associated Kinase-4 Gene Polymorphisms with Allergic Rhinitis in a Han Chinese Population

    PubMed Central

    Zhang, Yuan; Lin, Xiaoping; Desrosiers, Martin; Zhang, Wei; Meng, Na; Zhao, Liping

    2011-01-01

    Objective Interleukin-1 receptor-associated kinase-4 (IRAK-4) encodes a kinase that is essential for NF-kB activation in Toll-like receptor and T-cell receptor signaling pathways, indicating a possible crosstalk between innate and acquired immunities. We attempted to determine whether the polymorphisms in the Interleukin-1 receptor-associated kinase-4 (IRAK-4) gene are associated with allergic rhinitis (AR) in the Han Chinese population. Methods A population of 379 patients with AR and 333 healthy controls was studied. Blood was drawn for DNA extraction and total serum immunoglobulin E (IgE). A total of 11 single nucleotide polymorphisms (SNPs) in IRAK-4 were selected and individually genotyped. Results Significant allelic differences between cases and controls were obtained for the SNP of rs3794262 in the IRAK-4 gene. In the stratified analysis for gender, two SNPs (rs4251431 and rs6582484) in males appeared as significant associations. Subgroup analysis for the presence of different allergen sensitivities displayed associations only in the house dust mite-allergic cohorts (rs3794262, rs4251481). None of the selected SNPs in IRAK-4 was associated with total IgE level. The haplotype analyisis indicated GCCTGCGA was significantly associated with AR. The SNP-SNP interaction information analysis indicated that the selected sets of polymorphisms had no synergistic effect. Conclusions Our findings did not support the potential contribution of the IRAK-4 gene to serum IgE levels. However, the results demonstrated a gender- and allergen-dependant association pattern between polymorphisms in IRAK-4 and AR in Chinese population. PMID:21738793

  1. Microsatellite analysis of genetic diversity and population structure of Arabian horse populations.

    PubMed

    Khanshour, Anas; Conant, Eleanore; Juras, Rytis; Cothran, Ernest Gus

    2013-01-01

    The Arabian horse ignites imagination throughout the world. Populations of this breed exist in many countries, and recent genetic work has examined the diversity and ancestry of a few of these populations in isolation. Here, we explore 7 different populations of Arabians represented by 682 horses. Three of these are Middle Eastern populations from near the historical origin of the breed, including Syrian, Persian, and Saudi Arabian. The remaining Western populations are found in Europe (the Shagya Arabian and Polish Arabian) and in America (American Arabian). Analysis of genetic structure was carried out using 15 microsatellite loci. Genetic distances, analysis of molecular variance, factorial correspondence analysis, and a Bayesian method were applied. The results consistently show higher level of diversity within the Middle Eastern populations than the Western populations. The Western Arabian populations were the main source among population variation. Genetic differentiation was not strong among all Middle Eastern populations, but all American Arabians showed differentiation from Middle Eastern populations and were somewhat uniform among themselves. Here, we explore the diversities of many different populations of Arabian horses and find that populations not from the Middle East have noticeably lower levels of diversity, which may adversely affect the health of these populations.

  2. Breast cancer and microbial cancer incidence in female populations around the world: a surprising hyperbolic association.

    PubMed

    Savu, Anamaria; Potter, John; Li, Suwen; Yasui, Yutaka

    2008-09-01

    Current literature on cancer epidemiology typically discusses etiology of cancer by cancer type. Risks of different cancer types are, however, correlated at population level and may provide etiological clues. We showed previously an unexpected very high positive correlation between breast cancer (BC) and young-adult Hodgkin disease incidence rates. In a population-based case-control study of BC, older ages at the first Epstein-Barr virus exposure, indicated by older ages at onset of infectious mononucleosis, were associated with elevated BC risk. Here we examine BC risk in association with microbial cancer (MC) risk in female populations across the world. MC cancers are cervical, liver and stomach cancers with established causal associations with human papillomaviruses, hepatitis viruses, and helicobacter pylori, respectively. We examined age-adjusted BC and MC incidence rates in 74 female populations around the world with cancer registries. Our analysis suggests that BC and MC rates are inversely associated in a special mathematical form such that the product of BC rate and MC rate is approximately constant across world female populations. A differential equation model with solutions consistent to the observed inverse association was derived. BC and MC rates were modeled as functions of an exposure level to unspecified common factors that influence the 2 rates. In conjunction with previously reported evidence, we submit a hypothesis that BC etiology may have an appreciable link with microbial exposures (and/or immunological responses to them), the lack of which, especially in early life, may elevate BC risk.

  3. Automated analysis of a diverse synapse population.

    PubMed

    Busse, Brad; Smith, Stephen

    2013-01-01

    Synapses of the mammalian central nervous system are highly diverse in function and molecular composition. Synapse diversity per se may be critical to brain function, since memory and homeostatic mechanisms are thought to be rooted primarily in activity-dependent plastic changes in specific subsets of individual synapses. Unfortunately, the measurement of synapse diversity has been restricted by the limitations of methods capable of measuring synapse properties at the level of individual synapses. Array tomography is a new high-resolution, high-throughput proteomic imaging method that has the potential to advance the measurement of unit-level synapse diversity across large and diverse synapse populations. Here we present an automated feature extraction and classification algorithm designed to quantify synapses from high-dimensional array tomographic data too voluminous for manual analysis. We demonstrate the use of this method to quantify laminar distributions of synapses in mouse somatosensory cortex and validate the classification process by detecting the presence of known but uncommon proteomic profiles. Such classification and quantification will be highly useful in identifying specific subpopulations of synapses exhibiting plasticity in response to perturbations from the environment or the sensory periphery.

  4. Automated Analysis of a Diverse Synapse Population

    PubMed Central

    Busse, Brad; Smith, Stephen

    2013-01-01

    Synapses of the mammalian central nervous system are highly diverse in function and molecular composition. Synapse diversity per se may be critical to brain function, since memory and homeostatic mechanisms are thought to be rooted primarily in activity-dependent plastic changes in specific subsets of individual synapses. Unfortunately, the measurement of synapse diversity has been restricted by the limitations of methods capable of measuring synapse properties at the level of individual synapses. Array tomography is a new high-resolution, high-throughput proteomic imaging method that has the potential to advance the measurement of unit-level synapse diversity across large and diverse synapse populations. Here we present an automated feature extraction and classification algorithm designed to quantify synapses from high-dimensional array tomographic data too voluminous for manual analysis. We demonstrate the use of this method to quantify laminar distributions of synapses in mouse somatosensory cortex and validate the classification process by detecting the presence of known but uncommon proteomic profiles. Such classification and quantification will be highly useful in identifying specific subpopulations of synapses exhibiting plasticity in response to perturbations from the environment or the sensory periphery. PMID:23555213

  5. Association of the adiponectin gene variations with risk of ischemic stroke in a Korean population.

    PubMed

    Cheong, My-Young; Bang, Ok-Sun; Cha, Min-Ho; Park, Young-Kyu; Kim, Seung-Ho; Kim, Young Joo

    2011-01-01

    Stroke is the second leading cause of death and a major cause of morbidity and mortality worldwide. Evidence of variations in adiponectin (AdipoQ) genes that are associated with ischemic stroke has not been consistent, and it is unclear whether the same loci contribute to these associations in the Korean population. Using a Korean population, we tested ischemic stroke-associated AdipoQ markers. In a preliminary genome-wide association study using 320 250 k Affymetrix NSP chips, AdipoQ was found to be associated with ischemic stroke in Koreans. To study of AdipoQ, a further 673 ischemic stroke patients and 267 unrelated individuals without a history of stroke or transient ischemic attack were examined in a case-control study. Six polymorphisms (rs182052G > A, rs16861205G > A, rs822391T > C, rs822396A > G, rs12495941G > T and rs3774261A > G) that had a minor allele frequency of over 1% were strongly associated with stroke (p < 0.05). Two of these, rs822391T > C and rs822396A > G showed this association on both dominant and additive logistic regression analysis after adjusting for age and sex. The haplotypes ht 1 (AGGCGG and AAGTAG) were significantly associated with susceptibility to stroke. Our findings show that polymorphisms in AdipoQ are associated with risk for ischemic stroke in the Korean population. This study lends further support to the putative role of AdipoQ in stroke.

  6. Bayesian analysis of genetic differentiation between populations.

    PubMed Central

    Corander, Jukka; Waldmann, Patrik; Sillanpää, Mikko J

    2003-01-01

    We introduce a Bayesian method for estimating hidden population substructure using multilocus molecular markers and geographical information provided by the sampling design. The joint posterior distribution of the substructure and allele frequencies of the respective populations is available in an analytical form when the number of populations is small, whereas an approximation based on a Markov chain Monte Carlo simulation approach can be obtained for a moderate or large number of populations. Using the joint posterior distribution, posteriors can also be derived for any evolutionary population parameters, such as the traditional fixation indices. A major advantage compared to most earlier methods is that the number of populations is treated here as an unknown parameter. What is traditionally considered as two genetically distinct populations, either recently founded or connected by considerable gene flow, is here considered as one panmictic population with a certain probability based on marker data and prior information. Analyses of previously published data on the Moroccan argan tree (Argania spinosa) and of simulated data sets suggest that our method is capable of estimating a population substructure, while not artificially enforcing a substructure when it does not exist. The software (BAPS) used for the computations is freely available from http://www.rni.helsinki.fi/~mjs. PMID:12586722

  7. Bayesian analysis of genetic differentiation between populations.

    PubMed

    Corander, Jukka; Waldmann, Patrik; Sillanpää, Mikko J

    2003-01-01

    We introduce a Bayesian method for estimating hidden population substructure using multilocus molecular markers and geographical information provided by the sampling design. The joint posterior distribution of the substructure and allele frequencies of the respective populations is available in an analytical form when the number of populations is small, whereas an approximation based on a Markov chain Monte Carlo simulation approach can be obtained for a moderate or large number of populations. Using the joint posterior distribution, posteriors can also be derived for any evolutionary population parameters, such as the traditional fixation indices. A major advantage compared to most earlier methods is that the number of populations is treated here as an unknown parameter. What is traditionally considered as two genetically distinct populations, either recently founded or connected by considerable gene flow, is here considered as one panmictic population with a certain probability based on marker data and prior information. Analyses of previously published data on the Moroccan argan tree (Argania spinosa) and of simulated data sets suggest that our method is capable of estimating a population substructure, while not artificially enforcing a substructure when it does not exist. The software (BAPS) used for the computations is freely available from http://www.rni.helsinki.fi/~mjs.

  8. Association analysis of food allergens.

    PubMed

    Kanagawa, Yoshiyuki; Matsumoto, Shinya; Koike, Soichi; Imamura, Tomoaki

    2009-06-01

    Food allergy patients are known to present with allergic reactions to multiple allergens, but extrapolating these associations is difficult. Data mining, a procedure that analyzes characteristic combinations among large amounts of information, is often used to analyze and predict consumer purchasing behaviour. We applied this technique to the extrapolation of food allergen associations in allergy patients. We sent 1510 families our 'Questionnaire survey for the prevention of food allergies'. Responses noting 6549 allergens came from 878 families with 1383 patients, including 402 with anaphylaxis. Some results of the survey have already been published and here we presented the results of our association analysis of combinations of food allergens. Egg, milk, wheat, peanuts, and buckwheat are the most common food allergens. The most common simultaneous combinations of these allergens were 'egg-milk', 'egg-wheat', and 'milk-wheat'. The occurrence probability of a combination (i.e. one person suffering from a certain allergen also suffers from another) is called 'confidence'. Confidence was higher for 'chicken-egg', 'abalone-salmon eggs', and 'matsutake mushroom-milk'. As well, the combinations of 'crab-shrimp', 'squid-shrimp', and 'squid-crab' also indicated higher values in a statistical examination of the occurrence probabilities of these allergen combinations (Z-score). From the results of the association analysis, we speculated that some food allergens, such as abalone, orange, salmon, chicken, pork, matsutake mushroom, peach and apple did not independently induce food allergies. We also found that combinations, such as 'crab-shrimp', 'squid-shrimp', 'squid-crab', 'chicken-beef', and 'salmon-mackerel' had strong associations.

  9. [Obesity and leptin association in three Chilean aboriginal populations].

    PubMed

    Pérez, F; Santos, J L; Albala, C; Calvillán, M; Carrasco, E

    2000-01-01

    Although there is a clear relationship between body mass index and leptin levels, few authors have addressed the possible influence of ethnic factors on these levels. To measure serum leptin in three different Chilean aboriginal populations. Fasting serum leptin and insulin levels were measured by radioimmunoassay in 345 rural mapuche individuals, 247 rural aymara subjects and 162 urban mapuche subjects. A body mass index of 27.5 kg/m2 was used as cutoff point to classify study subjects. Among the three ethnic groups, women had serum leptin levels three times higher than men. In all three ethnic groups, there was a significant association between leptin levels, body mass index and gender (r2 = 0.32 and 0.5 p < 0.001, in rural mapuche, r2 = 0.32 and 0.5 p < 0.001, in aymara and r2 = 0.24 and 0.49, p < 0.001 in urban mapuche populations). No differences in leptin levels were observed for the interaction between age and insulin. The increments per quartile in leptin levels were lower among mapuche than aymara individuals. Rural mapuche individuals have a high frequency of obesity. However their leptin levels are lower than those of aymara or urban mapuche populations. The higher leptin levels observed in urban mapuche subjects could be due to environmental influences.

  10. GST polymorphisms are associated with hepatocellular carcinoma risk in Chinese population

    PubMed Central

    Yu, Lei; Wang, Chun-Yu; Xi, Bo; Sun, Lei; Wang, Ruo-Qi; Yan, Yin-Kun; Zhu, Li-Ying

    2011-01-01

    AIM: To investigate the association between GSTM1 and GSTT1 polymorphisms and the risk of hepatocellular carcinoma (HCC) in Chinese population. METHODS: Literature databases including PubMed, ISI web of science and other databases were searched. Pooled odds ratio (OR) and 95% CI were calculated using random- or fixed- effects model. Subgroup analysis and sensitivity analysis were also performed. RESULTS: Nineteen studies of GSTM1 (2660 cases and 4017 controls) and 16 studies of GSTT1 (2410 cases and 3669 controls) were included. The GSTM1/GSTT1 null genotypes were associated with increased risk of HCC in Chinese population (for GSTM1, OR = 1.487, 95% CI: 1.159 to 1.908, P = 0.002; for GSTT1, OR = 1.510, 95% CI: 1.236 to 1.845, P = 0.000). No publication bias was detected. In subgroup analysis, glutathione S-transferases polymorphisms were significantly associated with HCC risk among the subjects living in high-incidence areas, but not among the subjects living in low-incidence areas. CONCLUSION: The present meta-analysis suggests that GSTM1/GSTT1 null genotypes are associated with increased risk of HCC in Chinese population. PMID:21912475

  11. Fine-scale patterns of population stratification confound rare variant association tests.

    PubMed

    O'Connor, Timothy D; Kiezun, Adam; Bamshad, Michael; Rich, Stephen S; Smith, Joshua D; Turner, Emily; Leal, Suzanne M; Akey, Joshua M

    2013-01-01

    Advances in next-generation sequencing technology have enabled systematic exploration of the contribution of rare variation to Mendelian and complex diseases. Although it is well known that population stratification can generate spurious associations with common alleles, its impact on rare variant association methods remains poorly understood. Here, we performed exhaustive coalescent simulations with demographic parameters calibrated from exome sequence data to evaluate the performance of nine rare variant association methods in the presence of fine-scale population structure. We find that all methods have an inflated spurious association rate for parameter values that are consistent with levels of differentiation typical of European populations. For example, at a nominal significance level of 5%, some test statistics have a spurious association rate as high as 40%. Finally, we empirically assess the impact of population stratification in a large data set of 4,298 European American exomes. Our results have important implications for the design, analysis, and interpretation of rare variant genome-wide association studies.

  12. In silico genotyping of the maize nested association mapping population

    PubMed Central

    Guo, Baohong

    2010-01-01

    Nested Association Mapping (NAM) has been proposed as a means to combine the power of linkage mapping with the resolution of association mapping. It is enabled through sequencing or array genotyping of parental inbred lines while using low-cost, low-density genotyping technologies for their segregating progenies. For purposes of data analyses of NAM populations, parental genotypes at a large number of Single Nucleotide Polymorphic (SNP) loci need to be projected to their segregating progeny. Herein we demonstrate how approximately 0.5 million SNPs that have been genotyped in 26 parental lines of the publicly available maize NAM population can be projected onto their segregating progeny using only 1,106 SNP loci that have been genotyped in both the parents and their 5,000 progeny. The challenge is to estimate both the genotype and genetic location of the parental SNP genotypes in segregating progeny. Both challenges were met by estimating their expected genotypic values conditional on observed flanking markers through the use of both physical and linkage maps. About 90%, of 500,000 genotyped SNPs from the maize HapMap project, were assigned linkage map positions using linear interpolation between the maize Accessioned Gold Path (AGP) and NAM linkage maps. Of these, almost 70% provided high probability estimates of genotypes in almost 5,000 recombinant inbred lines. PMID:21289856

  13. Population ecology of Aspergillus flavus associated with Mississippi Delta soils.

    PubMed

    Zablotowicz, R M; Abbas, H K; Locke, M A

    2007-10-01

    Understanding the source of Aspergillus flavus is required to manage aflatoxin contamination of maize (Zea mays L.). Studies assessed A. flavus propagules, Fusarium spp., and total fungi associated with Mississippi Delta soils. Soils from 12 and 15 sites were collected in 2000 and 2001, respectively. The propagule density of A. flavus ranged from log(10) 2.0 to 4.3 colony-forming units (cfu) g(-1) soil, while total fusaria ranged from log(10) 3.0 to 5.4 cfu g(-1) soil. The highest populations of A. flavus were associated with soils containing higher organic matter, especially in sites under a no-tillage management. The frequency of aflatoxin production in isolates ranged from 13 to 81% depending on soil. In 2001, there was a highly significant correlation between A. flavus and the history of maize cultivation. Soil fertility factors such as organic matter content, nitrate and extractable phosphorus correlated with the density of Aspergillus, Fusarium spp., and total fungi. The relationship between soil parameters and Aspergillus populations may be useful in predicting the contribution of soil microflora to aflatoxin contamination.

  14. Microbial Population of Feedlot Waste and Associated Sites

    PubMed Central

    Rhodes, R. A.; Hrubant, G. R.

    1972-01-01

    A quantitative determination was made every 2 months for a year of the microflora of beef cattle waste and runoff at a medium-sized midwestern feedlot. Counts were obtained for selected groups of organisms in waste taken from paved areas of pens cleaned daily and, therefore, reflect the flora of raw waste. Overall, in terms of viable count per gram dry weight, the feedlot waste contained 1010 total organisms, 109 anaerobes, 108 gram-negative bacteria, 107 coliforms, 106 sporeformers, and 105 yeasts, fungi, and streptomycetes. The specific numbers and pattern of these groups of organisms varied only slightly during the study in spite of a wide variation in weather. Data indicate that little microbial growth occurs in the waste as it exists in the feedlot. Runoff from the pens contained the same general population pattern but with greater variation attributable to volume of liquid. Comparable determinations of an associated field disposal area (before and after cropping), stockpiled waste, and elevated dirt areas in the pens indicate that fungi, and especially streptomycetes, are the aerobic organisms most associated with final stabilization of the waste. Yeasts, which are the dominant type of organism in the ensiled corn fed the cattle, do not occur in large numbers in the animal waste. Large ditches receiving runoff and subsurface water from the fields have a population similar to the runoff but with fewer coliforms. PMID:16349931

  15. Genetic diversity and population structure of a diverse set of rice germplasm for association mapping.

    PubMed

    Jin, Liang; Lu, Yan; Xiao, Peng; Sun, Mei; Corke, Harold; Bao, Jinsong

    2010-08-01

    Germplasm diversity i