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Sample records for association scan meta-analysis

  1. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.

    PubMed

    Fan, Qiao; Verhoeven, Virginie J M; Wojciechowski, Robert; Barathi, Veluchamy A; Hysi, Pirro G; Guggenheim, Jeremy A; Höhn, René; Vitart, Veronique; Khawaja, Anthony P; Yamashiro, Kenji; Hosseini, S Mohsen; Lehtimäki, Terho; Lu, Yi; Haller, Toomas; Xie, Jing; Delcourt, Cécile; Pirastu, Mario; Wedenoja, Juho; Gharahkhani, Puya; Venturini, Cristina; Miyake, Masahiro; Hewitt, Alex W; Guo, Xiaobo; Mazur, Johanna; Huffman, Jenifer E; Williams, Katie M; Polasek, Ozren; Campbell, Harry; Rudan, Igor; Vatavuk, Zoran; Wilson, James F; Joshi, Peter K; McMahon, George; St Pourcain, Beate; Evans, David M; Simpson, Claire L; Schwantes-An, Tae-Hwi; Igo, Robert P; Mirshahi, Alireza; Cougnard-Gregoire, Audrey; Bellenguez, Céline; Blettner, Maria; Raitakari, Olli; Kähönen, Mika; Seppala, Ilkka; Zeller, Tanja; Meitinger, Thomas; Ried, Janina S; Gieger, Christian; Portas, Laura; van Leeuwen, Elisabeth M; Amin, Najaf; Uitterlinden, André G; Rivadeneira, Fernando; Hofman, Albert; Vingerling, Johannes R; Wang, Ya Xing; Wang, Xu; Tai-Hui Boh, Eileen; Ikram, M Kamran; Sabanayagam, Charumathi; Gupta, Preeti; Tan, Vincent; Zhou, Lei; Ho, Candice E H; Lim, Wan'e; Beuerman, Roger W; Siantar, Rosalynn; Tai, E-Shyong; Vithana, Eranga; Mihailov, Evelin; Khor, Chiea-Chuen; Hayward, Caroline; Luben, Robert N; Foster, Paul J; Klein, Barbara E K; Klein, Ronald; Wong, Hoi-Suen; Mitchell, Paul; Metspalu, Andres; Aung, Tin; Young, Terri L; He, Mingguang; Pärssinen, Olavi; van Duijn, Cornelia M; Jin Wang, Jie; Williams, Cathy; Jonas, Jost B; Teo, Yik-Ying; Mackey, David A; Oexle, Konrad; Yoshimura, Nagahisa; Paterson, Andrew D; Pfeiffer, Norbert; Wong, Tien-Yin; Baird, Paul N; Stambolian, Dwight; Wilson, Joan E Bailey; Cheng, Ching-Yu; Hammond, Christopher J; Klaver, Caroline C W; Saw, Seang-Mei; Rahi, Jugnoo S; Korobelnik, Jean-François; Kemp, John P; Timpson, Nicholas J; Smith, George Davey; Craig, Jamie E; Burdon, Kathryn P; Fogarty, Rhys D; Iyengar, Sudha K; Chew, Emily; Janmahasatian, Sarayut; Martin, Nicholas G; MacGregor, Stuart; Xu, Liang; Schache, Maria; Nangia, Vinay; Panda-Jonas, Songhomitra; Wright, Alan F; Fondran, Jeremy R; Lass, Jonathan H; Feng, Sheng; Zhao, Jing Hua; Khaw, Kay-Tee; Wareham, Nick J; Rantanen, Taina; Kaprio, Jaakko; Pang, Chi Pui; Chen, Li Jia; Tam, Pancy O; Jhanji, Vishal; Young, Alvin L; Döring, Angela; Raffel, Leslie J; Cotch, Mary-Frances; Li, Xiaohui; Yip, Shea Ping; Yap, Maurice K H; Biino, Ginevra; Vaccargiu, Simona; Fossarello, Maurizio; Fleck, Brian; Yazar, Seyhan; Tideman, Jan Willem L; Tedja, Milly; Deangelis, Margaret M; Morrison, Margaux; Farrer, Lindsay; Zhou, Xiangtian; Chen, Wei; Mizuki, Nobuhisa; Meguro, Akira; Mäkelä, Kari Matti

    2016-01-01

    Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia. PMID:27020472

  2. Meta-analysis of gene–environment-wide association scans accounting for education level identifies additional loci for refractive error

    PubMed Central

    Fan, Qiao; Verhoeven, Virginie J. M.; Wojciechowski, Robert; Barathi, Veluchamy A.; Hysi, Pirro G.; Guggenheim, Jeremy A.; Höhn, René; Vitart, Veronique; Khawaja, Anthony P.; Yamashiro, Kenji; Hosseini, S Mohsen; Lehtimäki, Terho; Lu, Yi; Haller, Toomas; Xie, Jing; Delcourt, Cécile; Pirastu, Mario; Wedenoja, Juho; Gharahkhani, Puya; Venturini, Cristina; Miyake, Masahiro; Hewitt, Alex W.; Guo, Xiaobo; Mazur, Johanna; Huffman, Jenifer E.; Williams, Katie M.; Polasek, Ozren; Campbell, Harry; Rudan, Igor; Vatavuk, Zoran; Wilson, James F.; Joshi, Peter K.; McMahon, George; St Pourcain, Beate; Evans, David M.; Simpson, Claire L.; Schwantes-An, Tae-Hwi; Igo, Robert P.; Mirshahi, Alireza; Cougnard-Gregoire, Audrey; Bellenguez, Céline; Blettner, Maria; Raitakari, Olli; Kähönen, Mika; Seppala, Ilkka; Zeller, Tanja; Meitinger, Thomas; Ried, Janina S.; Gieger, Christian; Portas, Laura; van Leeuwen, Elisabeth M.; Amin, Najaf; Uitterlinden, André G.; Rivadeneira, Fernando; Hofman, Albert; Vingerling, Johannes R.; Wang, Ya Xing; Wang, Xu; Tai-Hui Boh, Eileen; Ikram, M. Kamran; Sabanayagam, Charumathi; Gupta, Preeti; Tan, Vincent; Zhou, Lei; Ho, Candice E. H.; Lim, Wan'e; Beuerman, Roger W.; Siantar, Rosalynn; Tai, E-Shyong; Vithana, Eranga; Mihailov, Evelin; Khor, Chiea-Chuen; Hayward, Caroline; Luben, Robert N.; Foster, Paul J.; Klein, Barbara E. K.; Klein, Ronald; Wong, Hoi-Suen; Mitchell, Paul; Metspalu, Andres; Aung, Tin; Young, Terri L.; He, Mingguang; Pärssinen, Olavi; van Duijn, Cornelia M.; Jin Wang, Jie; Williams, Cathy; Jonas, Jost B.; Teo, Yik-Ying; Mackey, David A.; Oexle, Konrad; Yoshimura, Nagahisa; Paterson, Andrew D.; Pfeiffer, Norbert; Wong, Tien-Yin; Baird, Paul N.; Stambolian, Dwight; Wilson, Joan E. Bailey; Cheng, Ching-Yu; Hammond, Christopher J.; Klaver, Caroline C. W.; Saw, Seang-Mei; Rahi, Jugnoo S.; Korobelnik, Jean-François; Kemp, John P.; Timpson, Nicholas J.; Smith, George Davey; Craig, Jamie E.; Burdon, Kathryn P.; Fogarty, Rhys D.; Iyengar, Sudha K.; Chew, Emily; Janmahasatian, Sarayut; Martin, Nicholas G.; MacGregor, Stuart; Xu, Liang; Schache, Maria; Nangia, Vinay; Panda-Jonas, Songhomitra; Wright, Alan F.; Fondran, Jeremy R.; Lass, Jonathan H.; Feng, Sheng; Zhao, Jing Hua; Khaw, Kay-Tee; Wareham, Nick J.; Rantanen, Taina; Kaprio, Jaakko; Pang, Chi Pui; Chen, Li Jia; Tam, Pancy O.; Jhanji, Vishal; Young, Alvin L.; Döring, Angela; Raffel, Leslie J.; Cotch, Mary-Frances; Li, Xiaohui; Yip, Shea Ping; Yap, Maurice K.H.; Biino, Ginevra; Vaccargiu, Simona; Fossarello, Maurizio; Fleck, Brian; Yazar, Seyhan; Tideman, Jan Willem L.; Tedja, Milly; Deangelis, Margaret M.; Morrison, Margaux; Farrer, Lindsay; Zhou, Xiangtian; Chen, Wei; Mizuki, Nobuhisa; Meguro, Akira; Mäkelä, Kari Matti

    2016-01-01

    Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10−5), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia. PMID:27020472

  3. A Meta-Analysis of Genome-Wide Association Scans Identifies IL18RAP, PTPN2, TAGAP, and PUS10 As Shared Risk Loci for Crohn's Disease and Celiac Disease

    PubMed Central

    Boucher, Gabrielle; Beauchamp, Claudine; Trynka, Gosia; Dubois, Patrick C.; Lagacé, Caroline; Stokkers, Pieter C. F.; Hommes, Daan W.; Barisani, Donatella; Palmieri, Orazio; Annese, Vito; van Heel, David A.; Weersma, Rinse K.; Daly, Mark J.; Wijmenga, Cisca; Rioux, John D.

    2011-01-01

    Crohn's disease (CD) and celiac disease (CelD) are chronic intestinal inflammatory diseases, involving genetic and environmental factors in their pathogenesis. The two diseases can co-occur within families, and studies suggest that CelD patients have a higher risk to develop CD than the general population. These observations suggest that CD and CelD may share common genetic risk loci. Two such shared loci, IL18RAP and PTPN2, have already been identified independently in these two diseases. The aim of our study was to explicitly identify shared risk loci for these diseases by combining results from genome-wide association study (GWAS) datasets of CD and CelD. Specifically, GWAS results from CelD (768 cases, 1,422 controls) and CD (3,230 cases, 4,829 controls) were combined in a meta-analysis. Nine independent regions had nominal association p-value <1.0×10−5 in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value <1×10−2 in CelD and <1×10−3 in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37×10−8 and 6.39×10−9, respectively, in the meta-analysis. The other seven had not been reported as shared loci and thus were tested in additional CelD (3,149 cases and 4,714 controls) and CD (1,835 cases and 1,669 controls) cohorts. Two of these loci, TAGAP and PUS10, showed significant evidence of replication (Bonferroni corrected p-values <0.0071) in the combined CelD and CD replication cohorts and were firmly established as shared risk loci of genome-wide significance, with overall combined p-values of 1.55×10−10 and 1.38×10−11 respectively. Through a meta-analysis of GWAS data from CD and CelD, we have identified four shared risk loci: PTPN2, IL18RAP, TAGAP, and PUS10. The combined analysis of the two datasets provided the power, lacking in the individual GWAS for single diseases, to detect shared loci with a relatively small effect. PMID:21298027

  4. General Framework for Meta-Analysis of Haplotype Association Tests.

    PubMed

    Wang, Shuai; Zhao, Jing Hua; An, Ping; Guo, Xiuqing; Jensen, Richard A; Marten, Jonathan; Huffman, Jennifer E; Meidtner, Karina; Boeing, Heiner; Campbell, Archie; Rice, Kenneth M; Scott, Robert A; Yao, Jie; Schulze, Matthias B; Wareham, Nicholas J; Borecki, Ingrid B; Province, Michael A; Rotter, Jerome I; Hayward, Caroline; Goodarzi, Mark O; Meigs, James B; Dupuis, Josée

    2016-04-01

    For complex traits, most associated single nucleotide variants (SNV) discovered to date have a small effect, and detection of association is only possible with large sample sizes. Because of patient confidentiality concerns, it is often not possible to pool genetic data from multiple cohorts, and meta-analysis has emerged as the method of choice to combine results from multiple studies. Many meta-analysis methods are available for single SNV analyses. As new approaches allow the capture of low frequency and rare genetic variation, it is of interest to jointly consider multiple variants to improve power. However, for the analysis of haplotypes formed by multiple SNVs, meta-analysis remains a challenge, because different haplotypes may be observed across studies. We propose a two-stage meta-analysis approach to combine haplotype analysis results. In the first stage, each cohort estimate haplotype effect sizes in a regression framework, accounting for relatedness among observations if appropriate. For the second stage, we use a multivariate generalized least square meta-analysis approach to combine haplotype effect estimates from multiple cohorts. Haplotype-specific association tests and a global test of independence between haplotypes and traits are obtained within our framework. We demonstrate through simulation studies that we control the type-I error rate, and our approach is more powerful than inverse variance weighted meta-analysis of single SNV analysis when haplotype effects are present. We replicate a published haplotype association between fasting glucose-associated locus (G6PC2) and fasting glucose in seven studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and we provide more precise haplotype effect estimates. PMID:27027517

  5. Meta-analysis of genome-wide linkage scans for renal function traits

    PubMed Central

    Rao, Madhumathi; Mottl, Amy K.; Cole, Shelley A.; Umans, Jason G.; Freedman, Barry I.; Bowden, Donald W.; Langefeld, Carl D.; Fox, Caroline S.; Yang, Qiong; Cupples, Adrienne; Iyengar, Sudha K.; Hunt, Steven C.

    2012-01-01

    Background. Several genome scans have explored the linkage of chronic kidney disease phenotypes to chromosomic regions with disparate results. Genome scan meta-analysis (GSMA) is a quantitative method to synthesize linkage results from independent studies and assess their concordance. Methods. We searched PubMed to identify genome linkage analyses of renal function traits in humans, such as estimated glomerular filtration rate (GFR), albuminuria, serum creatinine concentration and creatinine clearance. We contacted authors for numerical data and extracted information from individual studies. We applied the GSMA nonparametric approach to combine results across 14 linkage studies for GFR, 11 linkage studies for albumin creatinine ratio, 11 linkage studies for serum creatinine and 4 linkage studies for creatinine clearance. Results. No chromosomal region reached genome-wide statistical significance in the main analysis which included all scans under each phenotype; however, regions on Chromosomes 7, 10 and 16 reached suggestive significance for linkage to two or more phenotypes. Subgroup analyses by disease status or ethnicity did not yield additional information. Conclusions. While heterogeneity across populations, methodologies and study designs likely explain this lack of agreement, it is possible that linkage scan methodologies lack the resolution for investigating complex traits. Combining family-based linkage studies with genome-wide association studies may be a powerful approach to detect private mutations contributing to complex renal phenotypes. PMID:21622988

  6. Association Between Psoriasis and Subclinical Atherosclerosis: A Meta-Analysis.

    PubMed

    Fang, Na; Jiang, Menglin; Fan, Yu

    2016-05-01

    The association between psoriasis and carotid intima-media thickness (CIMT) or impaired flow-mediated dilation (FMD) remains controversial. We aimed to evaluate the extent of subclinical atherosclerosis as measured by CIMT and FMD in patients with psoriasis by conducting a meta-analysis.A systematic literature search was performed using PubMed, Embase, Cochrane databases, China National Knowledge Infrastructure, and VIP databases up to February 2015. Observational studies investigating CIMT or FMD in patients with psoriasis and controls were eligible. Psoriatic patients and controls were at least age- and sex-matched. Random-effects analysis was used to estimate the weighted mean difference (WMD) and 95% confidence interval (CI) between psoriatic patients and controls.A total of 20 studies were identified and analyzed. Meta-analysis showed that psoriatic patients had a significantly thicker CIMT (WMD 0.11 mm; 95% CI 0.08-0.15) and lower FMD (WMD -2.79%; -4.14% to -1.43%) than those in controls. Subgroup analysis indicated that psoriatic arthritis appeared to have less impaired FMD (WMD -2.45%) and thinner CIMT (WMD 0.10 mm). Psoriatic patients with mean age >45 years had much thicker CIMT (WMD 0.13 mm). The impaired FMD (WMD -3.99%) seemed more pronounced in psoriatic patients with mean age <45 years.This meta-analysis suggests that patients with psoriasis are associated with excessive risk of subclinical atherosclerosis. Screening and monitoring CIMT and brachial artery FMD may be recommended to identify a subgroup of psoriatic patients at higher risk for cardiovascular events. PMID:27196459

  7. Association between Arsenic Exposure and Diabetes: A Meta-Analysis

    PubMed Central

    Sung, Tzu-Ching; Huang, Jhih-Wei; Guo, How-Ran

    2015-01-01

    Studies on the association between arsenic exposure and diabetes mellitus (DM) yielded inconsistent results. Epidemiologic data on the associations between arsenic exposures via inhalation and DM are limited. Therefore, we conducted a meta-analysis to evaluate the risk of DM associated with arsenic exposure. We searched the related literature through a systematic approach and analyzed the data according to the exposure route (inhalation and ingestion). We used random-effect models to estimate the summary relative risks (RRs) for DM associated with arsenic exposure and used I2 statistics to assess the heterogeneity of studies. We identified 38 relevant studies, of which the 32 on the ingestion route showed a significant association between arsenic exposure and DM (RR = 1.57; 95% CI 1.27–1.93). Focusing on the 24 studies in which the diagnosis of DM was confirmed using laboratory tests or medical records, we found that the summary RR was 1.71 (95% CI 1.32–2.23), very close to the overall estimates. We concluded that ingested arsenic is associated with the development of DM, but the heterogeneity among the studies may affect the results. PMID:26000288

  8. Genome-Wide Association Study to Identify Common Variants Associated with Brachial Circumference: A Meta-Analysis of 14 Cohorts

    PubMed Central

    Boraska, Vesna; Day-Williams, Aaron; Franklin, Christopher S.; Elliott, Katherine S.; Panoutsopoulou, Kalliope; Tachmazidou, Ioanna; Albrecht, Eva; Bandinelli, Stefania; Beilin, Lawrence J.; Bochud, Murielle; Cadby, Gemma; Ernst, Florian; Evans, David M.; Hayward, Caroline; Hicks, Andrew A.; Huffman, Jennifer; Huth, Cornelia; James, Alan L.; Klopp, Norman; Kolcic, Ivana; Kutalik, Zoltán; Lawlor, Debbie A.; Musk, Arthur W.; Pehlic, Marina; Pennell, Craig E.; Perry, John R. B.; Peters, Annette; Polasek, Ozren; Pourcain, Beate St; Ring, Susan M.; Salvi, Erika; Schipf, Sabine; Staessen, Jan A.; Teumer, Alexander; Timpson, Nicholas; Vitart, Veronique; Warrington, Nicole M.; Yaghootkar, Hanieh; Zemunik, Tatijana; Zgaga, Lina; An, Ping; Anttila, Verneri; Borecki, Ingrid B.; Holmen, Jostein; Ntalla, Ioanna; Palotie, Aarno; Pietiläinen, Kirsi H.; Wedenoja, Juho; Winsvold, Bendik S.; Dedoussis, George V.; Kaprio, Jaakko; Province, Michael A.; Zwart, John-Anker; Burnier, Michel; Campbell, Harry; Cusi, Daniele; Davey Smith, George; Frayling, Timothy M.; Gieger, Christian; Palmer, Lyle J.; Pramstaller, Peter P.; Rudan, Igor; Völzke, Henry; Wichmann, H. -Erich; Wright, Alan F.; Zeggini, Eleftheria

    2012-01-01

    Brachial circumference (BC), also known as upper arm or mid arm circumference, can be used as an indicator of muscle mass and fat tissue, which are distributed differently in men and women. Analysis of anthropometric measures of peripheral fat distribution such as BC could help in understanding the complex pathophysiology behind overweight and obesity. The purpose of this study is to identify genetic variants associated with BC through a large-scale genome-wide association scan (GWAS) meta-analysis. We used fixed-effects meta-analysis to synthesise summary results across 14 GWAS discovery and 4 replication cohorts comprising overall 22,376 individuals (12,031 women and 10,345 men) of European ancestry. Individual analyses were carried out for men, women, and combined across sexes using linear regression and an additive genetic model: adjusted for age and adjusted for age and BMI. We prioritised signals for follow-up in two-stages. We did not detect any signals reaching genome-wide significance. The FTO rs9939609 SNP showed nominal evidence for association (p<0.05) in the age-adjusted strata for men and across both sexes. In this first GWAS meta-analysis for BC to date, we have not identified any genome-wide significant signals and do not observe robust association of previously established obesity loci with BC. Large-scale collaborations will be necessary to achieve higher power to detect loci underlying BC. PMID:22479309

  9. Meta-analysis of genome-wide association studies of attention deficit/hyperactivity disorder

    PubMed Central

    Neale, Benjamin M; Medland, Sarah E.; Ripke, Stephan; Asherson, Philip; Franke, Barbara; Lesch, Klaus-Peter; Faraone, Stephen V.; Nguyen, Thuy Trang; Schäfer, Helmut; Holmans, Peter; Daly, Mark; Steinhausen, Hans-Christoph; Freitag, Christine; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Walitza, Susanne; Warnke, Andreas; Meyer, Jobst; Palmason, Haukur; Buitelaar, Jan; Vasquez, Alejandro Arias; Lambregts-Rommelse, Nanda; Gill, Michael; Anney, Richard J.L.; Langely, Kate; O’Donovan, Michael; Williams, Nigel; Owen, Michael; Thapar, Anita; Kent, Lindsey; Sergeant, Joseph; Roeyers, Herbert; Mick, Eric; Biederman, Joseph; Doyle, Alysa; Smalley, Susan; Loo, Sandra; Hakonarson, Hakon; Elia, Josephine; Todorov, Alexandre; Miranda, Ana; Mulas, Fernando; Ebstein, Richard P.; Rothenberger, Aribert; Banaschewski, Tobias; Oades, Robert D.; Sonuga-Barke, Edmund; McGough, James; Nisenbaum, Laura; Middleton, Frank; Hu, Xiaolan; Nelson, Stan

    2010-01-01

    Objective Although twin and family studies have shown Attention Deficit/Hyperactivity Disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association scans (GWAS) have not yielded significant results, we conducted a meta-analysis of existing studies to boost statistical power. Method We used data from four projects: a) the Children’s Hospital of Philadelphia (CHOP), b) phase I of the International Multicenter ADHD Genetics project (IMAGE), c) phase II of IMAGE (IMAGE II), and d) the Pfizer funded study from the University of California, Los Angeles, Washington University and the Massachusetts General Hospital (PUWMa). The final sample size consisted of 2,064 trios, 896 cases and 2,455 controls. For each study, we imputed HapMap SNPs, computed association test statistics and transformed them to Z-scores, and then combined weighted Z-scores in a meta-analysis. Results No genome-wide significant associations were found, although an analysis of candidate genes suggests they may be involved in the disorder. Conclusions Given that ADHD is a highly heritable disorder, our negative results suggest that the effects of common ADHD risk variants must, individually, be very small or that other types of variants, e.g. rare ones, account for much of the disorder’s heritability. PMID:20732625

  10. A systematic review and meta-analysis of the association between eating disorders and bone density.

    PubMed

    Robinson, L; Aldridge, V; Clark, E M; Misra, M; Micali, N

    2016-06-01

    This meta-analysis investigates the effect of an eating disorder on bone mineral density in two eating disorder subtypes. Following conflicting findings in previous literature, this study finds that not only anorexia nervosa, but also bulimia nervosa has a detrimental effect on BMD. Key predictors of this relationship are discussed. This systematic review and meta-analysis investigates bone mineral density (BMD) in individuals with anorexia nervosa (AN) and bulimia nervosa (BN) in comparison to healthy controls (HCs). AN has been associated with low BMD and a risk of fractures and mixed results have been obtained for the relationship between BN and BMD. Deciphering the effect these two ED subtypes on BMD will determine the effect of low body weight (a characteristic of AN) versus the effects of periods of restrictive eating and malnutrition which are common to both AN and BN. We conducted a systematic search through the electronic databases MedLine, EMBASE and PsychInfo and the Cochrane Library to investigate and quantify this relationship. We screened 544 articles and included 27 studies in a random-effect meta-analysis and calculated the standardised mean difference (SMD) in BMD between women with a current diagnosis of AN (n = 785) vs HCs (n = 979) and a current diagnosis of BN (n = 187) vs HCs (n = 350). The outcome measures investigated were spinal, hip, femoral neck and whole body BMD measured by DXA or DPA scanning. A meta-regression investigated the effect of factors including age, duration since diagnosis, duration of amenorrhea and BMI on BMD. The mean BMI of participants was 16.65 kg/m(2) (AN), 21.16 kg/m(2) (BN) and 22.06 kg/m(2) (HC). Spine BMD was lowest in AN subjects (SMD, -3.681; 95 % CI, -4.738, -2.625; p < 0.0001), but also lower in BN subjects compared with HCs (SMD, -0.472; 95 % CI, -0.688, -0.255; p < 0.0001). Hip, whole body and femoral neck BMD were reduced to a statistically significant level in AN but not BN

  11. Meta-analysis for Discovering Rare-Variant Associations: Statistical Methods and Software Programs

    PubMed Central

    Tang, Zheng-Zheng; Lin, Dan-Yu

    2015-01-01

    There is heightened interest in using next-generation sequencing technologies to identify rare variants that influence complex human diseases and traits. Meta-analysis is essential to this endeavor because large sample sizes are required for detecting associations with rare variants. In this article, we provide a comprehensive overview of statistical methods for meta-analysis of sequencing studies for discovering rare-variant associations. Specifically, we discuss the calculation of relevant summary statistics from participating studies, the construction of gene-level association tests, the choice of transformation for quantitative traits, the use of fixed-effects versus random-effects models, and the removal of shadow association signals through conditional analysis. We also show that meta-analysis based on properly calculated summary statistics is as powerful as joint analysis of individual-participant data. In addition, we demonstrate the performance of different meta-analysis methods by using both simulated and empirical data. We then compare four major software packages for meta-analysis of rare-variant associations—MASS, RAREMETAL, MetaSKAT, and seqMeta—in terms of the underlying statistical methodology, analysis pipeline, and software interface. Finally, we present PreMeta, a software interface that integrates the four meta-analysis packages and allows a consortium to combine otherwise incompatible summary statistics. PMID:26094574

  12. Association between cadmium exposure and renal cancer risk: a meta-analysis of observational studies

    PubMed Central

    Song, Ju kun; Luo, Hong; Yin, Xin hai; Huang, Guang lei; Luo, Si yang; Lin, Du ren; Yuan, Dong Bo; Zhang, Wei; Zhu, Jian guo

    2015-01-01

    Cadmium (Cd) is a widespread environmental pollutant and has been a recognized carcinogen for several decades. Many observational studies reported Cd exposure might be one cause of renal cancer. However, these findings are inconsistent. We conducted a meta-analysis to evaluate the relationship between cadmium exposure and renal cancer risk. A comprehensive PubMed and Embase search was conducted to retrieve observational studies meeting our meta-analysis criteria. A combined odds ratio (OR) and corresponding 95% confidence interval (CI) were applied to assess the association between Cd exposure and renal cancer risk. The meta-analysis showed that a high Cd exposure significantly increased renal cancer 1.47 times (OR = 1.47; 95% CI = 1.27 to 1.71, for highest versus lowest category of cadmium categories). The significant association remained consistent when stratified by geographic region and gender, however mixed results were produced when stratified by sample size, study design, NOS score, adjustment for covariates, effects measure, and exposure type. Our results indicated that a high Cd exposure was associated with increased renal cancer risk and the association was higher for occupational exposure compared with non-occupational exposure. This meta-analysis suggests that a high Cd exposure may be a risk factor for renal cancer in occupational population. PMID:26656678

  13. Meta-analysis genomewide association of pork quality traits: ultimate pH and shear force

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is common practice to perform genome-wide association analysis (GWA) using a genomic evaluation model of a single population. Joint analysis of several populations is more difficult. An alternative to joint analysis could be the meta-analysis (MA) of several GWA from independent genomic evaluatio...

  14. Methods for meta-analysis of genome-wide association studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A limitation of many genome-wide association studies (GWA) in animal breeding is that there are many loci with small effect sizes; thus, larger sample sizes (N) are required to guarantee suitable power of detection. For increasing N, results from different GWA can be combined in a meta-analysis (MA-...

  15. Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Neale, Benjamin M.; Medland, Sarah E.; Ripke, Stephan; Asherson, Philip; Franke, Barbara; Lesch, Klaus-Peter; Faraone, Stephen V.; Nguyen, Thuy Trang; Schafer, Helmut; Holmans, Peter; Daly, Mark; Steinhausen, Hans-Christoph; Freitag, Christine; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Walitza, Susanne; Warnke, Andreas; Meyer, Jobst; Palmason, Haukur; Buitelaar, Jan; Vasquez, Alejandro Arias; Lambregts-Rommelse, Nanda; Gill, Michael; Anney, Richard J. L.; Langely, Kate; O'Donovan, Michael; Williams, Nigel; Owen, Michael; Thapar, Anita; Kent, Lindsey; Sergeant, Joseph; Roeyers, Herbert; Mick, Eric; Biederman, Joseph; Doyle, Alysa; Smalley, Susan; Loo, Sandra; Hakonarson, Hakon; Elia, Josephine; Todorov, Alexandre; Miranda, Ana; Mulas, Fernando; Ebstein, Richard P.; Rothenberger, Aribert; Banaschewski, Tobias; Oades, Robert D.; Sonuga-Barke, Edmund; McGough, James; Nisenbaum, Laura; Middleton, Frank; Hu, Xiaolan; Nelson, Stan

    2010-01-01

    Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of…

  16. Association between tea and coffee consumption and risk of laryngeal cancer: a meta-analysis

    PubMed Central

    Ouyang, Zhiguo; Wang, Zhaoyan; Jin, Jian

    2014-01-01

    Objective: Epidemiological studies evaluating the association of tea and coffee consumption and the risk of laryngeal cancer have produced inconsistent results. Thus, we conducted a meta-analysis to assess the relationship between tea and coffee consumption and laryngeal cancer risk. Methods: Pertinent studies were identified by a search in PubMed, Web of Knowledge and Wan Fang Med Online. The random effect model was used based on heterogeneity test. Publication bias was estimated using Egger’s regression asymmetry test. As a result, 11 articles were included in this meta-analysis. Results: For tea consumption and laryngeal cancer, data from 8 studies including 2167 laryngeal cancer cases were used, and the pooled results suggested that highest tea consumption versus lowest level wasn’t associated with the risk of laryngeal cancer [summary RR = 0.909, 95% CI = 0.674-1.227]. Eight studies comprising 2596 laryngeal cancer cases for coffee consumption and laryngeal cancer risk were included, and no association was found (summary RR = 1.218, 95% CI = 0.915-1.622). Conclusions: Finding from this meta-analysis suggested that tea and coffee consumption weren’t associated with the risk of laryngeal cancer. Since the potential biases and confounders could not be ruled out completely in this meta-analysis, further studies are warranted to confirm this result. PMID:25664021

  17. Association between increase in fixed penalties and road safety outcomes: A meta-analysis.

    PubMed

    Elvik, Rune

    2016-07-01

    Studies that have evaluated the association between increases in traffic fine amounts (fixed penalties) and changes in compliance with road traffic law or the number of accidents are synthesised by means of meta-analysis. The studies were few and different in many respects. Nine studies were included in the meta-analysis of changes in compliance. Four studies were included in the meta-analysis of changes in accidents. Increasing traffic fines was found to be associated with small changes in the rate of violations. The changes were non-linear. For increases up to about 100%, violations were reduced. For larger increases, no reduction in violations was found. A small reduction in fatal accidents was associated with increased fixed penalties, varying between studies from less than 1-12%. The main pattern of changes in violations was similar in the fixed-effects and random-effects models of meta-analysis, meta-regression and when simple (non-weighted) mean values were computed. The main findings are thus robust, although most of the primary studies did not control very well for potentially confounding factors. Summary estimates of changes in violations or accidents should be treated as provisional and do not necessarily reflect causal relationships. PMID:27085146

  18. Association of Serum Uric Acid Levels in Psoriasis: A Systematic Review and Meta-Analysis.

    PubMed

    Li, Xin; Miao, Xiao; Wang, Hongshen; Wang, Yifei; Li, Fulun; Yang, Qiong; Cui, Rutao; Li, Bin

    2016-05-01

    High levels of serum uric acid (SUAC) are frequently detected in patients with psoriasis. However, the relationship between psoriasis and hyperuricemia remains unknown. Here we conducted a meta-analysis to identify the SUAC levels in subjects with psoriasis and to determine whether there is an associated risk between psoriasis and hyperuricemia.A comprehensive search of the literature from January 1980 to November 2014 across 7 databases (MEDLINE, Embase, Cochrane Central Register, and 4 Chinese databases) was conducted to determine whether there is an associated risk between psoriasis and hyperuricemia.Among the 170 identified reports, 14 observational studies were included in this meta-analysis. We found a significant higher SUAC level (MD 0.68, 95% CI 0.26-1.09; P = 0.002) in patients with psoriasis in Western Europe, but no significant differences were found between the East Asia and India subgroup (MD 1.22, 95% CI -0.13-2.56; P = 0.08) or the Middle East subgroup (MD 0.48, 95% CI -0.49-1.44; P = 0.33). Similar results were obtained from the meta-analysis of SUAC levels in subjects with severe psoriasis.Our meta-analysis showed that the correlation between psoriasis and hyperuricemia was either ethnicity- or region-dependent and that patients with psoriasis in Western Europe were more likely to have hyperuricemia. PMID:27175702

  19. METASEQ: PRIVACY PRESERVING META-ANALYSIS OF SEQUENCING-BASED ASSOCIATION STUDIES*

    PubMed Central

    SINGH, ANGAD PAL; ZAFER, SAMREEN; PE’ER, ITSIK

    2013-01-01

    Human genetics recently transitioned from GWAS to studies based on NGS data. For GWAS, small effects dictated large sample sizes, typically made possible through meta-analysis by exchanging summary statistics across consortia. NGS studies groupwise-test for association of multiple potentially-causal alleles along each gene. They are subject to similar power constraints and therefore likely to resort to meta-analysis as well. The problem arises when considering privacy of the genetic information during the data-exchange process. Many scoring schemes for NGS association rely on the frequency of each variant thus requiring the exchange of identity of the sequenced variant. As such variants are often rare, potentially revealing the identity of their carriers and jeopardizing privacy. We have thus developed MetaSeq, a protocol for meta-analysis of genome-wide sequencing data by multiple collaborating parties, scoring association for rare variants pooled per gene across all parties. We tackle the challenge of tallying frequency counts of rare, sequenced alleles, for meta-analysis of sequencing data without disclosing the allele identity and counts, thereby protecting sample identity. This apparent paradoxical exchange of information is achieved through cryptographic means. The key idea is that parties encrypt identity of genes and variants. When they transfer information about frequency counts in cases and controls, the exchanged data does not convey the identity of a mutation and therefore does not expose carrier identity. The exchange relies on a 3rd party, trusted to follow the protocol although not trusted to learn about the raw data. We show applicability of this method to publicly available exome-sequencing data from multiple studies, simulating phenotypic information for powerful meta-analysis. The MetaSeq software is publicly available as open source. PMID:23424140

  20. Association between NSAIDs and Clostridium difficile-Associated Diarrhea: A Systematic Review and Meta-Analysis

    PubMed Central

    Permpalung, Nitipong; Upala, Sikarin; Sanguankeo, Anawin; Sornprom, Suthanya

    2016-01-01

    Objective. Clostridium difficile infection is a leading cause of nosocomial diarrhea in developed countries. Studies evaluating the associations of increased risk of community-acquired CDAD and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) have yielded inconclusive results. We conducted a systematic review and meta-analysis to compare the odds of NSAID exposure in patients with CDAD versus patients without CDAD in both community-based and healthcare-associated settings. Methods. Relevant observational studies indexed in PubMed/MEDLINE and EMBASE up to February 2015 were analyzed and data were extracted from nine studies. Of these, eight studies were included in the meta-analysis. Results. A search of the databases resulted in 987 articles. The nine studies from which data were extracted involved over 39,000 subjects. The pooled odds ratio for history of NSAID use in participants with CDAD compared with controls was 1.41 (95% CI 1.06–1.87; p < 0.01), indicating a significant increased odds of CDAD among patients exposed to NSAIDs. Conclusions. To the best of our knowledge, this is the first study of its nature to demonstrate the association between the use of NSAIDs and increased risk of CDAD. Further studies to evaluate if any specific types of NSAIDs can increase the risk of CDAD are warranted.

  1. Genetics of serum BDNF: Meta-analysis of the Val66Met and genome-wide association study

    PubMed Central

    Terracciano, Antonio; Piras, Maria Grazia; Lobina, Monia; Mulas, Antonella; Meirelles, Osorio; Sutin, Angelina R.; Chan, Wayne; Sanna, Serena; Uda, Manuela; Crisponi, Laura; Schlessinger, David

    2011-01-01

    Objectives Lower levels of serum Brain Derived Neurotrophic Factor (BDNF) is one of the best known biomarkers of depression. To identify genetic variants associated with serum BDNF, we tested the Val66Met (rs6265) functional variant and conducted a genome-wide association scan (GWAS). Methods In a community-based sample (N = 2054; aged 19 to 101, M = 51, SD = 15) from Sardinia, Italy, we measured serum BDNF concentration and conducted a GWAS. Results We estimated the heritability of serum BDNF to be 0.48 from sib-pairs. There was no association between serum BDNF and Val66Met in the SardiNIA sample and in a meta-analysis of published studies (k = 13 studies, total n = 4727, p = 0.92). Although no genome-wide significant associations were identified, some evidence of association was found in the BDNF gene (rs11030102, P = .001) and at two loci (rs7170215, P = 4.8×10−5 and rs11073742 P = 1.2×10−5) near and within NTRK3 gene, a neurotrophic tyrosine kinase receptor. Conclusions Our study and meta-analysis of the literature indicate that the BDNF Val66Met variant is not associated with serum BDNF, but other variants in the BDNF and NTRK3 genes might regulate the level of serum BDNF. PMID:22047184

  2. Refining genome-wide linkage intervals using a meta-analysis of genome-wide association studies identifies loci influencing personality dimensions.

    PubMed

    Amin, Najaf; Hottenga, Jouke-Jan; Hansell, Narelle K; Janssens, A Cecile J W; de Moor, Marleen H M; Madden, Pamela A F; Zorkoltseva, Irina V; Penninx, Brenda W; Terracciano, Antonio; Uda, Manuela; Tanaka, Toshiko; Esko, Tonu; Realo, Anu; Ferrucci, Luigi; Luciano, Michelle; Davies, Gail; Metspalu, Andres; Abecasis, Goncalo R; Deary, Ian J; Raikkonen, Katri; Bierut, Laura J; Costa, Paul T; Saviouk, Viatcheslav; Zhu, Gu; Kirichenko, Anatoly V; Isaacs, Aaron; Aulchenko, Yurii S; Willemsen, Gonneke; Heath, Andrew C; Pergadia, Michele L; Medland, Sarah E; Axenovich, Tatiana I; de Geus, Eco; Montgomery, Grant W; Wright, Margaret J; Oostra, Ben A; Martin, Nicholas G; Boomsma, Dorret I; van Duijn, Cornelia M

    2013-08-01

    Personality traits are complex phenotypes related to psychosomatic health. Individually, various gene finding methods have not achieved much success in finding genetic variants associated with personality traits. We performed a meta-analysis of four genome-wide linkage scans (N=6149 subjects) of five basic personality traits assessed with the NEO Five-Factor Inventory. We compared the significant regions from the meta-analysis of linkage scans with the results of a meta-analysis of genome-wide association studies (GWAS) (N∼17 000). We found significant evidence of linkage of neuroticism to chromosome 3p14 (rs1490265, LOD=4.67) and to chromosome 19q13 (rs628604, LOD=3.55); of extraversion to 14q32 (ATGG002, LOD=3.3); and of agreeableness to 3p25 (rs709160, LOD=3.67) and to two adjacent regions on chromosome 15, including 15q13 (rs970408, LOD=4.07) and 15q14 (rs1055356, LOD=3.52) in the individual scans. In the meta-analysis, we found strong evidence of linkage of extraversion to 4q34, 9q34, 10q24 and 11q22, openness to 2p25, 3q26, 9p21, 11q24, 15q26 and 19q13 and agreeableness to 4q34 and 19p13. Significant evidence of association in the GWAS was detected between openness and rs677035 at 11q24 (P-value=2.6 × 10(-06), KCNJ1). The findings of our linkage meta-analysis and those of the GWAS suggest that 11q24 is a susceptible locus for openness, with KCNJ1 as the possible candidate gene. PMID:23211697

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

    PubMed Central

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

    2016-01-01

    Objectives The association between body mass index (BMI) and hot flash risk has not been specifically clarifies yet. This meta-analysis was, therefore, conducted to estimate the association between overweight and obesity and hot flash risk. Methods We searched PubMed, Web of Science, and Scopus for observational studies addressing the association between BMI and hot flash until August 2015. Data were independently extracted and analyzed using 95% odds ratio (OR), and confidence intervals (CI) based on the random-effects models. Results We identified 2,244 references and conducted seven studies with 4,219 participants. The association between hot flash and overweight was estimated 1.13 (95% CI: 0.97-1.32) and that of obesity was estimated 1.79 (95% CI: 1.52-2.11). No evidence of heterogeneity and publication bias was observed. Conclusion This meta-analysis demonstrated that, though not to a great extent, obesity does increase the risk of hot flash. The findings from this meta-analysis indicated that obesity is associated with an increased risk of hot flash. Further large prospective cohort studies are required to provide convincing evidence as to whether or not BMI is associated with an increased risk of hot flashes. PMID:27152309

  4. Association of OPN rs11730582 polymorphism with cancer risk: a meta-analysis

    PubMed Central

    He, Lanlan; Wang, Yong

    2016-01-01

    Purpose Several molecular epidemiological studies have investigated the association between OPN rs11730582 C>T polymorphism and cancer risk, but the results are inconsistent. Hence, a meta-analysis was conducted to determine the association of this polymorphism with cancer risk. Materials and methods The related articles were searched in PubMed, Embase, and Chinese National Knowledge Infrastructure databases. Pooled odds ratios and 95% confidence intervals were calculated to evaluate the strength of the associations. A random-effects model or fixed-effects model was employed depending on the heterogeneity. Results A total of ten case-control studies involving 2,749 cancer cases and 3,398 controls were included in the meta-analysis. In overall analysis, OPN rs11730582 C.T polymorphism was not associated with cancer risk. In a stratified analysis by cancer type, no significant association was found between OPN rs11730582 C>T polymorphism and the risk of glioma, gastric cancer, and other cancers. Conclusion This meta-analysis suggests that OPN rs11730582 C.T polymorphism is not associated with cancer susceptibility. PMID:27022284

  5. NAT2 polymorphisms combining with smoking associated with breast cancer susceptibility: a meta-analysis.

    PubMed

    Zhang, Jian; Qiu, Li-Xin; Wang, Zhong-Hua; Wang, Jia-Lei; He, Shuang-Shuang; Hu, Xi-Chun

    2010-10-01

    To derive a more precise estimation of the relationship between the slow or rapid acetylation resulting from N-acetyltransferase 2 (NAT2) polymorphisms and breast cancer risk, a meta-analysis was performed. PubMed, Medline, Embase, and Web of Science were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess strength of association. The pooled ORs were performed for slow versus rapid acetylation genotypes. A total of 26 studies including 9,215 cases and 10,443 controls were included in the meta-analysis. Overall, no significantly elevated breast cancer risk was associated with NAT2 slow genotypes when all studies were pooled into the meta-analysis (OR = 1.026, 95% CI = 0.968-1.087). In the subgroup analysis by ethnicity, increased risks were not found for either Caucasians (OR = 1.001, 95% CI = 0.938-1.068) or Asians (OR = 1.155, 95% CI = 0.886-1.506). When stratified by study design, statistically significantly elevated risk associated with NAT2 slow genotypes was only found among hospital-based studies (OR = 1.178, 95% CI = 1.037-1.339). In the subgroup analysis by menopausal status, no statistically significantly increased risk was found in either premenopausal (OR = 1.053, 95% CI = 0.886-1.252) or postmenopausal women (OR = 0.965, 95% CI = 0.844-1.104). When stratified by cumulative smoking exposure, in the subgroup of smokers with high pack-years, NAT2 slow genotypes were significantly associated with increased breast cancer risk (OR = 1.400, 95% CI = 1.099-1.784). In conclusion, this meta-analysis suggested that there is overall lack of association between NAT2 genotypes and breast cancer risk, however, NAT2 polymorphisms when combining with heavy smoking history may contribute to breast cancer susceptibility. PMID:20180012

  6. Meta-Analysis of Gene Level Tests for Rare Variant Association

    PubMed Central

    Liu, Dajiang J.; Peloso, Gina M.; Zhan, Xiaowei; Holmen, Oddgeir L.; Zawistowski, Matthew; Feng, Shuang; Nikpay, Majid; Auer, Paul L.; Goel, Anuj; Zhang, He; Peters, Ulrike; Farrall, Martin; Orho-Melander, Marju; Kooperberg, Charles; McPherson, Ruth; Watkins, Hugh; Willer, Cristen J.; Hveem, Kristian; Melander, Olle; Kathiresan, Sekar; Abecasis, Gonçalo R.

    2014-01-01

    The vast majority of connections between complex disease and common genetic variants were identified through meta-analysis, a powerful approach that enables large sample sizes while protecting against common artifacts due to population structure, repeated small sample analyses, and/or limitations with sharing individual level data. As the focus of genetic association studies shifts to rare variants, genes and other functional units are becoming the unit of analysis. Here, we propose and evaluate new approaches for performing meta-analysis of rare variant association tests, including burden tests, weighted burden tests, variable threshold tests and tests that allow variants with opposite effects to be grouped together. We show that our approach retains useful features of single variant meta-analytic approaches and demonstrate its utility in a study of blood lipid levels in ∼18,500 individuals genotyped with exome arrays. PMID:24336170

  7. Meta-analysis of the association between selenium and gastric cancer risk.

    PubMed

    Gong, He-Yi; He, Jin-Guang; Li, Bao-Sheng

    2016-03-29

    To clarify the effects of selenium level on the risk of gastric cancer (GC) and GC mortality, a meta-analysis was performed. Related studies were identified from PubMed, EMBASE, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM). Pooled ORs and 95% CIs were used to assess the strengthof the associations. A total of 8 studies including 17834 subjects were involved in this meta-analysis. High selenium level was associated with GC risk in case-control study (OR = 0.62, 95% CI 0.44-0.89, P = 0.009; I2 = 52%) and cohort study (OR = 0.87, 95% CI 0.78-0.97, P = 0.01; I2 = 25%). In addition, high selenium level was associated with GC mortality risk (OR = 0.90, 95% CI 0.84-0.97, P = 0.006, I2 = 49%). In summary, this meta-analysis suggested that selenium might inversely associated with GC risk and GC mortality. PMID:26862854

  8. A meta-analysis of association between acne ulgaris and Demodex infestation*

    PubMed Central

    Zhao, Ya-e; Hu, Li; Wu, Li-ping; Ma, Jun-xian

    2012-01-01

    Until now, etiology of acne vulgaris is still uncertain. Although clinicians usually deny the association between Demodex infestation and acne vulgaris, it has been proved in some clinical practices. To confirm the association between Demodex infestation and acne vulgaris, a meta-analysis was conducted. Predefined selection criteria were applied to search all published papers that analyzed the association between Demodex infestation and acne vulgaris (January 1950 to August 2011) in ISI Web of Knowledge, MEDLINE, and China National Knowledge Infrastructure (CNKI) databases. A meta-analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) based on fixed effects models or random effects models. We enrolled the 60 Chinese and 3 English papers in this meta-analysis, which covered Turkey and 25 different provinces/municipalities in China and 42 130 participants including students and residents, aged from 1 to 78 years. The pooled OR in random effects models is 2.80 (95% CI, 2.34–3.36). Stability is robust according to sensitivity analysis. The fail-safe number is 18 477, suggesting that at least 18 477 articles with negative conclusions would be needed to reverse the conclusion that acne vulgaris was related to Demodex infestation. So the effect of publication bias was insignificant and could be ignored. It was concluded that acne vulgaris is associated with Demodex infestation. This indicates that when regular treatments for acne vulgaris are ineffective, examination of Demodex mites and necessary acaricidal therapies should be considered. PMID:22374611

  9. Association between seminal plasma zinc level and asthenozoospermia: a meta-analysis study.

    PubMed

    Taravati, A; Tohidi, F

    2016-08-01

    Zinc is proposed to have an important role in the morphology, viability and motility of spermatozoa. There are inconsistent reports on the association between seminal plasma zinc concentration and male infertility. For this purpose, papers reporting the level of seminal zinc among asthenozoospermic groups were selected and used for further analysis. This meta-analysis of previous published studies was performed to obtain more precise information on the association between seminal plasma zinc and asthenozoospermia. Relevant studies for inclusion were identified after preliminary investigation of research papers published on electronic databases up to February 2015. Eight reports and 475 subjects were finally included in the meta-analysis. In the overall analysis, a statistically significant reduction in seminal plasma zinc concentrations was observed in asthenozoospermic infertile men. Random-effects method was used to evaluate the summary effect size due to the presence of significant heterogeneity. The effect of zinc on asthenozoospermia was significant (Hedge's G effect size = -0.506, 95% confidence interval (95% CI): -0.998 to -0.014, P = 0.044). Taken together, despite of significant statistical heterogeneity between studies, our findings were indicative of significant association between zinc concentration and asthenozoospermia. In conclusion, the meta-analysis suggests that seminal plasma zinc concentration is negatively associated with male infertility. PMID:26541500

  10. MetaSeq: privacy preserving meta-analysis of sequencing-based association studies.

    PubMed

    Singh, Angad Pal; Zafer, Samreen; Pe'er, Itsik

    2013-01-01

    Human genetics recently transitioned from GWAS to studies based on NGS data. For GWAS, small effects dictated large sample sizes, typically made possible through meta-analysis by exchanging summary statistics across consortia. NGS studies groupwise-test for association of multiple potentially-causal alleles along each gene. They are subject to similar power constraints and therefore likely to resort to meta-analysis as well. The problem arises when considering privacy of the genetic information during the data-exchange process. Many scoring schemes for NGS association rely on the frequency of each variant thus requiring the exchange of identity of the sequenced variant. As such variants are often rare, potentially revealing the identity of their carriers and jeopardizing privacy. We have thus developed MetaSeq, a protocol for meta-analysis of genome-wide sequencing data by multiple collaborating parties, scoring association for rare variants pooled per gene across all parties. We tackle the challenge of tallying frequency counts of rare, sequenced alleles, for metaanalysis of sequencing data without disclosing the allele identity and counts, thereby protecting sample identity. This apparent paradoxical exchange of information is achieved through cryptographic means. The key idea is that parties encrypt identity of genes and variants. When they transfer information about frequency counts in cases and controls, the exchanged data does not convey the identity of a mutation and therefore does not expose carrier identity. The exchange relies on a 3rd party, trusted to follow the protocol although not trusted to learn about the raw data. We show applicability of this method to publicly available exome-sequencing data from multiple studies, simulating phenotypic information for powerful meta-analysis. The MetaSeq software is publicly available as open source. PMID:23424140

  11. The association between Helicobacter pylori infection and inflammatory bowel disease based on meta-analysis

    PubMed Central

    Gisbert, JP; Niv, Y; O’Morain, C

    2015-01-01

    Background In humans there are epidemiological data suggesting a protective effect of Helicobacter pylori (H. pylori) infection against the development of autoimmune diseases and in addition, there are laboratory data illustrating H. pylori’s ability to induce immune tolerance and limit inflammatory responses. Thus, numerous observational studies have examined the association between H. pylori infection and inflammatory bowel disease (IBD) with various results. Objective We performed a meta-analysis of available studies to better define the association of H. pylori infection and IBD. Methods Medical literature searches for human studies were performed through September 2014, using suitable keywords. In each study the risk ratio (RR) of H. pylori infection in IBD patients vs controls was calculated and pooled estimates were obtained using fixed- or random-effects models as appropriate. Heterogeneity between studies was evaluated using Cochran Q test and I2 statistics, whereas the likelihood of publication bias was assessed by constructing funnel plots. Results Thirty-three studies were eligible for meta-analysis, including 4400 IBD patients and 4763 controls. Overall 26.5% of IBD patients were positive for H. pylori infection, compared to 44.7% of individuals in the control group. There was significant heterogeneity in the included studies (Q = 137.2, df (Q) =32, I2 = 77%, p < 0.001) and therefore the random-effects model of meta-analysis was used. The obtained pool RR estimation was 0.62 (95% confidence interval (CI) 0.55–0.71, test for overall effect Z = –7.04, p < 0.001). There was no evidence of publication bias. Conclusion The results of this meta-analysis showed a significant negative association between H. pylori infection and IBD that supports a possible protective benefit of H. pylori infection against the development of IBD. PMID:26668747

  12. Association of maternal AGTR1 polymorphisms and preeclampsia: a systematic review and meta-analysis

    PubMed Central

    Zhao, Linlu; Dewan, Andrew T.; Bracken, Michael B.

    2013-01-01

    Objective Systematic review and meta-analysis to investigate the association between maternal AGTR1 gene single nucleotide polymorphisms (SNPs) and preeclampsia (PE). Methods A systematic literature search was performed using PubMed, EMBASE, Scopus, and HuGE Literature Finder databases. The review was conducted according to PRISMA guidelines. Summary odds ratios (ORs) for the allelic and genotypic contrasts were calculated and compared to indicate the most appropriate genetic model for the polymorphism of interest. Among-study heterogeneity was assessed using the I2 statistic and publication bias was evaluated visually using funnel plots. Results Seven maternal SNPs investigated with PE were found, but only AGTR1 +1166A>C accumulated sufficient evidence for meta-analysis. Summary ORs calculated from eight studies (10 populations involving 845 PE cases and 1150 controls) did not reveal an association between the +1166A>C polymorphism and PE (allelic OR = 1.19, 95% CI: 0.96–1.47). No evidence of publication bias and among-study heterogeneity was detected. Conclusions Meta-analysis findings did not support AGTR1 +1166A>C as a susceptibility locus for PE. Other AGTR1 SNPs require more study. PMID:22758920

  13. Association Between BRCA Status and P53 Status in Breast Cancer: A Meta-Analysis.

    PubMed

    Peng, Lin; Xu, Tao; Long, Ting; Zuo, Huaiquan

    2016-01-01

    BACKGROUND Research on BRCA mutation has meaningful clinical implications, such as identifying risk of second primary cancers and risk of hereditary cancers. This study seeks to summarize available data to investigate the association between BRCA status and P53 status by meta-analysis. MATERIAL AND METHODS We searched PubMed, Embase, and Cochrane library databases for relevant studies. Meta-analysis was conducted using STATA software. We summarized odds ratios by fixed-effects or random-effects models. RESULTS This study included a total of 4288 cases from 16 articles, which including 681 BRCA1 mutation carriers (BRCA1Mut), 366 carriers of BRCA2 mutation (BRCA2Mut), and 3241 carriers of normal versions of these genes. BRCA1Mut was significantly associated with P53 over-expression compared with BRCA2Mut (OR 1.851, 95% CI=1.393-2.458) or non-carriers (OR=2.503, 95% CI=1.493-4.198). No difference was found between p53 protein expression in BRCA2 Mut carriers and non-carriers (OR=0.881, 95% CI=0.670-1.158). CONCLUSIONS Our meta-analysis suggests that BRCA1Mut breast cancer patients are more likely to have P53 overexpression compared with BRCA2Mut and non-carriers. This information provides valuable information for clinicians who perform related studies in the future. PMID:27272763

  14. Association Between BRCA Status and P53 Status in Breast Cancer: A Meta-Analysis

    PubMed Central

    Peng, Lin; Xu, Tao; Long, Ting; Zuo, Huaiquan

    2016-01-01

    Background Research on BRCA mutation has meaningful clinical implications, such as identifying risk of second primary cancers and risk of hereditary cancers. This study seeks to summarize available data to investigate the association between BRCA status and P53 status by meta-analysis. Material/Methods We searched PubMed, Embase, and Cochrane library databases for relevant studies. Meta-analysis was conducted using STATA software. We summarized odds ratios by fixed-effects or random-effects models. Results This study included a total of 4288 cases from 16 articles, which including 681 BRCA1 mutation carriers (BRCA1Mut), 366 carriers of BRCA2 mutation (BRCA2Mut), and 3241 carriers of normal versions of these genes. BRCA1Mut was significantly associated with P53 over-expression compared with BRCA2Mut (OR 1.851, 95% CI=1.393–2.458) or non-carriers (OR=2.503, 95% CI=1.493–4.198). No difference was found between p53 protein expression in BRCA2 Mut carriers and non-carriers (OR=0.881, 95% CI=0.670–1.158). Conclusions Our meta-analysis suggests that BRCA1Mut breast cancer patients are more likely to have P53 overexpression compared with BRCA2Mut and non-carriers. This information provides valuable information for clinicians who perform related studies in the future. PMID:27272763

  15. Association between diabetes mellitus and gastroesophageal reflux disease: A meta-analysis

    PubMed Central

    Sun, Xiao-Meng; Tan, Jia-Cheng; Zhu, Ying; Lin, Lin

    2015-01-01

    AIM: To investigate whether there is a link between diabetes mellitus (DM) and gastroesophageal reflux disease (GERD). METHODS: We conducted a systematic search of PubMed and Web of Science databases, from their respective inceptions until December 31, 2013, for articles evaluating the relationship between DM and GERD. Studies were selected for analysis based on certain inclusion and exclusion criteria. Data were extracted from each study on the basis of predefined items. A meta-analysis was performed to compare the odds ratio (OR) in DM between individuals with and without GERD using a fixed effect or random effect model, depending on the absence or presence of significant heterogeneity. Subgroup analyses were used to identify sources of heterogeneity. Publication bias was assessed by Begg’s test. To evaluate the results, we also performed a sensitivity analysis. RESULTS: When the electronic database and hand searches were combined, a total of nine eligible articles involving 9067 cases and 81 968 controls were included in our meta-analysis. Based on the random-effects model, these studies identified a significant association between DM and the risk of GERD (overall OR = 1.61; 95%CI: 1.36-1.91; P = 0.003). Subgroup analyses indicated that this result persisted in studies on populations from Eastern countries (OR = 1.71; 95%CI: 1.38-2.12; P = 0.003) and in younger patients (mean age < 50 years) (OR = 1.70; 95%CI: 1.22-2.37; P = 0.001). No significant publication bias was observed in this meta-analysis using Begg’s test (P = 0.175). The sensitivity analysis also confirmed the stability of our results. CONCLUSION: This meta-analysis suggests that patients with DM are at greater risk of GERD than those who do not have DM. PMID:25780309

  16. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height

    PubMed Central

    Lanktree, Matthew B.; Guo, Yiran; Murtaza, Muhammed; Glessner, Joseph T.; Bailey, Swneke D.; Onland-Moret, N. Charlotte; Lettre, Guillaume; Ongen, Halit; Rajagopalan, Ramakrishnan; Johnson, Toby; Shen, Haiqing; Nelson, Christopher P.; Klopp, Norman; Baumert, Jens; Padmanabhan, Sandosh; Pankratz, Nathan; Pankow, James S.; Shah, Sonia; Taylor, Kira; Barnard, John; Peters, Bas J.; M. Maloney, Cliona; Lobmeyer, Maximilian T.; Stanton, Alice; Zafarmand, M. Hadi; Romaine, Simon P.R.; Mehta, Amar; van Iperen, Erik P.A.; Gong, Yan; Price, Tom S.; Smith, Erin N.; Kim, Cecilia E.; Li, Yun R.; Asselbergs, Folkert W.; Atwood, Larry D.; Bailey, Kristian M.; Bhatt, Deepak; Bauer, Florianne; Behr, Elijah R.; Bhangale, Tushar; Boer, Jolanda M.A.; Boehm, Bernhard O.; Bradfield, Jonathan P.; Brown, Morris; Braund, Peter S.; Burton, Paul R.; Carty, Cara; Chandrupatla, Hareesh R.; Chen, Wei; Connell, John; Dalgeorgou, Chrysoula; Boer, Anthonius de; Drenos, Fotios; Elbers, Clara C.; Fang, James C.; Fox, Caroline S.; Frackelton, Edward C.; Fuchs, Barry; Furlong, Clement E.; Gibson, Quince; Gieger, Christian; Goel, Anuj; Grobbee, Diederik E.; Hastie, Claire; Howard, Philip J.; Huang, Guan-Hua; Johnson, W. Craig; Li, Qing; Kleber, Marcus E.; Klein, Barbara E.K.; Klein, Ronald; Kooperberg, Charles; Ky, Bonnie; LaCroix, Andrea; Lanken, Paul; Lathrop, Mark; Li, Mingyao; Marshall, Vanessa; Melander, Olle; Mentch, Frank D.; J. Meyer, Nuala; Monda, Keri L.; Montpetit, Alexandre; Murugesan, Gurunathan; Nakayama, Karen; Nondahl, Dave; Onipinla, Abiodun; Rafelt, Suzanne; Newhouse, Stephen J.; Otieno, F. George; Patel, Sanjey R.; Putt, Mary E.; Rodriguez, Santiago; Safa, Radwan N.; Sawyer, Douglas B.; Schreiner, Pamela J.; Simpson, Claire; Sivapalaratnam, Suthesh; Srinivasan, Sathanur R.; Suver, Christine; Swergold, Gary; Sweitzer, Nancy K.; Thomas, Kelly A.; Thorand, Barbara; Timpson, Nicholas J.; Tischfield, Sam; Tobin, Martin; Tomaszweski, Maciej; Verschuren, W.M. Monique; Wallace, Chris; Winkelmann, Bernhard; Zhang, Haitao; Zheng, Dongling; Zhang, Li; Zmuda, Joseph M.; Clarke, Robert; Balmforth, Anthony J.; Danesh, John; Day, Ian N.; Schork, Nicholas J.; de Bakker, Paul I.W.; Delles, Christian; Duggan, David; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofker, Marten H.; Humphries, Steve E.; Kivimaki, Mika; Lawlor, Debbie A.; Kottke-Marchant, Kandice; Mega, Jessica L.; Mitchell, Braxton D.; Morrow, David A.; Palmen, Jutta; Redline, Susan; Shields, Denis C.; Shuldiner, Alan R.; Sleiman, Patrick M.; Smith, George Davey; Farrall, Martin; Jamshidi, Yalda; Christiani, David C.; Casas, Juan P.; Hall, Alistair S.; Doevendans, Pieter A.; D. Christie, Jason; Berenson, Gerald S.; Murray, Sarah S.; Illig, Thomas; Dorn, Gerald W.; Cappola, Thomas P.; Boerwinkle, Eric; Sever, Peter; Rader, Daniel J.; Reilly, Muredach P.; Caulfield, Mark; Talmud, Philippa J.; Topol, Eric; Engert, James C.; Wang, Kai; Dominiczak, Anna; Hamsten, Anders; Curtis, Sean P.; Silverstein, Roy L.; Lange, Leslie A.; Sabatine, Marc S.; Trip, Mieke; Saleheen, Danish; Peden, John F.; Cruickshanks, Karen J.; März, Winfried; O'Connell, Jeffrey R.; Klungel, Olaf H.; Wijmenga, Cisca; Maitland-van der Zee, Anke Hilse; Schadt, Eric E.; Johnson, Julie A.; Jarvik, Gail P.; Papanicolaou, George J.; Grant, Struan F.A.; Munroe, Patricia B.; North, Kari E.; Samani, Nilesh J.; Koenig, Wolfgang; Gaunt, Tom R.; Anand, Sonia S.; van der Schouw, Yvonne T.; Soranzo, Nicole; FitzGerald, Garret A.; Reiner, Alex; Hegele, Robert A.; Hakonarson, Hakon; Keating, Brendan J.

    2011-01-01

    Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10−6), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10−8). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10−11). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait. PMID:21194676

  17. Association of HLA and post-schistosomal hepatic disorder: a systematic review and meta-analysis.

    PubMed

    Huy, Nguyen Tien; Hamada, Mohamed; Kikuchi, Mihoko; Lan, Nguyen Thi Phuong; Yasunami, Michio; Zamora, Javier; Hirayama, Kenji

    2011-12-01

    Several human genetic variants, HLA antigens and alleles are reportedly linked to post-schistosomal hepatic disorder (PSHD), but the results from these reports are highly inconclusive. In order to estimate overall associations between human genetic variants, HLA antigens, HLA alleles and PSHD, we systematically reviewed and performed a meta-analysis of relevant studies in both post-schistosomal hepatic disorder and post-schistosomal non-hepatic disorder patients. PubMed, Scopus, Google Scholar, The HuGE Published Literature database, Cochrane Library, and manual search of reference lists of articles published before July 2009 were used to retrieve relevant studies. Two reviewers independently selected articles and extracted data on study characteristics and data regarding the association between genetic variants, HLA antigens, HLA alleles and PSHD in the form of 2×2 tables. A meta-analysis using fixed-effects or random-effects models to pooled odds ratios (OR) with corresponding 95% confidence intervals were calculated only if more than one study had investigated particular variation. We found 17 articles that met our eligibility criteria. Schistosoma mansoni and Schistosoma japonicum were reported as the species causing PSHD. Since human genetic variants were only investigated in one study, these markers were not assessed by meta-analysis. Thus, only HLA-genes (a total of 66 HLA markers) were conducted in the meta-analysis. Our meta-analysis showed that human leucocyte antigens HLA-DQB1*0201 (OR=2.64, P=0.018), DQB1*0303 (OR=1.93, P=0.008), and DRB1*0901 (OR=2.14, P=0.002) alleles and HLA-A1 (OR=5.10, P=0.001), A2 (OR=2.17, P=0.005), B5 (OR=4.63, P=0.001), B8 (OR=2.99, P=0.02), and B12 (OR=5.49, P=0.005) serotypes enhanced susceptibility to PSHD, whereas HLA-DQA1*0501 (OR=0.29, P≤0.001) and DQB1*0301 (OR=0.58, P=0.007) were protective factors against the disease. We further suggested that the DRB1*0901-DQB1*0201, DRB1*0901-DQB1*0303 and A1-B8 haplotypes

  18. Association of rs6983267 Polymorphism and Thyroid Cancer Susceptibility: A Systematic Review and Meta-Analysis

    PubMed Central

    Li, Jingdong; Wang, Xiaofei; Dong, Jiahong

    2016-01-01

    Background Recent genome-wide association studies have identified rs6983267 polymorphism as a key locus in the 8q24 region associated with multisite cancers. However, the information on its association with thyroid cancer is inconclusive. The aim of this study was to determine whether this locus is a risk factor for susceptibility to thyroid cancer by conducting a meta-analysis. Material/Methods Relevant studies were identified by searching PubMed and Embase databases. The pooled odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated. Results A total of 4 studies including 2825 cases and 9684 controls were enrolled to this meta-analysis. The pooled data showed the G allele of the rs6983267 polymorphism is a risk factor for susceptibility to thyroid cancer (OR=1.08, 95%CI: 1.02–1.16, P=0.01). Significant associations were also found in homozygote comparison (GG vs. TT: OR=1.17, 95%CI: 1.03–1.33, P=0.02) and dominant model (GG+GT vs. TT: OR=1.13, 95%CI: 1.01–1.26, P=0.03). Borderline significant associations in similar directions were found in the recessive model (GG vs. GT+TT: OR=1.10, 95%CI: 0.99–1.22, P=0.07) and heterozygote comparison (GT vs. TT: OR=1.10, 95%CI: 0.99–1.24, P=0.09). Conclusions Our meta-analysis shows that the rs6983267 G>T polymorphism might be associated with higher risk of thyroid cancer. Further research with larger sample sizes and full investigation of confounding risk factors is needed to confirm or revise our conclusions. PMID:27251952

  19. Association of rs6983267 Polymorphism and Thyroid Cancer Susceptibility: A Systematic Review and Meta-Analysis.

    PubMed

    Li, Jingdong; Wang, Xiaofei; Dong, Jiahong

    2016-01-01

    BACKGROUND Recent genome-wide association studies have identified rs6983267 polymorphism as a key locus in the 8q24 region associated with multisite cancers. However, the information on its association with thyroid cancer is inconclusive. The aim of this study was to determine whether this locus is a risk factor for susceptibility to thyroid cancer by conducting a meta-analysis. MATERIAL AND METHODS Relevant studies were identified by searching PubMed and Embase databases. The pooled odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated. RESULTS A total of 4 studies including 2825 cases and 9684 controls were enrolled to this meta-analysis. The pooled data showed the G allele of the rs6983267 polymorphism is a risk factor for susceptibility to thyroid cancer (OR=1.08, 95%CI: 1.02-1.16, P=0.01). Significant associations were also found in homozygote comparison (GG vs. TT: OR=1.17, 95%CI: 1.03-1.33, P=0.02) and dominant model (GG+GT vs. TT: OR=1.13, 95%CI: 1.01-1.26, P=0.03). Borderline significant associations in similar directions were found in the recessive model (GG vs. GT+TT: OR=1.10, 95%CI: 0.99-1.22, P=0.07) and heterozygote comparison (GT vs. TT: OR=1.10, 95%CI: 0.99-1.24, P=0.09). CONCLUSIONS Our meta-analysis shows that the rs6983267 G>T polymorphism might be associated with higher risk of thyroid cancer. Further research with larger sample sizes and full investigation of confounding risk factors is needed to confirm or revise our conclusions. PMID:27251952

  20. Association between Asthma and Autism Spectrum Disorder: A Meta-Analysis

    PubMed Central

    Zheng, Zhen; Zhang, Li; Zhu, Tingting; Huang, Jichong; Qu, Yi; Mu, Dezhi

    2016-01-01

    Objective We conducted a meta-analysis to summarize the evidence from epidemiological studies of the association between asthma and autism spectrum disorder (ASD). Methods A literature search was conducted using PubMed, Embase, and Cochrane library for studies published before February 2nd, 2016. Observational studies investigating the association between asthma and ASD were included. A random effects model was used to calculate the pooled risk estimates for the outcome. Subgroup analysis was used to explore potential sources of heterogeneity and publication bias was estimated using Begg's and Egger's tests. Results Ten studies encompassing 175,406 participants and 8,809 cases of ASD were included in this meta-analysis. In the cross-sectional studies, the prevalence of asthma in ASD was 20.4%, while the prevalence of asthma in controls was 15.4% (P < 0.001). The pooled odds ratio (OR) for the prevalence of asthma in ASD in the cross-sectional studies was 1.26 (95% confidence interval (CI): 0.98–1.61) (P = 0.07), with moderate heterogeneity (I2 = 65.0%, P = 0.02) across studies. In the case-control studies, the pooled OR for the prevalence of asthma in ASD was 0.98 (95% CI: 0.68–1.43) (P = 0.94), and there was no evidence of an association between asthma and ASD. No evidence of significant publication bias on the association between asthma and ASD was found. Conclusions In conclusion, the results of this meta-analysis do not suggest an association between asthma and ASD. Further prospective studies ascertaining the association between asthma and ASD are warranted. PMID:27257919

  1. Association between methylenetetrahydrofolate reductase C677T polymorphism and psoriasis: A meta-analysis.

    PubMed

    Wu, Dongze; Shi, Deshun; Yang, Li; Zhu, Xiaoliang

    2016-02-01

    Several studies have evaluated the associations between methylenetetrahydrofolate reductase (MTHFR) C677T and psoriasis. However, the results remain inconclusive. The objective of the present study was to conduct a qualitative and quantitative meta-analysis investigating the associations between MTHFR C677T and psoriasis. A published work search of PubMed, Embase, Web of Science and Chinese National Knowledge Infrastructure database were conducted to identify all publications concerning MTHFR C677T polymorphism and psoriasis on 1 October 2014. The principal outcome measure for evaluating the strength of the association was crude odds ratios along with their corresponding 95% confidence intervals. Data were extracted and statistical analyses were implemented using STATA version 12.0 software. A total of 1179 psoriatic cases and 937 controls from five case-control studies concentrating on the association between MTHFR C677T polymorphism and psoriasis were included in this qualitative meta-analysis. Pooled analysis revealed that there is no association between this polymorphism and susceptibility to psoriasis in dominant, recessive, allele and additive models under a random-effect model. However, a marginal significant association was found in the overdominant model under fixed-effect model. Subgroup analysis of ethnicity demonstrated that there is no association between MTHFR C677T polymorphism and either Asian or European psoriatic patients. In conclusion, MTHFR C677T polymorphism, qualitatively, is not a genetic factor for the pathogenesis of psoriasis but could quantitatively reflect the severity of psoriasis to some extent. PMID:26212228

  2. Association of Vitamin D Receptor Cdx-2 Polymorphism With Cancer Risk: A Meta-Analysis.

    PubMed

    Dai, Zhi-Ming; Fei, Yu-Lang; Zhang, Wang-Gang; Liu, Jie; Cao, Xing-Mei; Qu, Qiu-Min; Li, Yan-Chun; Lin, Shuai; Wang, Meng; Dai, Zhi-Jun

    2015-08-01

    Vitamin D receptor (VDR) Cdx-2 polymorphism (rs11568820) has been indicated to be associated to cancer susceptibility. However, published studies reported mixed results. This meta-analysis was conducted to get a more accurate estimation of the association between Cdx-2 polymorphism and cancer risk.We identified 25 independent studies with a total of 34,018 subjects published prior to March 2015. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to cancer. Separate analyses were conducted on features of the population such as ethnicity, source of controls, and cancer types.Meta-analysis results showed that Cdx-2 polymorphism significantly increased cancer risk in the homozygous model in overall analysis. According to the further stratified analysis, significant association was found between Cdx-2 variant and cancer risk in American-Africans in the homozygous, recessive, and dominant comparison models. However, no significant associations were found in Caucasians and Asians. When stratified by different cancer types, significant association was observed between Cdx-2 variant and an increased risk of colorectal cancer in the homozygous, recessive, and dominant models. In addition, ovarian cancer susceptibility increased based on the homozygous and dominant comparison models.Our study indicated that VDR Cdx-2 polymorphism was associated with an increased cancer risk, particularly in American-Africans, colorectal, and ovarian cancers. However, other factors may impact on the association. Further multicenter studies are needed to confirm the effects of Cdx-2 polymorphism on cancer susceptibility. PMID:26287424

  3. Association of HLA-DRB1 Gene Polymorphism with Risk of Asthma: A Meta-Analysis

    PubMed Central

    Yao, Yingshui; Zhu, Lijun; Li, Jie; Jin, Yuelong; He, Lianping

    2016-01-01

    Background The relationship between HLA-DRB1 alleles and asthma is controversial. The purpose of this study was to evaluate the relationship between HLA-DRB1 alleles and risk of asthma. Material/Methods We searched PubMed, Chinese National Knowledge Infrastructure (CNKI), Wan Fang (Chinese) database, and Chinese Biomedical Medical databases (CBM) to find studies on the relationship between HLA-DRB1 alleles and risk of asthma. We calculated the pooled odds ratio (OR) and 95% confidence interval (CI) using STATA 12.0. Finally, a total of 24 studies were included in this meta-analysis. Results The results revealed that DRB1*03 was positively associated with risk of asthma (OR=1.51, 95%CI=1.27–1.80), and DRB1*15 was negatively associated with risk of asthma (OR=0.63, 95%CI=0.42–0.93), but no association was found in other HLA-DRB1 alleles. Subgroup analysis by age revealed that DRB1*03, DRB1*04, DRB1*09, and DRB1*15 were associated with asthma in children. Subgroup analysis by ethnicity showed that DRB1*03 and DRB1*15 were associated with asthma in whites, and DRB1*07 and DRB1*14 were associated with asthma in Asians. Conclusions This results of this meta-analysis suggest that HLA-DRB1 alleles are associated with asthma. PMID:27503745

  4. Association of HLA-DRB1 Gene Polymorphism with Risk of Asthma: A Meta-Analysis.

    PubMed

    Yao, Yingshui; Zhu, Lijun; Li, Jie; Jin, Yuelong; He, Lianping

    2016-01-01

    BACKGROUND The relationship between HLA-DRB1 alleles and asthma is controversial. The purpose of this study was to evaluate the relationship between HLA-DRB1 alleles and risk of asthma. MATERIAL AND METHODS We searched PubMed, Chinese National Knowledge Infrastructure (CNKI), Wan Fang (Chinese) database, and Chinese Biomedical Medical databases (CBM) to find studies on the relationship between HLA-DRB1 alleles and risk of asthma. We calculated the pooled odds ratio (OR) and 95% confidence interval (CI) using STATA 12.0. Finally, a total of 24 studies were included in this meta-analysis. RESULTS The results revealed that DRB1*03 was positively associated with risk of asthma (OR=1.51, 95%CI=1.27-1.80), and DRB1*15 was negatively associated with risk of asthma (OR=0.63, 95%CI=0.42-0.93), but no association was found in other HLA-DRB1 alleles. Subgroup analysis by age revealed that DRB1*03, DRB1*04, DRB1*09, and DRB1*15 were associated with asthma in children. Subgroup analysis by ethnicity showed that DRB1*03 and DRB1*15 were associated with asthma in whites, and DRB1*07 and DRB1*14 were associated with asthma in Asians. CONCLUSIONS This results of this meta-analysis suggest that HLA-DRB1 alleles are associated with asthma. PMID:27503745

  5. Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis.

    PubMed

    Pu, Danhua; Shen, Yiping; Wu, Jie

    2013-10-01

    Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and the epigenetic process of DNA methylation, and its gene polymorphisms have been implicated as risk factors for birth defects, neurological disorders, and cancers. However, reports on the association of MTHFR polymorphisms with autism spectrum disorders (ASD) are inconclusive. Therefore, we investigated the relationship of the MTHFR polymorphisms (C677T and A1298C) and the risk of ASD by meta-analysis. Up to December 2012, eight case-control studies involving 1672 patients with ASD and 6760 controls were included for meta-analysis. The results showed that the C677T polymorphism was associated with significantly increased ASD risk in all the comparison models [T vs. C allele (frequency of allele): odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.09-1.85; CT vs. CC (heterozygote): OR = 1.48, 95% CI: 1.09-2.00; TT vs. CC (homozygote): OR = 1.86, 95% CI: 1.08-3.20; CT+TT vs. CC (dominant model): OR = 1.56, 95% CI: 1.12-2.18; and TT vs. CC+CT (recessive model): OR = 1.51, 95% CI: 1.02-2.22], whereas the A1298C polymorphism was found to be significantly associated with reduced ASD risk but only in a recessive model (CC vs. AA+AC: OR = 0.73, 95% CI: 0.56-0.97). In addition, we stratified the patient population based on whether they were from a country with food fortification of folic acid or not. The meta-analysis showed that the C677T polymorphism was found to be associated with ASD only in children from countries without food fortification. Our study indicated that the MTHFR C677T polymorphism contributes to increased ASD risk, and periconceptional folic acid may reduce ASD risk in those with MTHFR 677C>T polymorphism. PMID:23653228

  6. Association of Interleukin-23 receptor gene polymorphisms with susceptibility to Crohn’s disease: A meta-analysis

    PubMed Central

    Xu, Wang-Dong; Xie, Qi-Bing; Zhao, Yi; Liu, Yi

    2015-01-01

    Studies investigating the association between Interleukin-23 receptor (IL-23R) gene polymorphisms and Crohn’s disease (CD) report conflicting results. Thus, a meta-analysis was carried out to assess the association between the IL-23R polymorphisms and CD. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratio (ORs) with 95% confidence interval (CIs) was used to estimate the strength of association. Finally, a total of 60 case-control studies in 56 articles, involving 22,820 CD patients and 27,401 healthy controls, were included in the meta-analysis. Overall, a significant association was found between all CD and the rs7517847 polymorphism (OR = 0.699, 95% CI = 0.659 ~ 0.741, P < 0.001). Meta-analysis of the rs11209026, rs1343151, rs10489629 and rs11465804 polymorphisms indicated the same pattern as for rs7517847. Meta-analysis showed an association between the rs10889677A allele and CD (OR = 1.393, 95% CI = 1.328 ~ 1.461, P < 0.001). Similarly, meta-analysis of the rs2201840, rs1004819, rs1495965 and rs11209032 polymorphisms revealed the same pattern as that shown by meta-analysis of rs10889677. Stratification by ethnicity revealed that IL-23R gene polymorphisms were associated with CD in the Caucasian group, but not in Asians. In summary, the meta-analysis suggests a significant association between IL-23R polymorphisms and CD, especially in Caucasians. PMID:26678098

  7. Meta-Analysis of the Association between Mir-196a-2 Polymorphism and Cancer Susceptibility

    PubMed Central

    Zhang, Huan; Su, Yu-liang; Yu, Herbert; Qian, Bi-yun

    2012-01-01

    Objective MicroRNA plays a vital role in gene expression, and microRNA dysregulation is involved in carcinogenesis. The miR-196a-2 polymorphism rs11614913 is reportedly associated with cancer susceptibility. This meta-analysis was performed to assess the overall association of miR-196a-2 with cancer risk. Methods A total of 27 independent case-control studies involving 10,435 cases and 12,075 controls were analyzed for the rs11614913 polymorphism. Results A significant association was found between rs11614913 polymorphism and cancer risk in four genetic models (CT vs. TT, OR=1.15, 95%CI=1.05–1.27; CC vs. TT, OR=1.23, 95%CI=1.08–1.39; Dominant model, OR=1.17, 95%CI=1.06–1.30; Additive model, OR=1.08, 95%CI=1.01–1.14). In the subgroup analysis of different tumor types, the C allele was associated with increased risk of lung, breast, and colorectal cancer, but not with liver, gastric, or esophageal cancer. In the subgroup analysis by ethnicity, a significantly increased risk of cancer was found among Asians in all genetic models, but no associations were found in the Caucasian subgroup. Conclusions The meta-analysis demonstrated that the miR-196a-2 polymorphism is associated with cancer susceptibility, especially lung cancer, colorectal cancer, and breast cancer among Asian populations. PMID:23691458

  8. Is hypertension associated with job strain? A meta-analysis of observational studies.

    PubMed

    Babu, Giridhara R; Jotheeswaran, A T; Mahapatra, Tanmay; Mahapatra, Sanchita; Kumar, Ananth; Detels, Roger; Pearce, Neil

    2014-07-01

    Job strain results from a combination of high workload and few decision-making opportunities in the workplace. There is inconsistent evidence regarding the association between job strain and hypertension, and methodological shortcomings preclude firm conclusions. Thus, a meta-analysis of observational studies on hypertension among occupational groups was conducted to determine whether job strain was associated with hypertension. In January 2012, we carried out a comprehensive, topic-specific electronic literature search of the Ovid MEDLINE, EMBASE and PsychoINFO databases complemented by individual help from non-communicable disease experts. Experimental/interventional studies and studies on personality disorders were excluded. Nine of 894 identified studies met the eligibility criteria and were included in the meta-analysis. The pooled OR of the nine studies was 1.3 (95% CI 1.14 to 1.48; p<0.001), of case-control studies 3.17 (95% CI 1.79 to 5.60; p<0.001) and of cohort studies 1.24 (95% CI 1.09 to 1.41; p<0.001), all of which indicated statistically significant positive associations between job strain and hypertension. In a subgroup analysis, cohort studies of good methodological quality showed significant associations between job strain and hypertension, while those of poor methodological quality showed no association or subgroup differences. We conclude that despite methodological differences, case-control and cohort studies of good methodological quality showed positive associations between hypertension and job strain. PMID:24942354

  9. SecureMA: protecting participant privacy in genetic association meta-analysis

    PubMed Central

    Xie, Wei; Kantarcioglu, Murat; Bush, William S.; Crawford, Dana; Denny, Joshua C.; Heatherly, Raymond; Malin, Bradley A.

    2014-01-01

    Motivation: Sharing genomic data is crucial to support scientific investigation such as genome-wide association studies. However, recent investigations suggest the privacy of the individual participants in these studies can be compromised, leading to serious concerns and consequences, such as overly restricted access to data. Results: We introduce a novel cryptographic strategy to securely perform meta-analysis for genetic association studies in large consortia. Our methodology is useful for supporting joint studies among disparate data sites, where privacy or confidentiality is of concern. We validate our method using three multisite association studies. Our research shows that genetic associations can be analyzed efficiently and accurately across substudy sites, without leaking information on individual participants and site-level association summaries. Availability and implementation: Our software for secure meta-analysis of genetic association studies, SecureMA, is publicly available at http://github.com/XieConnect/SecureMA. Our customized secure computation framework is also publicly available at http://github.com/XieConnect/CircuitService Contact: b.malin@vanderbilt.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25147357

  10. Factors Associated with Dengue Shock Syndrome: A Systematic Review and Meta-Analysis

    PubMed Central

    Thuy, Dinh Ha Duy; Kikuchi, Mihoko; Hien, Tran Tinh; Zamora, Javier; Hirayama, Kenji

    2013-01-01

    Background The pathogenesis of dengue shock syndrome (DSS, grade 3 and 4) is not yet completely understood. Several factors are reportedly associated with DSS, a more severe form of dengue infection that reportedly causes 50 times higher mortality compared to that of dengue patients without DSS. However, the results from these reports remain inconclusive. To better understand the epidemiology, clinical manifestation, and pathogenesis of DSS for development of new therapy, we systematically reviewed and performed a meta-analysis of relevant studies that reported factors in both DSS and dengue hemorrhagic fever (DHF, grade 1 and 2) patients. Methods and Findings PubMed, EMBASE, Scopus, Google Scholar, Dengue Bulletin, Cochrane Library, Virtual Health Library, and a manual search of reference lists of articles published before September 2010 were used to retrieve relevant studies. A meta-analysis using fixed- or random-effects models was used to calculate pooled odds ratios (OR) or event rate with corresponding 95% confidence intervals. Assessment of heterogeneity and publication bias, meta-regression analysis, subgroup analysis, sensitivity analysis, and analysis of factor-specific relationships were further performed. There were 198 studies constituting 203 data sets that met our eligibility criteria. Our meta-regression analysis showed a sustained reduction of DSS/dengue hemorrhagic fever (DHF) ratio over a period of 40 years in Southeast Asia, especially in Thailand. The meta-analysis revealed that age, female sex, neurological signs, nausea/vomiting, abdominal pain, gastrointestinal bleeding, hemoconcentration, ascites, pleural effusion, hypoalbuminemia, hypoproteinemia, hepatomegaly, levels of alanine transaminase and aspartate transaminase, thrombocytopenia, prothrombin time, activated partial thromboplastin time, fibrinogen level, primary/secondary infection, and dengue virus serotype-2 were significantly associated with DSS when pooling all original relevant

  11. Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis

    PubMed Central

    You, Ruxu; Yang, Yu; Liao, Jing; Chen, Dongsheng; Yu, Lixiu

    2016-01-01

    Background Previous studies have indicated that intake of dietary flavonoids or flavonoid subclasses is associated with the ovarian cancer risk, but presented controversial results. Therefore, we conducted a meta-analysis to derive a more precise estimation of these associations. Methods We performed a search in PubMed, Google Scholar and ISI Web of Science from their inception to April 25, 2015 to select studies on the association among dietary flavonoids, flavonoid subclasses and ovarian cancer risk. The information was extracted by two independent authors. We assessed the heterogeneity, sensitivity, publication bias and quality of the articles. A random-effects model was used to calculate the pooled risk estimates. Results Five cohort studies and seven case-control studies were included in the final meta-analysis. We observed that intake of dietary flavonoids can decrease ovarian cancer risk, which was demonstrated by pooled RR (RR = 0.82, 95% CI = 0.68–0.98). In a subgroup analysis by flavonoid subtypes, the ovarian cancer risk was also decreased for isoflavones (RR = 0.67, 95% CI = 0.50–0.92) and flavonols (RR = 0.68, 95% CI = 0.58–0.80). While there was no compelling evidence that consumption of flavones (RR = 0.86, 95% CI = 0.71–1.03) could decrease ovarian cancer risk, which revealed part sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed based on the results of Funnel plot analysis and Egger’s test (p = 0.26). Conclusions This meta-analysis suggested that consumption of dietary flavonoids and subtypes (isoflavones, flavonols) has a protective effect against ovarian cancer with a reduced risk of ovarian cancer except for flavones consumption. Nevertheless, further investigations on a larger population covering more flavonoid subclasses are warranted. PMID:26960146

  12. Human diarrhea infections associated with domestic animal husbandry: a systematic review and meta-analysis

    PubMed Central

    Zambrano, Laura D.; Levy, Karen; Menezes, Neia P.; Freeman, Matthew C.

    2014-01-01

    Domestic animal husbandry, a common practice globally, can lead to zoonotic transmission of enteric pathogens. However, this risk has received little attention to date. This systematic review and meta-analysis examines the evidence for an association between domestic exposure to food-producing animals and cases of human diarrhea and specific enteric infections. We performed a systematic review of available literature to examine domestic livestock and poultry as risk factors for diarrhea and applied pre-determined quality criteria. Where possible, we carried out meta-analysis of specific animal–pathogen pairs. We found consistent evidence of a positive association between exposure to domestic food-producing animals and diarrheal illness across a range of animal exposures and enteric pathogens. Out of 29 studies included in the review, 20 (69.0%) reported a positive association between domestic animal exposure and diarrhea. Domestic exposure to poultry revealed a substantial association with human campylobacteriosis (OR 2.73, 95% CI 1.90–3.93). Our results suggest that domestic poultry and livestock exposures are associated with diarrheal illness in humans. Failure to ascertain the microbial cause of disease may mask this effect. Exposure to domestic animals should be considered a risk factor for human diarrheal illness and additional studies may identify potential mitigation strategies to address this risk. PMID:24812065

  13. Association of Gestational Hypertensive Disorders with Retinopathy of prematurity: A Systematic Review and Meta-analysis

    PubMed Central

    Chan, Priscilla Y. L.; Tang, Shu-Min; Au, Sunny C. L.; Rong, Shi-Song; Lau, Henry H. W.; Ko, Simon T. C.; Ng, Danny S. C.; Chen, Li Jia; Yam, Jason C. S.

    2016-01-01

    The role of gestational hypertensive disorders, which includes both pre-eclampsia and gestational hypertension, in the development of retinopathy of prematurity (ROP) has been controversial. Therefore, this systematic review and meta-analysis is to evaluate the association between gestational hypertensive disoders and ROP. Eligible studies published up to June 5, 2016 were identified from MEDLINE and EMBASE that evaluated the association between the two conditions. Totally 1142 published records were retrieved for screening, 925 of them eligible for detailed evaluation. Finally 19 studies involving 45281 infants with 5388 cases of ROP met our criteria for meta-analysis. Gestational hypertensive disorders were not associated with ROP (unadjusted OR: 0.89; P = 0.38; adjusted OR: 1.35; P = 0.18). Subgroup analyses also revealed no significant association between ROP with pre-eclampsia (unadjusted OR: 0.85; P = 0.29; adjusted OR:1.29; P = 0.28) or with gestational hypertension (unadjusted OR: 1.10; P = 0.39; adjusted OR: 1.25; P = 0.60) separately. Sensitivity analysis indicated our results were robust. We concluded no significant association between gestational hypertensive disorders and ROP. More large scale well-conducted prospective cohorts on the topic are needed. PMID:27491726

  14. Association between MGMT Promoter Methylation and Non-Small Cell Lung Cancer: A Meta-Analysis

    PubMed Central

    Gu, Changmei; Lu, Jiachun; Cui, Tianpen; Lu, Cheng; Shi, Hao; Xu, Wenmao; Yuan, Xueli; Yang, Xiaobo; Huang, Yangxin; Lu, Meixia

    2013-01-01

    Background O6-methylguanine-DNA methyltransferase (MGMT) is one of most important DNA repair enzyme against common carcinogens such as alkylate and tobacco. Aberrant promoter methylation of the gene is frequently observed in non-small cell lung cancer (NSCLC). However, the importance of epigenetic inactivation of the gene in NSCLC published in the literature showed inconsistence. We quantified the association between MGMT promoter methylation and NSCLC using a meta-analysis method. Methods We systematically reviewed studies of MGMT promoter methylation and NSCLC in PubMed, EMBASE, Ovid, ISI Web of Science, Elsevier and CNKI databases and quantified the association between MGMT promoter methylation and NSCLC using meta-analysis method. Odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated to evaluate the strength of association. Potential sources of heterogeneity were assessed by subgroup analysis and meta-regression. Results A total of 18 studies from 2001 to 2011, with 1, 160 tumor tissues and 970 controls, were involved in the meta-analysis. The frequencies of MGMT promote methylation ranged from 1.5% to 70.0% (median, 26.1%) in NSCLC tissue and 0.0% to 55.0% (median, 2.4%) in non-cancerous control, respectively. The summary of OR was 4.43 (95% CI: 2.85, 6.89) in the random-effects model. With stratification by potential source of heterogeneity, the OR was 20.45 (95% CI: 5.83, 71.73) in heterogeneous control subgroup, while it was 4.16 (95% CI: 3.02, 5.72) in the autologous control subgroup. The OR was 5.31 (95% CI: 3.00, 9.41) in MSP subgroup and 3.06 (95% CI: 1.75, 5.33) in Q-MSP subgroup. Conclusion This meta-analysis identified a strong association between methylation of MGMT gene and NSCLC. Prospective studies should be required to confirm the results in the future. PMID:24086261

  15. Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis.

    PubMed

    Marconi, Arianna; Di Forti, Marta; Lewis, Cathryn M; Murray, Robin M; Vassos, Evangelos

    2016-09-01

    Cannabis use has been reported to induce long-lasting psychotic disorders and a dose-response relationship has been observed. We performed a systematic review of studies that investigate the association between the degree of cannabis consumption and psychosis and a meta-analysis to quantify the magnitude of effect. Published studies were identified through search of electronic databases, supplemented by manual searches of bibliographies. Studies were considered if they provided data on cannabis consumption prior to the onset of psychosis using a dose criterion (frequency/amount used) and reported psychosis-related outcomes. We performed random effects meta-analysis of individual data points generated with a simulation method from the summary data of the original studies. From 571 references, 18 studies fulfilled inclusion criteria for the systematic review and 10 were inserted in the meta-analysis, enrolling a total of 66 816 individuals. Higher levels of cannabis use were associated with increased risk for psychosis in all the included studies. A logistic regression model gave an OR of 3.90 (95% CI 2.84 to 5.34) for the risk of schizophrenia and other psychosis-related outcomes among the heaviest cannabis users compared to the nonusers. Current evidence shows that high levels of cannabis use increase the risk of psychotic outcomes and confirms a dose-response relationship between the level of use and the risk for psychosis. Although a causal link cannot be unequivocally established, there is sufficient evidence to justify harm reduction prevention programs. PMID:26884547

  16. A genome-wide association meta-analysis identifies new childhood obesity loci

    PubMed Central

    Bradfield, Jonathan P.; Taal, H. Rob; Timpson, Nicholas J.; Scherag, André; Lecoeur, Cecile; Warrington, Nicole M.; Hypponen, Elina; Holst, Claus; Valcarcel, Beatriz; Thiering, Elisabeth; Salem, Rany M.; Schumacher, Fredrick R.; Cousminer, Diana L.; Sleiman, Patrick M.A.; Zhao, Jianhua; Berkowitz, Robert I.; Vimaleswaran, Karani S.; Jarick, Ivonne; Pennell, Craig E.; Evans, David M.; St. Pourcain, Beate; Berry, Diane J.; Mook-Kanamori, Dennis O; Hofman, Albert; Rivadeinera, Fernando; Uitterlinden, André G.; van Duijn, Cornelia M.; van der Valk, Ralf J.P.; de Jongste, Johan C.; Postma, Dirkje S.; Boomsma, Dorret I.; Gauderman, William J.; Hassanein, Mohamed T.; Lindgren, Cecilia M.; Mägi, Reedik; Boreham, Colin A.G.; Neville, Charlotte E.; Moreno, Luis A.; Elliott, Paul; Pouta, Anneli; Hartikainen, Anna-Liisa; Li, Mingyao; Raitakari, Olli; Lehtimäki, Terho; Eriksson, Johan G.; Palotie, Aarno; Dallongeville, Jean; Das, Shikta; Deloukas, Panos; McMahon, George; Ring, Susan M.; Kemp, John P.; Buxton, Jessica L.; Blakemore, Alexandra I.F.; Bustamante, Mariona; Guxens, Mònica; Hirschhorn, Joel N.; Gillman, Matthew W.; Kreiner-Møller, Eskil; Bisgaard, Hans; Gilliland, Frank D.; Heinrich, Joachim; Wheeler, Eleanor; Barroso, Inês; O'Rahilly, Stephen; Meirhaeghe, Aline; Sørensen, Thorkild I.A.; Power, Chris; Palmer, Lyle J.; Hinney, Anke; Widen, Elisabeth; Farooqi, I. Sadaf; McCarthy, Mark I.; Froguel, Philippe; Meyre, David; Hebebrand, Johannes; Jarvelin, Marjo-Riitta; Jaddoe, Vincent W.V.; Smith, George Davey; Hakonarson, Hakon; Grant, Struan F.A.

    2012-01-01

    Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made to establish genetic influences on common early-onset obesity. We performed a North American-Australian-European collaborative meta-analysis of fourteen studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight novel signals yielding association with P < 5×10−6 in to nine independent datasets (n = 2,818 cases and 4,083 controls) we observed two loci that yielded a genome wide significant combined P-value, namely near OLFM4 on 13q14 (rs9568856; P=1.82×10−9; OR=1.22) and within HOXB5 on 17q21 (rs9299; P=3.54×10−9; OR=1.14). Both loci continued to show association when including two extreme childhood obesity cohorts (n = 2,214 cases and 2,674 controls). Finally, these two loci yielded directionally consistent associations in the GIANT meta-analysis of adult BMI1. PMID:22484627

  17. Polymorphismsof the CD24 Gene Are Associated with Risk of Multiple Sclerosis: A Meta-Analysis

    PubMed Central

    Braliou, Georgia G.; Pantavou, Katerina G.; Kontou, Panagiota I.; Bagos, Pantelis G.

    2015-01-01

    CD24 is a cell-surface protein mainly expressed in cells of the immune and central nervous system (CNS), cells that play a critical role in the development of multiple sclerosis (MS). In the current study, we investigated four polymorphisms of the CD24 gene regarding their associations with MS. To this end, univariate and multivariate meta-analysis were applied along with modifications to include data from family-trios so as to increase the robustness of the meta-analysis. We found that the polymorphism 226 C>T (Ala57Val) of the CD24 gene is associated with MS according to the recessive mode of inheritance (odds ratio = 1.75; 95% CI: 1.09, 2.81). Moreover, the 1527–1528 TG>del polymorphism is inversely associated with MS according to the dominant mode of inheritance (odds ratio = 0.57; 95% CI 0.39, 0.83). Conversely, the 1056 A>G and 1626 A>G polymorphisms were not found to be associated with MS. We conclude that the CD24 226 C>T polymorphism increases the risk of MS, while the 1527–1528 TG>del polymorphism seems to have a protective role against MS, suggesting that these two polymorphisms can be used as predictive biomarkers for MS development. PMID:26039238

  18. Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis

    PubMed Central

    Shirazi, Ayala; Stubbs, Brendon; Gomez, Lucia; Moore, Susan; Gaughran, Fiona; Flanagan, Robert J.; MacCabe, James H.; Lally, John

    2016-01-01

    Constipation is a frequently overlooked side effect of clozapine treatment that can prove fatal. We conducted a systematic review and meta-analysis to estimate the prevalence and risk factors for clozapine-associated constipation. Two authors performed a systematic search of major electronic databases from January 1990 to March 2016 for articles reporting the prevalence of constipation in adults treated with clozapine. A random effects meta-analysis was conducted. A total of 32 studies were meta-analyzed, establishing a pooled prevalence of clozapine-associated constipation of 31.2% (95% CI: 25.6–37.4) (n = 2013). People taking clozapine were significantly more likely to be constipated versus other antipsychotics (OR 3.02 (CI: 1.91–4.77), p < 0.001, n = 11 studies). Meta-regression identified two significant study-level factors associated with constipation prevalence: significantly higher (p = 0.02) rates of constipation were observed for those treated in inpatient versus outpatient or mixed settings and for those studies in which constipation was a primary or secondary outcome measure (36.9%) compared to studies in which constipation was not a specified outcome measure (24.8%, p = 0.048). Clozapine-associated constipation is common and approximately three times more likely than with other antipsychotics. Screening and preventative strategies should be established and appropriate symptomatic treatment applied when required. PMID:27271593

  19. No Association between TGFB1 Polymorphisms and Late Radiotherapy Toxicity: A Meta-Analysis

    PubMed Central

    Zhu, Mei-Ling; Wang, MengYun; Shi, Ting-Yan; Li, Qiao-Xin; Xi, Pan; Xia, Kai-Qin; Zheng, Leizhen; Wei, Qing-Yi

    2013-01-01

    Background Transforming growth factor-beta 1 (TGF-β1) protein may be multifunctional and related to the development of fibrosis, induction of apoptosis, extracellular signaling and inhibition of proliferation in response to radiation-induced DNA damage. Several studies have investigated associations between single nucleotide polymorphisms (SNPs) in the TGFB1 gene and risk of late radiation-induced injury of normal tissue, but the conclusions remain controversial. Methods We searched three electronic databases (i.e., MEDLINE, EMBASE and EBSCO) for eligible publications and performed a meta-analysis assessing the association of three commonly studied SNPs in TGFB1 (i.e., rs1800469, rs1800470 and rs1800471) with risk of late radiation-induced injury of normal tissue. Results We finally included 28 case-only studies from 16 publications on aforementioned SNPs in TGFB1. However, we did not find statistical evidence of any significant association with overall risk of late radiotherapy toxicity in the pooled analysis or in further stratified analysis by cancer type, endpoint, ethnicity and sample size. Conclusions This meta-analysis did not find statistical evidence for an association between SNPs in TGFB1 and risk of late radiation-induced injury of normal tissue, but this finding needs further confirmation by a single large study. PMID:24130819

  20. Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis.

    PubMed

    Shirazi, Ayala; Stubbs, Brendon; Gomez, Lucia; Moore, Susan; Gaughran, Fiona; Flanagan, Robert J; MacCabe, James H; Lally, John

    2016-01-01

    Constipation is a frequently overlooked side effect of clozapine treatment that can prove fatal. We conducted a systematic review and meta-analysis to estimate the prevalence and risk factors for clozapine-associated constipation. Two authors performed a systematic search of major electronic databases from January 1990 to March 2016 for articles reporting the prevalence of constipation in adults treated with clozapine. A random effects meta-analysis was conducted. A total of 32 studies were meta-analyzed, establishing a pooled prevalence of clozapine-associated constipation of 31.2% (95% CI: 25.6-37.4) (n = 2013). People taking clozapine were significantly more likely to be constipated versus other antipsychotics (OR 3.02 (CI: 1.91-4.77), p < 0.001, n = 11 studies). Meta-regression identified two significant study-level factors associated with constipation prevalence: significantly higher (p = 0.02) rates of constipation were observed for those treated in inpatient versus outpatient or mixed settings and for those studies in which constipation was a primary or secondary outcome measure (36.9%) compared to studies in which constipation was not a specified outcome measure (24.8%, p = 0.048). Clozapine-associated constipation is common and approximately three times more likely than with other antipsychotics. Screening and preventative strategies should be established and appropriate symptomatic treatment applied when required. PMID:27271593

  1. Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects

    PubMed Central

    Williams, Frances M K; Bansal, Aruna T; van Meurs, Joyce B; Bell, Jordana T; Meulenbelt, Ingrid; Suri, Pradeep; Rivadeneira, Fernando; Sambrook, Philip N; Hofman, Albert; Bierma-Zeinstra, Sita; Menni, Cristina; Kloppenburg, Margreet; Slagboom, P Eline; Hunter, David J; MacGregor, Alex J; Uitterlinden, Andre G; Spector, Tim D

    2013-01-01

    Objective Lumbar disc degeneration (LDD) is an important cause of low back pain, which is a common and costly problem. LDD is characterised by disc space narrowing and osteophyte growth at the circumference of the disc. To date, the agnostic search of the genome by genome-wide association (GWA) to identify common variants associated with LDD has not been fruitful. This study is the first GWA meta-analysis of LDD. Methods We have developed a continuous trait based on disc space narrowing and osteophytes growth which is measurable on all forms of imaging (plain radiograph, CT scan and MRI) and performed a meta-analysis of five cohorts of Northern European extraction each having GWA data imputed to HapMap V.2. Results This study of 4600 individuals identified four single nucleotide polymorphisms with p<5×10−8, the threshold set for genome-wide significance. We identified a variant in the PARK2 gene (p=2.8×10−8) associated with LDD. Differential methylation at one CpG island of the PARK2 promoter was observed in a small subset of subjects (β=8.74×10−4, p=0.006). Conclusions LDD accounts for a considerable proportion of low back pain and the pathogenesis of LDD is poorly understood. This work provides evidence of association of the PARK2 gene and suggests that methylation of the PARK2 promoter may influence degeneration of the intervertebral disc. This gene has not previously been considered a candidate in LDD and further functional work is needed on this hitherto unsuspected pathway. PMID:22993228

  2. Association between Dental Caries and Down Syndrome: A Systematic Review and Meta-Analysis

    PubMed Central

    Paiva, Saul Martins; Pordeus, Isabela Almeida

    2015-01-01

    Scientific evidence of susceptibility to dental caries in the population with Down Syndrome (DS) is limited and conflicting, making it difficult to establish firm conclusions. The aim of this systematic review and meta-analysis was to obtain scientific evidence of the possible association between dental caries and individuals with DS, compared to individuals without DS (control). An electronic search of five databases was performed, with no language or publication date restrictions. The studies were selected by two independent reviewers (Kappa = 0.83). The systematic review included 13 studies, while eight studies were included in the meta-analysis. The studies are presumably all at risk of bias given their observational character. Two of these evaluated the presence or absence of caries in permanent and deciduous teeth, and six evaluated the mean DMFT index in permanent teeth. Combined odds ratios (OR), standard difference, standard error and a 95% confidence interval (CI) were obtained. The vast majority of the studies found that individuals from control groups had more carious lesions or caries experience than those with DS. The results were statistically significant in seven studies (p<0.05). Meta-analysis of two studies revealed that individuals with DS had a lower dental caries than those in the control group (OR = 0.36; 95% CI = 0.22–0.57). In six studies, individuals with DS had a significantly lower mean DMFT index than individuals from the control group (Sd = -0.18; SE = 0.09; 95% CI = -0.35–-0.02). The quality of the studies varied and in general had a high risk of bias. Scientific evidence suggests that individuals with DS have fewer dental caries than individuals without DS. PMID:26086498

  3. Prevalence of polycystic ovary syndrome and its associated complications in Iranian women: A meta-analysis

    PubMed Central

    Jalilian, Anahita; Kiani, Faezeh; Sayehmiri, Fatemeh; Sayehmiri, Kourosh; Khodaee, Zahra; Akbari, Malihe

    2015-01-01

    Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and is the most common cause of infertility due to anovulation. There is no single criterion for the diagnosis of this syndrome. Objective: The purpose of this study was to investigate the prevalence of PCOS and its associated complications in Iranian women using meta-analysis method. Materials and Methods: Prevalence of PCOS was investigated from the SID, Goggle scholar, PubMed, Magiran, Irandoc, and Iranmedex, and weighting of each study was calculated according to sample size and prevalence of the binomial distribution. Data were analyzed using a random-effects model meta-analysis (Random effects model) and the software R and Stata Version 11.2. Results: 30 studies conducted between the years 2006 to 2011 were entered into meta-analysis. The total sample size was 19, 226 women aged between 10-45 years. The prevalence of PCOS based on National institute of child health and human disease of the U.S was, 6.8% (95 % CI: 4.11–8.5), based on Rotterdam was 19.5% (95 % CI: 2.24-8.14), and based on ultrasound was 4.41% (95% CI: 5.68-4.14). Also, the prevalence of hirsutism was estimated to be 13%, acne 26%, androgenic alopecia 9%, menstrual disorders 28%, overweight 21%, obesity 19%, and infertility 8%. Conclusion: The prevalence of PCOS in Iran is not high. However, given the risk of complications such as heart disease - cardiovascular and infertility, prevention of PCOS is important; we suggest that health officials must submit plans for the community in this respect. PMID:26644787

  4. Association between NADPH oxidase (NOX) and lung cancer: a systematic review and meta-analysis

    PubMed Central

    Han, Ming; Zhang, Tianhui; Yang, Lei; Ruan, Junzhong; Chang, Xiujun

    2016-01-01

    Background Lung cancer is a leading cause of death worldwide. Considerable studies have reported that NADPH oxidase (NOX) expression or activity may play an important role in the tumorigenesis of lung cancer. However, the results are inconsistent. Thus, a systematic review and meta-analysis were conducted in this study. Methods A systematic search of electronic databases was performed. Statistical analysis was performed using the Comprehensive Meta-Analysis software (Version 3). The pooled Hedges’s g with 95% confidence intervals (95% CIs) or rate ratio with 95% CIs was adopted to assess the effect size. Fixed or random effect model was separately used based on the heterogeneity between the studies. Results A total of ten eligible studies were included in the current systematic review and overall meta-analysis showed that NOX/DUOX activity and mRNA were significantly in favor of lung cancer (Hedges’s g =1.216, P=0.034). Suppression of NOX function by pharmacologic inhibitor or expression by siRNA resulted in significant inhibition of lung cancer cell invasion and migration in in vitro experiments (Hedges’s g =2.422, P<0.001) and lung cancer formation in vivo studies (rate ratio =0.366, P=0.002). Conclusions Findings of this systematic review indicate that NOX activity and expression is associated with tumorigenesis of lung cancer and inhibition of NOX function or mRNA expression significantly blocks lung cancer formation and invasion. Suppressing NOX up-regulation or interfering NOX function in tumor microenvironment may be one important approach to prevent oxidative-stress-related carcinogenesis in the lung. PMID:27499960

  5. Association between Dental Caries and Down Syndrome: A Systematic Review and Meta-Analysis.

    PubMed

    Deps, Tahyna Duda; Angelo, Gabriela Lopes; Martins, Carolina Castro; Paiva, Saul Martins; Pordeus, Isabela Almeida; Borges-Oliveira, Ana Cristina

    2015-01-01

    Scientific evidence of susceptibility to dental caries in the population with Down Syndrome (DS) is limited and conflicting, making it difficult to establish firm conclusions. The aim of this systematic review and meta-analysis was to obtain scientific evidence of the possible association between dental caries and individuals with DS, compared to individuals without DS (control). An electronic search of five databases was performed, with no language or publication date restrictions. The studies were selected by two independent reviewers (Kappa = 0.83). The systematic review included 13 studies, while eight studies were included in the meta-analysis. The studies are presumably all at risk of bias given their observational character. Two of these evaluated the presence or absence of caries in permanent and deciduous teeth, and six evaluated the mean DMFT index in permanent teeth. Combined odds ratios (OR), standard difference, standard error and a 95% confidence interval (CI) were obtained. The vast majority of the studies found that individuals from control groups had more carious lesions or caries experience than those with DS. The results were statistically significant in seven studies (p<0.05). Meta-analysis of two studies revealed that individuals with DS had a lower dental caries than those in the control group (OR = 0.36; 95% CI = 0.22-0.57). In six studies, individuals with DS had a significantly lower mean DMFT index than individuals from the control group (Sd = -0.18; SE = 0.09; 95% CI = -0.35--0.02). The quality of the studies varied and in general had a high risk of bias. Scientific evidence suggests that individuals with DS have fewer dental caries than individuals without DS. PMID:26086498

  6. A Systematic Review and Meta-analysis of the Association Between Giardia lamblia and Endemic Pediatric Diarrhea in Developing Countries

    PubMed Central

    Muhsen, Khitam; Levine, Myron M.

    2012-01-01

    We performed a systematic literature review and meta-analysis examining the association between diarrhea in young children in nonindustrialized settings and Giardia lamblia infection. Eligible were case/control and longitudinal studies that defined the outcome as acute or persistent (>14 days) diarrhea, adjusted for confounders and lasting for at least 1 year. Data on G. lamblia detection (mainly in stools) from diarrhea patients and controls without diarrhea were abstracted. Random effects model meta-analysis obtained pooled odds ratios (ORs) and 95% confidence intervals (CIs). Twelve nonindustrialized-setting acute pediatric diarrhea studies met the meta-analysis inclusion criteria. Random-effects model meta-analysis of combined results (9774 acute diarrhea cases and 8766 controls) yielded a pooled OR of 0.60 (95% CI, .38–.94; P = .03), indicating that G. lamblia was not associated with acute diarrhea. However, limited data suggest that initial Giardia infections in early infancy may be positively associated with diarrhea. Meta-analysis of 5 persistent diarrhea studies showed a pooled OR of 3.18 (95% CI, 1.50–6.76; P < .001), positively linking Giardia with that syndrome. The well-powered Global Enteric Multicenter Study (GEMS) is prospectively addressing the association between G. lamblia infection and diarrhea in children in developing countries. PMID:23169940

  7. Association Between Isolated Single Umbilical Artery and Perinatal Outcomes: A Meta-Analysis

    PubMed Central

    Xu, Yajuan; Ren, Lidan; Zhai, Shanshan; Luo, Xiaohua; Hong, Teng; Liu, Rui; Ran, Limin; Zhang, Yingying

    2016-01-01

    Background To evaluate the association between the isolated single umbilical artery (iSUA) and perinatal outcomes, including pregnancy outcomes and perinatal complications. Material/Methods We performed a meta-analysis of 15 eligible studies regarding the relationship between the iSUA and perinatal outcomes, including gestational age at delivery, nuchal cord, placental weight, small for gestational age (SGA), oligohydramnios, polyhydramnios, pregnancy-induced hypertension (PIH), gestational diabetes mellitus (GDM), preeclampsia, and perinatal mortality. The overall odds ratios (OR) or standardized mean difference (SMD) were calculated. Results The occurrence of nuchal cord was not found to be different between an iSUA and a three-vessel cord (TVC) fetus. For perinatal complications, the SGA, oligohydramnios, polyhydramnios, GDM, and perinatal mortality showed dramatic difference between women with an iSUA and women with a TVC fetus, which implied that the presence of iSUA significantly increased the risk of perinatal complications. For other perinatal complications, such as PIH and preeclampsia, no significant association was detected. Conclusions Our meta-analysis suggests that the presence of iSUA would increase the risk of perinatal complications such as SGA, oligohydramnios, polyhydramnios, GDM, and perinatal mortality. Therefore, pregnant women with an iSUA fetus have poorer perinatal outcomes and more attention should be given to the management of their pregnancy compared to women with a TVC fetus. PMID:27130891

  8. Association Between Isolated Single Umbilical Artery and Perinatal Outcomes: A Meta-Analysis.

    PubMed

    Xu, Yajuan; Ren, Lidan; Zhai, Shanshan; Luo, Xiaohua; Hong, Teng; Liu, Rui; Ran, Limin; Zhang, Yingying

    2016-01-01

    BACKGROUND To evaluate the association between the isolated single umbilical artery (iSUA) and perinatal outcomes, including pregnancy outcomes and perinatal complications. MATERIAL AND METHODS We performed a meta-analysis of 15 eligible studies regarding the relationship between the iSUA and perinatal outcomes, including gestational age at delivery, nuchal cord, placental weight, small for gestational age (SGA), oligohydramnios, polyhydramnios, pregnancy-induced hypertension (PIH), gestational diabetes mellitus (GDM), preeclampsia, and perinatal mortality. The overall odds ratios (OR) or standardized mean difference (SMD) were calculated. RESULTS The occurrence of nuchal cord was not found to be different between an iSUA and a three-vessel cord (TVC) fetus. For perinatal complications, the SGA, oligohydramnios, polyhydramnios, GDM, and perinatal mortality showed dramatic difference between women with an iSUA and women with a TVC fetus, which implied that the presence of iSUA significantly increased the risk of perinatal complications. For other perinatal complications, such as PIH and preeclampsia, no significant association was detected. CONCLUSIONS Our meta-analysis suggests that the presence of iSUA would increase the risk of perinatal complications such as SGA, oligohydramnios, polyhydramnios, GDM, and perinatal mortality. Therefore, pregnant women with an iSUA fetus have poorer perinatal outcomes and more attention should be given to the management of their pregnancy compared to women with a TVC fetus. PMID:27130891

  9. A Meta-Analysis for Association of Maternal Smoking with Childhood Refractive Error and Amblyopia

    PubMed Central

    Li, Li; Qi, Ya; Shi, Wei; Wang, Yuan; Liu, Wen; Hu, Man

    2016-01-01

    Background. We aimed to evaluate the association between maternal smoking and the occurrence of childhood refractive error and amblyopia. Methods. Relevant articles were identified from PubMed and EMBASE up to May 2015. Combined odds ratio (OR) corresponding with its 95% confidence interval (CI) was calculated to evaluate the influence of maternal smoking on childhood refractive error and amblyopia. The heterogeneity was evaluated with the Chi-square-based Q statistic and the I2 test. Potential publication bias was finally examined by Egger's test. Results. A total of 9 articles were included in this meta-analysis. The pooled OR showed that there was no significant association between maternal smoking and childhood refractive error. However, children whose mother smoked during pregnancy were 1.47 (95% CI: 1.12–1.93) times and 1.43 (95% CI: 1.23-1.66) times more likely to suffer from amblyopia and hyperopia, respectively, compared with children whose mother did not smoke, and the difference was significant. Significant heterogeneity was only found among studies involving the influence of maternal smoking on children's refractive error (P < 0.05; I2 = 69.9%). No potential publication bias was detected by Egger's test. Conclusion. The meta-analysis suggests that maternal smoking is a risk factor for childhood hyperopia and amblyopia. PMID:27247800

  10. Meta-analysis in psychiatric genetics.

    PubMed

    Levinson, Douglas F

    2005-04-01

    The article reviews literature on methods for meta-analysis of genetic linkage and association studies, and summarizes and comments on specific meta-analysis findings for psychiatric disorders. The Genome Scan Meta-Analysis and Multiple Scan Probability methods assess the evidence for linkage across studies. Multiple Scan Probability analysis suggested linkage of two chromosomal regions (13q and 22q) to schizophrenia and bipolar disorder, whereas Genome Scan Meta-Analysis on a larger sample identified at least 10 schizophrenia linkage regions, but none for bipolar disorder. Meta-analyses of pooled ORs support association of schizophrenia to the Ser311Cys polymorphism in DRD2 and the T102C polymorphism in HTR2A, and of attention deficit hyperactivity disorder to the 48-bp repeat in DRD4. The 5-HTTLPR polymorphism in the serotonin transporter gene (SLC6A4) may contribute to the risk of bipolar disorder, suicidal behavior, and neuroticism, but association to the lifetime risk of major depression has not been shown. Meta-analyses support linkage of schizophrenia to regions where replicable associations to candidate genes have been identified through positional cloning methods. There are additional supported regions where susceptibility genes are likely to be identified. Linkage meta-analysis has had less clear success for bipolar disorder based on a smaller dataset. Meta-analysis can guide the prioritization of regions for study, but proof of association requires biological confirmation of hypotheses about gene actions. Elucidation of causal mechanisms will require more comprehensive study of sequence variation in candidate genes, better statistical and meta-analytic methods to take all variation into account, and biological strategies for testing etiologic hypotheses. PMID:15802092

  11. Meat subtypes and their association with colorectal cancer: Systematic review and meta-analysis.

    PubMed

    Carr, Prudence R; Walter, Viola; Brenner, Hermann; Hoffmeister, Michael

    2016-01-15

    Associations between specific red meat subtypes and risk of colorectal cancer (CRC) have been investigated in a number of epidemiological studies. However, no publication to date has summarised the overall epidemiological evidence. We conducted a systematic review and meta-analysis of prospective studies (cohort, nested case-control or case-cohort studies), which reported relative risk (RR) estimates and 95% confidence intervals (CI) for the association between intake of meat subtypes with colorectal, colon or rectal cancer or colorectal adenoma risk. PubMed and ISI Web of Science were searched up until August 1, 2014. Nineteen studies examined meat subtypes (5 beef, 5 pork, 2 lamb, 1 veal and 19 poultry) and associations with colorectal, colon or rectal cancer risk and 4 studies examined associations with adenoma risk (1 beef and 4 poultry). Comparing highest versus lowest intake, beef consumption was associated with an increased risk of CRC (RR = 1.11, 95% CI = 1.01 to 1.22) and colon cancer (RR = 1.24, 95% CI = 1.07 to 1.44), but no association was found with rectal cancer (RR = 0.95, 95% CI = 0.78 to 1.16). Higher consumption of lamb was also associated with increased risk of CRC (RR = 1.24, 95% CI = 1.08 to 1.44). No association was observed for pork (RR = 1.07, 95% CI = 0.90 to 1.27), but some between study heterogeneity was observed. No association was observed for poultry consumption and risk of colorectal adenomas or cancer. This meta-analysis suggests that red meat subtypes differ in their association with CRC and its sub sites. Further analysis of data from prospective cohort studies is warranted, especially regarding the role of pork. PMID:25583132

  12. Association between Liver Fluke Infection and Hepatobiliary Pathological Changes: A Systematic Review and Meta-Analysis

    PubMed Central

    Xia, Jing; Jiang, Shi-chen; Peng, Hong-Juan

    2015-01-01

    Objective To provide information about the role of liver fluke infection as a risk factor for hepatobiliary pathological changes and promote awareness among the people living in endemic areas, a systematic review and meta-analysis based on published studies was conducted to examine the association between liver fluke infection and hepatobiliary pathological changes. Methods Relevant original literature was searched in multiple literature databases, including PubMed, Cochrane, Clinical Evidence, Trip Database, Clinical Trials, Current Controlled Trials, Web of Science, the China National Knowledge Infrastructure (CNKI) database, and the Wanfang academic journal full-text database. Studies were selected based on strict screening with inclusion and exclusion criteria. Tests of heterogeneity, sensitivity and publication bias were performed with the Review Manager software, version 5.3, and meta-regression analyses were performed with the Stata software, version 11.0 (Stata Corporation, College Station, TX, USA). Pooled risk ratios (RRs) and odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated and used to evaluate the risk of hepatobiliary pathological changes resulting from liver fluke infection. Linear trend analyses were conducted to determine the dose-response relationship using IBM SPSS Statistics 20.0. Result A total of 36 studies were included in the meta-analysis. Significant associations were found between liver fluke infection and cholangitis or cholecystitis (RR: 7.80, P<0.001; OR: 15.98, P<0.001), cholelithiasis (RR: 2.42, P = 0.03; OR: 4.96, P = 0.03), hepatocellular carcinoma (OR: 4.69, P<0.001) and cholangiocarcinoma (RR: 10.43, P<0.001; OR: 4.37, P<0.001). In addition, heavier infection was significantly associated with higher incidence of hepatobiliary pathological changes (P<0.05). However, cirrhosis was not significantly associated with liver fluke infection (RR: 3.50, P = 0.06; OR: 5.79, P = 0.08). The statistical

  13. The association between BMI and cervical cancer risk: a meta-analysis.

    PubMed

    Poorolajal, Jalal; Jenabi, Ensiyeh

    2016-05-01

    The association between BMI and cervical cancer risk is not clear. This meta-analysis was carried out to estimate the association between overweight and obesity and cervical cancer risk. We searched PubMed, Web of Science, Scopus, ScienceDirect, LILACS, and SciELO for observational studies addressing the association between BMI and cervical cancer until February 2015. Data were independently extracted and analyzed using odds ratios and 95% confidence intervals (CIs), on the basis of random-effects models. We identified a total of 3543 references and included nine studies with 128 233 participants. On the basis of the results of case-control and cohort studies, the association between cervical cancer and overweight was estimated to be 1.03 (95% CI: 0.81, 1.25) and 1.10 (95% CI: 1.03, 1.17), respectively. According to the results of case-control and cohort studies, the association between cervical cancer and obesity was estimated to be 1.40 (95% CI: 1.08, 1.71) and 1.08 (95% CI: 0.60, 1.52), respectively. No evidence of heterogeneity and publication bias was observed. The findings from this meta-analysis indicate that overweight is not associated with an increased risk of cervical cancer, but obesity is weakly associated with an increased risk of cervical cancer. However, more evidence, based on large prospective cohort studies, is required to provide conclusive evidence on whether or not BMI is associated with an increased risk of cervical cancer. PMID:25932869

  14. Meta-analysis of associations between MTHFR and GST polymorphisms and susceptibility to multiple sclerosis.

    PubMed

    Lee, Young Ho; Seo, Young Ho; Kim, Jae-Hoon; Choi, Sung Jae; Ji, Jong Dae; Song, Gwan Gyu

    2015-11-01

    We examined whether methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST) polymorphisms are associated with susceptibility to multiple sclerosis (MS). We performed a meta-analysis on the association between MS and the following genotypes: MTHFR C677T, A1298C, and GSTP1 A313G polymorphisms, and GSTM1 and GSTT1 null alleles. Fifteen comparisons involving 2,486 patients and 2,861 controls were considered. Meta-analysis of all study subjects considered together showed no association between MS and the MTHFR 677 T allele (OR = 1.014, 95 % CI 0.803-1.280, p = 0.909). Stratification by ethnicity showed no similar association in Caucasian and Arab populations. Likewise, no link was found between MS and the MTHFR 1298 C allele in the total data (OR = 2.477, 95 % CI 0.507-12.10, p = 0.263), nor when it was stratified by ethnicity. No association with MS was observed in relation to the GSTM1 null genotype in Caucasian populations (OR = 1.229, 95 % CI 0.693-2.181, p = 0.481), nor with the GSTP1 A313G polymorphism (OR for G allele = 1.133, 95 % CI 0.903-1.421, p = 0.281). However, there was an association between MS and the GSTT1 null genotype in data obtained from Caucasian populations (OR = 1.945, 95 % CI 1.452-2.605, p = 8.6 × 10(-7)). GSTT1 null genotype is associated with MS in Caucasian populations; however, no association was found between MS and polymorphisms of MTHFR, GSTM1, and GSTP1. PMID:26150166

  15. Association between TNFA Gene Polymorphisms and Helicobacter pylori Infection: A Meta-Analysis

    PubMed Central

    Sun, Xudong; Xu, Yuanyuan; Wang, Li; Zhang, Fuhua; Zhang, Jinhua; Fu, Ximei; Jing, Tao; Han, Jian

    2016-01-01

    Background Several host genetic factors are thought to affect susceptibility to Helicobacter pylori infection-related diseases, including tumor necrosis factor (TNF)-α. Previous studies have evaluated the association between TNFA gene polymorphisms and H. pylori infection, but the results were inconclusive. We conducted this meta-analysis to clarify the association between TNFA polymorphisms and H. pylori infection. Methods Published literature within PubMed, Embase, and the Cochrane Library were used in our meta-analysis. Data were analyzed with the Stata13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (CI). Results A total of 24 studies were included in our study. The TNFA -308G>A polymorphism was associated with decreasing H. pylori infection (AA vs. AG+GG, OR = 0.64, 95% CI = 0.43–0.97; AA vs. GG, OR = 0.64, 95% CI = 0.43–0.97). A significantly decreased risk was also found for -1031T>C polymorphism (CC vs. CT+TT, OR = 0.61, 95% CI = 0.44–0.84). -863C>A polymorphism was associated with increasing risk of H. pylori infection (AA+AC vs. CC, OR = 1.47, 95% CI = 1.16–1.86; A allele vs. C allele, OR = 1.40, 95% CI = 1.14–1.72). There was no significant association between -857C>T polymorphism and H. pylori infection. When stratified analysis was conducted on H. pylori infection detection methods, -857C>T and -863C>A polymorphisms were associated with H. pylori infection for the non-ELISA subgroup. When stratified for ethnicity or study design, -863C>A significantly increased the risk and -1031T>C decreased the risk for the Asian subgroup and hospital-based subgroup. Conclusion Results of our meta-analysis demonstrate that TNFA -308G>A and -1031 T>C polymorphisms may be protective factors against H. pylori infection, and -863C>A may be a risk factor, especially in Asian populations. Further studies with larger sample sizes are required to validate these results. PMID:26815578

  16. Association between Occupational Exposure to Wood Dust and Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Alonso-Sardón, Montserrat; Chamorro, Antonio-J.; Hernández-García, Ignacio; Iglesias-de-Sena, Helena; Martín-Rodero, Helena; Herrera, Cristian; Marcos, Miguel; Mirón-Canelo, José Antonio

    2015-01-01

    Objective To perform a systematic review to analyze the association between occupational exposure to wood dust and cancer. Methods A systematic literature search of entries made in the MEDLINE-PubMed database between 1957 and 2013 was conducted to identify studies that had assessed the relationship between occupational exposure to wood dust and different types of cancer. A meta-analysis of selected case-control and cohort studies was subsequently performed. Results A total of 114 studies were identified and 70 were selected for review. Of these, 42 studies focused on the relationship between wood dust and nasal cancer (n = 22), lung cancer (n = 11), and other types of cancer (n = 9). Low-to-moderate quality evidence that wood dust acts as a carcinogen was obtained, and a stronger association between wood dust and nasal adenocarcinoma was observed. A lesser association between wood dust exposure and lung cancer was also observed. Several studies suggested that there is a relationship between wood dust and the onset of other cancers, although there was no evidence to establish an association. A meta-analysis that included four case-controls studies showed that workers exposed to wood dust exhibited higher rates of nasal adenocarcinoma than other workers (odds ratio = 10.28; 95% confidence interval: 5.92 and 17.85; P<0,0001), although a large degree of heterogeneity was found. Conclusions Low-to-moderate quality evidence supports a causal association between cancer and occupational exposure to wood dust, and this association was stronger for nasal adenocarcinoma than for lung cancer. There was no evidence of an association between wood dust exposure and the other cancers examined. PMID:26191795

  17. The Association between Metabolic Syndrome and Colorectal Neoplasm: Systemic review and Meta-analysis

    PubMed Central

    Jinjuvadia, Raxitkumar; Lohia, Prateek; Jinjuvadia, Chetna; Montoya, Sergio; Liangpunsakul, Suthat

    2012-01-01

    Background There has been constant speculation about the association between metabolic syndrome (MetS) and colorectal neoplasia (CN); however, the published results are conflicting. The aims of this study are to systematic search, and assess literature to determine the available evidence on the association between these two conditions. Methods Meta-analysis was conducted based on relevant studies identified through a systematic literature review from PubMed, OvidSP and Cochrane database during January 1980 to July 2011. A combined analysis was performed, followed by a subgroup analyses stratified by the study design, type of colorectal lesions and gender. Publication bias was assessed using the Begg’s and Egger’s tests and visual inspection of funnel plot. Results Eighteen studies were included in the final analysis. Overall, MetS was associated with 34% increase in the risk of CN (summary RR - 1.34, 95% CI 1.24–1.44). The association between MetS and CN was found to be statistically significant in separate analysis for both case-control studies (summary RR -1.58, 95% CI 1.44–1.79) and cohort studies (summary RR – 1.21, 95% CI 1.13–1.29). The association remained significant when analyses were restricted by type of colorectal lesions (colorectal cancer: RR – 1.30, 95% CI 1.18–1.43; colorectal adenoma: RR – 1.37, 95% CI 1.26–1.49). Further subgroup analysis by gender showed significant association between MetS and CN in both male and female population. Conclusion Our meta-analysis showed significant association between presence of MetS and CN. These results may help in identifying high risk individuals at early stage that might benefit from targeted CRC screening intervention. PMID:23090040

  18. Increased mortality for pregnancy-associated melanoma: systematic review and meta-analysis.

    PubMed

    Byrom, L; Olsen, C; Knight, L; Khosrotehrani, K; Green, A C

    2015-08-01

    Among women, pregnancy-associated melanomas may have a poorer prognosis than other melanomas, but evidence is inconsistent. We conducted a systematic review and meta-analysis to assess the effect on melanoma outcome of a coinciding pregnancy. The objective of the study was to conduct a systematic review and meta-analysis of risk of death from, or recurrence of, pregnancy-associated melanomas compared with other melanomas in women of reproductive age. Cochrane (1996-2013), MEDLINE (1950-2013), EMBASE (1966-2013), CINAHL (1982-2013), and PUBMED (1951-2013) databases were searched for studies assessing the risk of death and recurrence in pregnancy-associated melanomas. Eligible studies investigated melanoma outcomes in women with pregnancy-associated melanomas (diagnosed during pregnancy or in 12 months following pregnancy), included a comparison group and reported measures of risk of melanoma death or disease-free survival. Eligible study designs were cohort studies of women of childbearing age with confirmed diagnoses of cutaneous melanoma. Individual study effect estimates were pooled using the weighted average method. Studies that did not report a quantitative estimate were summarized narratively. Of 304 citations identified, 14 studies met the inclusion criteria, with assessed outcomes being melanoma death (7), recurrence (3), or both (4). Pooled estimates of mortality risk from four studies showed increased risk of melanoma death after adjustment for patient age and stage of melanoma (pHR 1.56, 95% CI 1.23-1.99) for pregnancy-associated melanoma compared with other melanomas. Based on limited quantitative evidence, pregnancy-associated melanomas appear to have poorer outcomes than other melanomas. PMID:25690106

  19. Association between Glaucoma and Obstructive Sleep Apnea Syndrome: A Meta-Analysis and Systematic Review

    PubMed Central

    Shi, Yuhua; Liu, Panpan; Guan, Jian; Lu, Yan; Su, Kaiming

    2015-01-01

    Background Obstructive sleep apnea syndrome (OSAS) is a common disease that increases the risk of diabetes, heart disease, and stroke. However, studies of an association between OSAS and glaucoma neuropathy have reported controversial findings. Objective The main purpose of this study was to evaluate whether a significant association exists between OSAS and glaucoma by performing a meta-analysis of previous studies. Methods A comprehensive literature search using the PubMed and Embase databases was performed to identify cross-sectional, case-control, and cohort studies related to the topic. We estimated a pooled odds ratio (OR) for the association between OSAS and glaucoma, by a fixed- or random-effects model. Results In total, 16 studies with 2,278,832 participants met the inclusion criteria: one retrospective cohort study reported an adjusted hazard ratio of glaucoma of 1.67 (95% CI = 1.30–2.17). Using a fixed-effects model, the pooled OR of six case-control studies was 1.96 (95% CI = 1.37 2.80). A significant association was also identified in a meta-analysis of nine cross-sectional studies using a random-effects model, which showed a pooled OR of 1.41 (95% CI = 1.11 1.79). However, the reported pooled estimates for case control studies and cross-sectional studies were based on unadjusted ORs. Conclusions Our results suggest that OSAS is associated with the prevalence of glaucoma. However, this result was based only on unadjusted estimates. Prospective cohort studies designed to take into consideration potential confounders, or examination of data from interventional trials to determine whether a reduction in OSAS status is associated with a reduced incidence of glaucoma, are needed to clarify whether OSAS is an independent risk factor for glaucoma. PMID:25705901

  20. Is hypertension associated with job strain? A meta-analysis of observational studies.

    PubMed

    Babu, Giridhara R; Jotheeswaran, A T; Mahapatra, Tanmay; Mahapatra, Sanchita; Kumar, Ananth; Detels, Roger; Pearce, Neil

    2014-03-01

    Job strain results from a combination of high workload and few decision-making opportunities in the workplace. There is inconsistent evidence regarding the association between job strain and hypertension, and methodological shortcomings preclude firm conclusions. Thus, a meta-analysis of observational studies on hypertension among occupational groups was conducted to determine whether job strain was associated with hypertension. In January 2012, we carried out a comprehensive, topic-specific electronic literature search of the Ovid MEDLINE, EMBASE and PsychoINFO databases complemented by individual help from non-communicable disease experts. Experimental/interventional studies and studies on personality disorders were excluded. Nine of 894 identified studies met the eligibility criteria and were included in the meta-analysis. The pooled OR of the nine studies was 1.29 (95% CI 1.14 to 1.47; p<0.001), of case–control studies 2.88 (95% CI 1.63 to 5.09; p<0.001) and of cohort studies 1.24 (95% CI1.09 to 1.41; p<0.001), all of which indicated statistically significant positive associations between job strain and hypertension [corrected]. In a subgroup analysis, cohort studies of good methodological quality showed significant associations between job strain and hypertension, while those of poor methodological quality showed no association or subgroup differences. We conclude that despite methodological differences, case-control and cohort studies of good methodological quality showed positive associations between hypertension and job strain. PMID:24142979

  1. Association of COL1A1 polymorphisms with osteoporosis: a meta-analysis of clinical studies

    PubMed Central

    Xie, Peigen; Liu, Bin; Zhang, Liangming; Chen, Ruiqiang; Yang, Bu; Dong, Jianwen; Rong, Limin

    2015-01-01

    Objective: To conduct a meta-analysis of all association studies on two of the collagen 1 alpha 1 (COL1A1) gene polymorphisms, the -1997G/T (rs1107946) and the -1663indelT (rs2412298) polymorphisms and osteoporosis/BMD and fracture. Methods: PubMed/Medline and Web of Knowledge were searched for relevant association studies published in English. Pooled OR and its corresponding 95% CI or pooled MD and its corresponding 95% CI was calculated with the Cochrane Review Manager (Revman, version 5.2) using a random-effect or a fixed effect model. Results: No significant association between the -1997G/T polymorphism and Lumbar Spine (LS) and Femoral Neck (FN) BMD except for the Caucasian subpopulation wherein subjects with the T allele of the -1997G/T polymorphism was associated with significantly higher LS BMD. Our analysis did reveal that women, especially postmenopausal or perimenopausal women with the GG genotype, had significantly higher Total Hip (TH) BMD than those with the GT. Additionally, our meta-analysis did not show significant association between the -1997G/T polymorphism and risk of fracture, between the -1663indelT polymorphism and LS BMD in postmenopausal or perimenopausal women, or between the -1663indelT polymorphism and the risk of fracture. Conclusions: Our results suggested the possibility of the COL1A1 -1997G/T and the -1663indelT polymorphisms individually playing very little role in osteoporosis and fracture, although more studies are needed especially for the analysis of association between these two polymorphisms and fracture. Haplotype studies may become one important future direction of study to further elucidate whether and how various COL1A1 polymorphisms affect bone health, osteoporosis and fracture. PMID:26628959

  2. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

    PubMed Central

    Evangelou, Evangelos; Kerkhof, Hanneke J; Styrkarsdottir, Unnur; Ntzani, Evangelia E; Bos, Steffan D; Esko, Tonu; Evans, Daniel S; Metrustry, Sarah; Panoutsopoulou, Kalliope; Ramos, Yolande F M; Thorleifsson, Gudmar; Tsilidis, Konstantinos K; Arden, Nigel; Aslam, Nadim; Bellamy, Nicholas; Birrell, Fraser; Blanco, Francisco J; Carr, Andrew; Chapman, Kay; Day-Williams, Aaron G; Deloukas, Panos; Doherty, Michael; Engström, Gunnar; Helgadottir, Hafdis T; Hofman, Albert; Ingvarsson, Thorvaldur; Jonsson, Helgi; Keis, Aime; Keurentjes, J Christiaan; Kloppenburg, Margreet; Lind, Penelope A; McCaskie, Andrew; Martin, Nicholas G; Milani, Lili; Montgomery, Grant W; Nelissen, Rob G H H; Nevitt, Michael C; Nilsson, Peter M; Ollier, William ER; Parimi, Neeta; Rai, Ashok; Ralston, Stuart H; Reed, Mike R; Riancho, Jose A; Rivadeneira, Fernando; Rodriguez-Fontenla, Cristina; Southam, Lorraine; Thorsteinsdottir, Unnur; Tsezou, Aspasia; Wallis, Gillian A; Wilkinson, J Mark; Gonzalez, Antonio; Lane, Nancy E; Lohmander, L Stefan; Loughlin, John; Metspalu, Andres; Uitterlinden, Andre G; Jonsdottir, Ingileif; Stefansson, Kari; Slagboom, P Eline; Zeggini, Eleftheria; Meulenbelt, Ingrid; Ioannidis, John PA; Spector, Tim D; van Meurs, Joyce B J; Valdes, Ana M

    2014-01-01

    Objectives Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for ‘in silico’ or ‘de novo’ replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. Results We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10−9 and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10−8) and follow-up studies (p=7.3×10−4). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10−7, OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10−6, OR=1.27 in male specific analysis). Conclusions Novel genetic loci for hip OA were found in this meta-analysis of GWAS. PMID:23989986

  3. Association between selenium levels and oesophageal adenocarcinoma risk: evidence from a meta-analysis

    PubMed Central

    Hong, Bin; Huang, Lihong; Mao, Ning; Xiong, Tao; Li, Chao

    2016-01-01

    Quantification of the association between selenium and risk of oesophageal adenocarcinoma (OAC) is still conflicting. The purpose of this meta-analysis is to explore the relationship between selenium levels and OAC risk. PubMed and Web of Knowledge were searched for the related articles. Pooled relative risks (RRs) with 95% confidence intervals (CIs) from random effects models were calculated. Sensitivity analysis and publication bias were conducted. Dose–response relationship was assessed by restricted cubic spline and variance-weighted least squares regression analysis. Five articles involving 748 OAC cases were included in this meta-analysis. Pooled results suggest that higher selenium level was not significantly associated with the risk of OAC (summary RRs=1.08, 95% CIs=0.84–1.39, I2=0%). Besides, no significant association was found in case-control studies (summary RRs=1.13, 95% CIs=0.84–1.52, I2=0%) or cohort studies (summary RRs=0.99, 95% CIs=0.55–1.78, I2=32.6%). A linear dose–response relationship was attested that an increase in dietary selenium intake of 10 μg/day is marginally associated with 1% increase in the risk of developing OAC (summary RRs=1.01, 95% CIs=0.99–1.03), but not statistically significant. No publication bias was found. In conclusion, our analysis indicated that a higher selenium level was not significantly associated with the risk of OAC. The relevant further studies are warranted. PMID:27190131

  4. Association between caffeine consumption and nonalcoholic fatty liver disease: a systemic review and meta-analysis

    PubMed Central

    Shen, Huafeng; Rodriguez, Andrea C.; Shiani, Ashok; Lipka, Seth; Shahzad, Ghulamullah; Kumar, Ambuj; Mustacchia, Paul

    2016-01-01

    Objectives: Caffeine consumption is reported to be associated with reduced hepatic fibrosis in patients with chronic liver diseases. We performed a systematic review and meta-analysis to assess the association between caffeine consumption and prevalence or hepatic fibrosis of nonalcoholic fatty liver disease (NAFLD) in observational studies. Methods: We searched the literature of all languages from PubMed, EMBASE, and the Cochrane library from 1 January 1980 through 10 January 2015. Total caffeine consumption was defined as the daily intake of caffeine (mg/day) from all caffeine-containing products. Combined and subgroup analyses stratified by study designs, study locations, and type of caffeine intake were performed. Results: Four cross-sectional and two case control studies with a total of 20,064 subjects were included in the meta-analysis. Among these, three studies with 18,990 subjects were included in the analysis for prevalence of NAFLD while the other three studies with 1074 subjects were for hepatic fibrosis. Total caffeine consumption (mg/day) was not significantly associated with either the prevalence [pooled mean difference (MD) 2.36; 95% confidence interval (CI) −35.92 to 40.64] or hepatic fibrosis (higher versus lower stages; pooled MD −39.95; 95% CI −132.72 to 52.82) of NAFLD. Subgroup analyses stratified by study designs and locations were also not significant. However, after stratifying by type of caffeine intake, regular coffee caffeine intake (mg/day) was significantly associated with reduced hepatic fibrosis of NAFLD (pooled MD −91.35; 95% CI −139.42 to −43.27; n = 2 studies). Conclusion: Although total caffeine intake is not associated with the prevalence or hepatic fibrosis of NAFLD, regular coffee caffeine consumption may significantly reduce hepatic fibrosis in patients with NAFLD. PMID:26770272

  5. Human Endogenous Retrovirus HERV-Fc1 Association with Multiple Sclerosis Susceptibility: A Meta-Analysis

    PubMed Central

    García-Montojo, Marta; Alcina, Antonio; Fedetz, María; Alloza, Iraide; Astobiza, Ianire; Leyva, Laura; Fernández, Oscar; Izquierdo, Guillermo; Antigüedad, Alfredo; Arroyo, Rafael; Álvarez-Lafuente, Roberto; Vandenbroeck, Koen; Matesanz, Fuencisla; Urcelay, Elena

    2014-01-01

    Background Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. Methods A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data. Results Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: pM-H = 0.0005; ORM-H (95% CI) = 1.27 (1.11–1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [pM-H = 0.0003, ORM-H (95% CI) = 1.32 (1.14–1.53)]. Conclusion Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts. PMID:24594754

  6. Association between three exonuclease 1 polymorphisms and cancer risks: a meta-analysis

    PubMed Central

    Chen, Zi-Yu; Zheng, Si-Rong; Zhong, Jie-Hui; Zhuang, Xiao-Duan; Zhou, Jue-Yu

    2016-01-01

    To date, the results of studies exploring the relation between exonuclease 1 (Exo1) polymorphisms and cancer risks have differed. In this study, we performed a meta-analysis to investigate the effect of the three most extensively studied Exo1 polymorphisms (Pro757Leu, Glu589Lys, and Glu670Gly) on cancer susceptibility. The related studies published before August 5, 2015, were collected by searching the PubMed and EMBASE databases. We found 16 publications containing studies that were eligible for our study, including 10 studies for Pro757Leu polymorphism (4,093 cases and 3,834 controls), 12 studies for Glu589Lys polymorphism (6,479 cases and 6,550 controls), and 7 studies for Glu670Gly polymorphism (3,700 cases and 3,496 controls). Pooled odds ratios and 95% confidence intervals were used to assess the strength of the associations, and all the statistical analyses were calculated using the software program STATA version 12.0. Our results revealed that the Pro757Leu polymorphism was significantly associated with a reduced cancer risk, whereas an inverse association was found for the Glu589Lys polymorphism. Furthermore, subgroup analysis of smoking status indicated that the Glu589Lys polymorphism was significantly associated with an increased cancer risk in smokers, but not in nonsmokers. However, no evidence was found for an association between the Glu670Gly polymorphism and cancer risk. In conclusion, this meta-analysis suggests that the Pro757Leu polymorphism may provide protective effects against cancer, while the Glu589Lys polymorphism may be a risk factor for cancer. Moreover, the Glu670Gly polymorphism may have no influence on cancer susceptibility. In the future, large-scaled and well-designed studies are needed to achieve a more precise and comprehensive result. PMID:26966378

  7. The Association between KCNQ1 Gene Polymorphism and Type 2 Diabetes Risk: A Meta-Analysis

    PubMed Central

    Shen, Xizhong; Cai, Yu

    2012-01-01

    Background KCNQ1 (potassium voltage-gated channel KQT-like sub-family, member 1) encodes a pore-forming subunit of a voltage-gated K+ channel (KvLQT1) that plays a key role for the repolarization of the cardiac action potential as well as water and salt transport in epithelial tissues. Recently, genome-wide association studies have identified KCNQ1 as a type 2 diabetes (T2D) susceptibility gene in populations of Asian descent. After that, a number of studies reported that the rs2237892 and rs2237895 polymorphism in KCNQ1 has been implicated in T2D risk. However, studies on the association between these polymorphism and T2D remain conflicting. To investigate this inconsistency, we performed this meta-analysis. Methods Databases including Pubmed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Potential sources of heterogeneity were also assessed by subgroup analysis and meta-regression. Results A total of 25 articles involving 70,577 T2D cases and 99,068 controls were included. Overall, the summary odds ratio of C allele for T2D was 1.32 (95% CI 1.26–1.38; P<10−5) and 1.24 (95% CI: 1.20–1.29; P<10−5) for KCNQ1 rs2237892 and rs2237895 polymorphisms, respectively. Significant results were also observed using co-dominant, dominant and recessive genetic models. After stratifying by ethnicity, sample size, and diagnostic criteria, significant associations were also obtained. Conclusions This meta-analysis suggests that the rs2237892 and rs2237895 polymorphisms in KCNQ1 are associated with elevated type 2 diabetes susceptibility. PMID:23133642

  8. The Association of Diabetes Mellitus with Clinical Outcomes after Coronary Stenting: A Meta-Analysis

    PubMed Central

    Jiang, Hai-Xing; Hu, Bang-Li; Tao, Lin; Xie, Min-zhi

    2013-01-01

    Background Previous studies have shown inconsistent results on the association between diabetes mellitus (DM) and some clinical outcomes. We conducted a meta-analysis of observational studies to assess effect of DM on clinical outcomes after coronary stenting. Methods We searched for studies without language restriction in PubMed, Embase and Cochrane library prior to 2012. The clinical outcomes including in-stent restenosis (ISR), major adverse cardiac events (MACE), stent thrombosis (ST), target lesion revascularization (TLR) and target vessel revascularization (TVR). Adjusted odds ratio (OR), and the corresponding 95% confidence interval (95% CI) was summarized. Results 55 studies involving 128,084 total patients (38,416 DM patients and 89,668 controls) were eligible for our analysis. Overall, there were significant associations between DM and ISR (OR = 1.70, 95% CI: 1.53–1.89, I2 = 0.0%), MACE (OR = 1.54, 95% CI: 1.36–1.73, I2 = 29.0%), ST (OR = 2.01, 95% CI: 1.36–2.97, I2 = 47.7%), TLR (OR = 1.46, 95% CI: 1.26–1.68, I2 = 43.3%) as well as TVR (OR = 1.33, 95% CI: 1.17–1.51, I2 = 48.3). Subgroup analysis showed that the associations were similar between BMS and DES implantation. Moreover, there was no significant association in the ST subgroup after 1–3 years follow-up. Conclusions Our meta-analysis suggests that after coronary stent implantation, DM is associated with ISR, MACE, ST, TLR and TVR. DM appears to be a vital risk factor of these clinical outcomes. PMID:24066025

  9. Association between selenium levels and oesophageal adenocarcinoma risk: evidence from a meta-analysis.

    PubMed

    Hong, Bin; Huang, Lihong; Mao, Ning; Xiong, Tao; Li, Chao; Hu, Liangbo; Du, Ying

    2016-08-01

    Quantification of the association between selenium and risk of oesophageal adenocarcinoma (OAC) is still conflicting. The purpose of this meta-analysis is to explore the relationship between selenium levels and OAC risk. PubMed and Web of Knowledge were searched for the related articles. Pooled relative risks (RRs) with 95% confidence intervals (CIs) from random effects models were calculated. Sensitivity analysis and publication bias were conducted. Dose-response relationship was assessed by restricted cubic spline and variance-weighted least squares regression analysis. Five articles involving 748 OAC cases were included in this meta-analysis. Pooled results suggest that higher selenium level was not significantly associated with the risk of OAC (summary RRs=1.08, 95% CIs=0.84-1.39, I(2)=0%). Besides, no significant association was found in case-control studies (summary RRs=1.13, 95% CIs=0.84-1.52, I(2)=0%) or cohort studies (summary RRs=0.99, 95% CIs=0.55-1.78, I(2)=32.6%). A linear dose-response relationship was attested that an increase in dietary selenium intake of 10 μg/day is marginally associated with 1% increase in the risk of developing OAC (summary RRs=1.01, 95% CIs=0.99-1.03), but not statistically significant. No publication bias was found. In conclusion, our analysis indicated that a higher selenium level was not significantly associated with the risk of OAC. The relevant further studies are warranted. PMID:27190131

  10. Meta-analysis of the association of MTHFR polymorphisms with multiple myeloma risk.

    PubMed

    Ma, Li-Min; Ruan, Lin-Hai; Yang, Hai-Ping

    2015-01-01

    The association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with multiple myeloma (MM) risk has been explored, but the results remain controversial. Thus, a meta-analysis was performed to provide a comprehensively estimate. The case-control studies about MTHFR C677T and A1298C polymorphisms with MM risk were collected by searching PubMed, Elsevier, China National Knowledge Infrastructure and Wanfang Databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of association. Overall, no significant association was found between MTHFR A1298C polymorphism and MM risk under all four genetic models (AC vs. AA, OR = 0.99, 95%CI = 0.82-1.20; CC vs. AA, OR = 1.14, 95%CI = 0.77-1.68; recessive model, OR = 1.10, 95%CI = 0.76-1.59; dominant model, OR = 1.01, 95%CI = 0.84-1.22). The risk was also not significantly altered for C677T polymorphism and MM in overall comparisons (CT vs. CC, OR = 1.04, 95%CI = 0.93-1.17; TT vs. CC, OR = 1.16, 95%CI = 0.98-1.37; recessive model, OR = 1.13, 95%CI = 0.98-1.32; dominant model, OR = 1.07, 95%CI = 0.96-1.20). In subgroup analyses by ethnicity, no significant association was observed in both Caucasians and Asians. This meta-analysis suggested that MTHFR polymorphisms were not associated with MM risk. PMID:26022785

  11. Meta-analysis of the association of MTHFR polymorphisms with multiple myeloma risk

    PubMed Central

    Ma, Li-Min; Ruan, Lin-Hai; Yang, Hai-Ping

    2015-01-01

    The association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with multiple myeloma (MM) risk has been explored, but the results remain controversial. Thus, a meta-analysis was performed to provide a comprehensively estimate. The case-control studies about MTHFR C677T and A1298C polymorphisms with MM risk were collected by searching PubMed, Elsevier, China National Knowledge Infrastructure and Wanfang Databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of association. Overall, no significant association was found between MTHFR A1298C polymorphism and MM risk under all four genetic models (AC vs. AA, OR = 0.99, 95%CI = 0.82-1.20; CC vs. AA, OR = 1.14, 95%CI = 0.77-1.68; recessive model, OR = 1.10, 95%CI = 0.76-1.59; dominant model, OR = 1.01, 95%CI = 0.84-1.22). The risk was also not significantly altered for C677T polymorphism and MM in overall comparisons (CT vs. CC, OR = 1.04, 95%CI = 0.93-1.17; TT vs. CC, OR = 1.16, 95%CI = 0.98-1.37; recessive model, OR = 1.13, 95%CI = 0.98-1.32; dominant model, OR = 1.07, 95%CI = 0.96-1.20). In subgroup analyses by ethnicity, no significant association was observed in both Caucasians and Asians. This meta-analysis suggested that MTHFR polymorphisms were not associated with MM risk. PMID:26022785

  12. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

    PubMed Central

    Postmus, Iris; Trompet, Stella; Deshmukh, Harshal A.; Barnes, Michael R.; Li, Xiaohui; Warren, Helen R.; Chasman, Daniel I.; Zhou, Kaixin; Arsenault, Benoit J.; Donnelly, Louise A.; Wiggins, Kerri L.; Avery, Christy L.; Griffin, Paula; Feng, QiPing; Taylor, Kent D.; Li, Guo; Evans, Daniel S.; Smith, Albert V.; de Keyser, Catherine E.; Johnson, Andrew D.; de Craen, Anton J. M.; Stott, David J.; Buckley, Brendan M.; Ford, Ian; Westendorp, Rudi G. J.; Eline Slagboom, P.; Sattar, Naveed; Munroe, Patricia B.; Sever, Peter; Poulter, Neil; Stanton, Alice; Shields, Denis C.; O’Brien, Eoin; Shaw-Hawkins, Sue; Ida Chen, Y.-D.; Nickerson, Deborah A.; Smith, Joshua D.; Pierre Dubé, Marie; Matthijs Boekholdt, S.; Kees Hovingh, G.; Kastelein, John J. P.; McKeigue, Paul M.; Betteridge, John; Neil, Andrew; Durrington, Paul N.; Doney, Alex; Carr, Fiona; Morris, Andrew; McCarthy, Mark I.; Groop, Leif; Ahlqvist, Emma; Bis, Joshua C.; Rice, Kenneth; Smith, Nicholas L.; Lumley, Thomas; Whitsel, Eric A.; Stürmer, Til; Boerwinkle, Eric; Ngwa, Julius S.; O’Donnell, Christopher J.; Vasan, Ramachandran S.; Wei, Wei-Qi; Wilke, Russell A.; Liu, Ching-Ti; Sun, Fangui; Guo, Xiuqing; Heckbert, Susan R; Post, Wendy; Sotoodehnia, Nona; Arnold, Alice M.; Stafford, Jeanette M.; Ding, Jingzhong; Herrington, David M.; Kritchevsky, Stephen B.; Eiriksdottir, Gudny; Launer, Leonore J.; Harris, Tamara B.; Chu, Audrey Y.; Giulianini, Franco; MacFadyen, Jean G.; Barratt, Bryan J.; Nyberg, Fredrik; Stricker, Bruno H.; Uitterlinden, André G.; Hofman, Albert; Rivadeneira, Fernando; Emilsson, Valur; Franco, Oscar H.; Ridker, Paul M.; Gudnason, Vilmundur; Liu, Yongmei; Denny, Joshua C.; Ballantyne, Christie M.; Rotter, Jerome I.; Adrienne Cupples, L.; Psaty, Bruce M.; Palmer, Colin N. A.; Tardif, Jean-Claude; Colhoun, Helen M.; Hitman, Graham; Krauss, Ronald M.; Wouter Jukema, J; Caulfield, Mark J.; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M.; Bramon, Elvira; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N. A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C. A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Donnelly, Peter; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Barroso, Ines; Deloukas, Panos; Mathew, Christopher G.; Blackwell, Jenefer M.; Brown, Matthew A.; Corvin, Aiden; McCarthy, Mark I.; Spencer, Chris C. A.

    2014-01-01

    Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response. PMID:25350695

  13. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.

    PubMed

    Postmus, Iris; Trompet, Stella; Deshmukh, Harshal A; Barnes, Michael R; Li, Xiaohui; Warren, Helen R; Chasman, Daniel I; Zhou, Kaixin; Arsenault, Benoit J; Donnelly, Louise A; Wiggins, Kerri L; Avery, Christy L; Griffin, Paula; Feng, QiPing; Taylor, Kent D; Li, Guo; Evans, Daniel S; Smith, Albert V; de Keyser, Catherine E; Johnson, Andrew D; de Craen, Anton J M; Stott, David J; Buckley, Brendan M; Ford, Ian; Westendorp, Rudi G J; Slagboom, P Eline; Sattar, Naveed; Munroe, Patricia B; Sever, Peter; Poulter, Neil; Stanton, Alice; Shields, Denis C; O'Brien, Eoin; Shaw-Hawkins, Sue; Chen, Y-D Ida; Nickerson, Deborah A; Smith, Joshua D; Dubé, Marie Pierre; Boekholdt, S Matthijs; Hovingh, G Kees; Kastelein, John J P; McKeigue, Paul M; Betteridge, John; Neil, Andrew; Durrington, Paul N; Doney, Alex; Carr, Fiona; Morris, Andrew; McCarthy, Mark I; Groop, Leif; Ahlqvist, Emma; Bis, Joshua C; Rice, Kenneth; Smith, Nicholas L; Lumley, Thomas; Whitsel, Eric A; Stürmer, Til; Boerwinkle, Eric; Ngwa, Julius S; O'Donnell, Christopher J; Vasan, Ramachandran S; Wei, Wei-Qi; Wilke, Russell A; Liu, Ching-Ti; Sun, Fangui; Guo, Xiuqing; Heckbert, Susan R; Post, Wendy; Sotoodehnia, Nona; Arnold, Alice M; Stafford, Jeanette M; Ding, Jingzhong; Herrington, David M; Kritchevsky, Stephen B; Eiriksdottir, Gudny; Launer, Leonore J; Harris, Tamara B; Chu, Audrey Y; Giulianini, Franco; MacFadyen, Jean G; Barratt, Bryan J; Nyberg, Fredrik; Stricker, Bruno H; Uitterlinden, André G; Hofman, Albert; Rivadeneira, Fernando; Emilsson, Valur; Franco, Oscar H; Ridker, Paul M; Gudnason, Vilmundur; Liu, Yongmei; Denny, Joshua C; Ballantyne, Christie M; Rotter, Jerome I; Adrienne Cupples, L; Psaty, Bruce M; Palmer, Colin N A; Tardif, Jean-Claude; Colhoun, Helen M; Hitman, Graham; Krauss, Ronald M; Wouter Jukema, J; Caulfield, Mark J

    2014-01-01

    Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response. PMID:25350695

  14. Association between seven common OPG genetic polymorphisms and osteoporosis risk: a meta-analysis.

    PubMed

    Guo, Liang; Tang, Ke; Quan, Zhengxue; Zhao, Zenghui; Jiang, Dianming

    2014-01-01

    Functional polymorphisms of the osteoprotegerin (OPG) gene are known to be involved in bone mineral density and the development of osteoporosis; however, some conflicting results have been reported. The aim of this meta-analysis is to provide a relatively comprehensive assessment of the relationship between seven common OPG genetic polymorphisms (T149C, A163G, G209A, T245G, T950C, G1181C, and C1217T) and osteoporosis risk. A literature search for eligible studies published before August 1st, 2013 was conducted in PubMed, Embase, Web of Science, Cochrane Library, and CNKI (China National Knowledge Infrastructure) databases. Pooled odds ratios and their corresponding 95% confidence intervals were used to evaluate the strength of the association under fixed- or random-effect models according to a heterogeneity test. All analyses were performed using the STATA software, version 12.0. Fourteen case-control studies with a total of 2383 osteoporosis cases and 2280 healthy controls were included in this meta-analysis. Among the seven polymorphisms, A163G and G1181C revealed significant associations with osteoporosis risk. For A163G (rs3102735), the combined results showed that the G allele of the A163G polymorphism may be associated with an increased risk of osteoporosis. Stratified analyses showed that the magnitude of the effect was similar in Caucasian and postmenopausal woman subgroups. For G1181C (rs2073618), however, we found that individuals with the C allele of the G1181C polymorphism had a decreased risk of osteoporosis, especially in Asian and postmenopausal woman subgroups. In summary, this meta-analysis indicated that the G allele of the OPG A163G polymorphism might increase osteoporosis risk in Caucasians, whereas individuals with the C allele of the G1181C polymorphism had a decreased risk of osteoporosis, especially in Asians. Both of these effects were observed in postmenopausal women. These polymorphisms could probably be used with other genetic markers

  15. Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk: A Meta-Analysis Study

    PubMed Central

    Liu, Jibin; Shen, Biao; Shi, Minxin; Cai, Jing

    2016-01-01

    Background Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM) risk. Methods Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015). Study-specific risk estimates were pooled under the random-effects model. Results Two case-control studies (846 MM patients and 843 controls) and five cohort studies (including 844,246 participants and 5,737 MM cases) were identified. For caffeinated coffee, the pooled relative risk (RR) of MM was 0.81 [95% confidential interval (95% CI) = 0.68–0.97; P-value for Q-test = 0.003; I2 = 63.5%] for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 (95% CI = 0.912–0.999) for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326). Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81–1.05; P-value for Q-test = 0.967; I2 = 0%; highest versus lowest quantity of intake). Conclusions This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings. PMID:26816289

  16. Association between diabetes mellitus and osteoarthritis: systematic literature review and meta-analysis

    PubMed Central

    Louati, Karine; Vidal, Céline; Berenbaum, Francis; Sellam, Jérémie

    2015-01-01

    Objectives To investigate the prevalence of osteoarthritis (OA) in patients with diabetes mellitus (DM) and prevalence of DM in patients with OA and whether OA and DM are associated. Design A systematic literature review and meta-analysis. We included cohort, case–control and cross-sectional studies assessing the number of patients with DM and/or OA. The mean prevalence of OA among patients with DM and DM among patients with OA was calculated. Data from trials assessing an association of diabetes and OA were pooled and results are presented as unadjusted OR and 95% CI. Results From the 299 publications, we included 49 studies in the analysis, including 28 cross-sectional studies, 11 cohort studies and 10 case–control studies. In all, 21, 5 and 23 articles involved patients with OA exclusively, patients with DM and the general population, respectively. For 5788 patients with DM, the mean OA prevalence was 29.5±1.2%. For 645 089 patients with OA, the prevalence of DM was 14.4±0.1%. The risk of OA was greater in the DM than non-DM population (OR=1.46 (1.08 to 1.96), p=0.01), as was DM in the OA than non-OA population (OR=1.41 (1.21 to 1.65), p<0.00 001). Among the 12 studies reporting an OR adjusted on at least the body mass index, 5 showed no association of DM and OA and 7 identified DM as an independent risk factor. Conclusions This meta-analysis highlights a high frequency of OA in patients with DM and an association between both diseases, representing a further step towards the individualisation of DM-related OA within a metabolic OA phenotype. PMID:26535137

  17. Meta-analysis of genome-wide association studies for personality

    PubMed Central

    de Moor, Marleen H.M.; Costa, Paul T.; Terracciano, Antonio; Krueger, Robert F.; de Geus, Eco J.C.; Toshiko, Tanaka; Penninx, Brenda W.J.H.; Esko, Tõnu; Madden, Pamela A F; Derringer, Jaime; Amin, Najaf; Willemsen, Gonneke; Hottenga, Jouke-Jan; Distel, Marijn A.; Uda, Manuela; Sanna, Serena; Spinhoven, Philip; Hartman, Catharina A.; Sullivan, Patrick; Realo, Anu; Allik, Jüri; Heath, Andrew C; Pergadia, Michele L; Agrawal, Arpana; Lin, Peng; Grucza, Richard; Nutile, Teresa; Ciullo, Marina; Rujescu, Dan; Giegling, Ina; Konte, Bettina; Widen, Elisabeth; Cousminer, Diana L; Eriksson, Johan G.; Palotie, Aarno; Luciano, Michelle; Tenesa, Albert; Davies, Gail; Lopez, Lorna M.; Hansell, Narelle K.; Medland, Sarah E.; Ferrucci, Luigi; Schlessinger, David; Montgomery, Grant W.; Wright, Margaret J.; Aulchenko, Yurii S.; Janssens, A.Cecile J.W.; Oostra, Ben A.; Metspalu, Andres; Abecasis, Gonçalo R.; Deary, Ian J.; Räikkönen, Katri; Bierut, Laura J.; Martin, Nicholas G.; van Duijn, Cornelia M.; Boomsma, Dorret I.

    2013-01-01

    Personality can be thought of as a set of characteristics that influence people’s thoughts, feelings, and behaviour across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in ten discovery samples (17 375 adults) and five in-silico replication samples (3 294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data were available of ~2.4M Single Nucleotide Polymorphisms (SNPs; directly typed and imputed using HAPMAP data). In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P = 2.8 × 10−8 and 3.1 × 10−8) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P = 4.9 × 10−8). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In-silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness. PMID:21173776

  18. Association between Breastfeeding and Endometrial Cancer Risk: Evidence from a Systematic Review and Meta-Analysis

    PubMed Central

    Wang, Lianlian; Li, Jingxi; Shi, Zhan

    2015-01-01

    Quantification of the association between breastfeeding and risk of endometrial cancer is still conflicting. We therefore conducted a meta-analysis to assess the association between breastfeeding and endometrial cancer risk. Pertinent studies were identified by a search of PubMed and Web of Knowledge through April 2015. A random effect model was used to combine the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationships were assessed by restricted cubic spline and variance-weighted least squares regression analysis. Fourteen articles involving 5158 endometrial cancer cases and 706,946 participants were included in this meta-analysis. Pooled results suggested that breastfeeding significantly reduced the risk of endometrial cancer (summary relative risk (RR): 0.77, 95% CI: 0.62–0.96, I2: 63.0%), especially in North America (summary RR: 0.87, 95% CI: 0.79–0.95). A linear dose-response relationship was found, with the risk of endometrial cancer decreased by 2% for every one-month increase in the duration of breastfeeding (summary RR: 0.98, 95% CI: 0.97–0.99). Our analysis suggested that breastfeeding, particularly a longer duration of breastfeeding, was inversely associated with the risk of endometrial cancer, especially in North America, but not in Europe and Asia, probably due to the small number of cases included. Due to this limitation, further studies originating in other countries are required to assess the association between breastfeeding and endometrial cancer risk. PMID:26184301

  19. The association between noise exposure and blood pressure and ischemic heart disease: a meta-analysis.

    PubMed Central

    van Kempen, Elise E M M; Kruize, Hanneke; Boshuizen, Hendriek C; Ameling, Caroline B; Staatsen, Brigit A M; de Hollander, Augustinus E M

    2002-01-01

    It has been suggested that noise exposure is associated with blood pressure changes and ischemic heart disease risk, but epidemiologic evidence is still limited. Furthermore, most reviews investigating these relations were not carried out in a systematic way, which makes them more prone to bias. We conducted a meta-analysis of 43 epidemiologic studies published between 1970 and 1999 that investigate the relation between noise exposure (both occupational and community) and blood pressure and/or ischemic heart disease (International Classification of Diseases, Ninth Revision, codes 410-414). We studied a wide range of effects, from blood pressure changes to a myocardial infarction. With respect to the association between noise exposure and blood pressure, small blood pressure differences were evident. Our meta-analysis showed a significant association for both occupational noise exposure and air traffic noise exposure and hypertension: We estimated relative risks per 5 dB(A) noise increase of 1.14 (1.01-1.29) and 1.26 (1.14-1.39), respectively. Air traffic noise exposure was positively associated with the consultation of a general practitioner or specialist, the use of cardiovascular medicines, and angina pectoris. In cross-sectional studies, road traffic noise exposure increases the risk of myocardial infarction and total ischemic heart disease. Although we can conclude that noise exposure can contribute to the prevalence of cardiovascular disease, the evidence for a relation between noise exposure and ischemic heart disease is still inconclusive because of the limitations in exposure characterization, adjustment for important confounders, and the occurrence of publication bias. PMID:11882483

  20. Association between two interleukin-2 gene polymorphisms and cancer susceptibility: a meta-analysis

    PubMed Central

    Zhang, Meng; Tan, Xiuxiu; Huang, Junjie; Xie, Lijuan; Wang, Hao; Shi, Jizhou; Lu, Wei; Lv, Zhaojie; Mei, Hongbing; Liang, Chaozhao

    2016-01-01

    Background Several epidemiological studies have illustrated that polymorphisms in interleukin-2 (IL-2) were associated with diverse cancer types. However, recently published statistics were inconsistent and inconclusive. Therefore, the current meta-analysis was performed to elaborate the effects of IL-2 polymorphisms (rs2069762 and rs2069763) on cancer susceptibility. Material and methods A total of 5,601 cancer cases and 7,809 controls from 21 published case–control studies were enrolled in our meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between IL-2 polymorphisms and cancer susceptibility. Results Our study demonstrated an increased susceptibility to cancer in rs2069762 (G vs T: OR =1.268, 95% CI =1.113–1.445; GG vs TT: OR =1.801, 95% CI =1.289–2.516; GT vs TT: OR =1.250, 95% CI =1.061–1.473; GG + GT vs TT: OR =1.329, 95% CI =1.118–1.579; GG vs GT + TT: OR =1.536, 95% CI =1.162–2.030). In the subgroup analysis, increased susceptibility to cancer was identified in the hospital-based group and PHWE<0.05 (P-value of the Hardy–Weinberg equilibrium [HWE]) group. In addition, a positive association with cancer susceptibility was observed among both Chinese and non-Chinese. However, no relationship was detected between the rs2069763 polymorphism of IL-2 and cancer susceptibility. Conclusion To conclude, rs2069762 polymorphism of IL-2 contributed to an increased susceptibility to cancer, whereas no association was identified between rs2069763 polymorphism and cancer susceptibility. Further detailed studies are warranted to confirm our findings. PMID:27143914

  1. Associations of Quality of Life with Service Satisfaction in Psychotic Patients: A Meta-Analysis

    PubMed Central

    Petkari, Eleni; Pietschnig, Jakob

    2015-01-01

    Background Quality of life (QoL) has gained increasing attention as a desired outcome of psychosocial treatments targeting psychotic patients. Yet, the relationship between the patients’ satisfaction with services and QoL has not been clearly established, perhaps due to the multidimensionality of the QoL concept and the variability in its assessment. Aim This is the first systematic meta-analysis of all available evidence assessing the relationship between QoL and service satisfaction. Methods: In all, 19 studies reporting data of 21 independent samples (N = 5,337) were included in the present meta-analysis. In moderator analyses, effects of age, sex, diagnoses (schizophrenia vs. other psychoses), treatment context (inpatients vs. outpatients), study design (cross-sectional vs. longitudinal), and QoL domain (subjective vs. health-related) were examined. Results Analyses revealed a highly significant medium-sized effect (r = .30, p < .001) for the associations of QoL and service satisfaction. Effect sizes were significantly stronger for subjective than health-related quality of life (r = .35 vs. r = .14, respectively). Moreover, associations with subjective QoL remained largely robust when accounting for moderating variables, although there was a trend of stronger associations for outpatients compared to inpatients. In contrast, effect sizes for health-related QoL were small and only observable for samples with longitudinal designs. Conclusion Associations between QoL and service satisfaction appear to be robust but are differentiated in regard to QoL domain. Our findings suggest that agents responsible for service design and implementation need to take the patients’ perception of the service adequacy for achieving QoL enhancement into account. PMID:26275139

  2. Factors Associated with Visceral Leishmaniasis in the Americas: A Systematic Review and Meta-Analysis

    PubMed Central

    Belo, Vinícius Silva; Werneck, Guilherme Loureiro; Barbosa, David Soeiro; Simões, Taynãna César; Nascimento, Bruno Warlley Leandro; da Silva, Eduardo Sérgio; Struchiner, Claudio José

    2013-01-01

    Background Still today, more than 30 years after the beginning of the process of visceral leishmaniasis' urbanization, there is little knowledge about the risk factors for its occurrence, despite their relevance to the control and understanding of disease dynamics. The present study is the first systematic review with meta-analysis about factors associated with Leishmania infantum infection in humans in the Americas. Methods and Findings After searching different databases, consultations to the reference lists of articles and to experts in the field, 51 studies were reviewed. Theoretical discussions or meta-analysis of p-values or of effect sizes were used to pool information about each variable. The Q test and the I2 statistic were used to assess heterogeneities among the studies. Male sex was associated with visceral leishmaniasis in studies which used the leishmanin skin test for diagnosis and in those where the outcome was the clinical disease; the opposite occurred when serological diagnosis was applied. Younger individuals were less frequently infected than adults, but were more prone to illness. Although with different levels of evidence and of heterogeneity, the presence of dogs at home, higher dog seropositivity in nearby areas, lower socioeconomic status and highly vegetated areas were associated with L. infantum infection. This was not noticed for the presence of chickens in the house and with nutritional status. Susceptibilities to bias and limitations in the analysis and in the description of results were often identified in the studies analyzed. Conclusions Results showed the existence of consistent patterns for some of the factors analyzed and should be taken into account in developing more effective and well-targeted control measures. Studies must be conducted in new areas of the continent, with improved methodological quality and prioritizing the investigation of the patterns identified and their causes, as well as variables for which knowledge is

  3. Obsessive-compulsive disorder is associated with broad impairments in executive function: A meta-analysis

    PubMed Central

    Snyder, Hannah R.; Kaiser, Roselinde H.; Warren, Stacie L.; Heller, Wendy

    2014-01-01

    Obsessive-compulsive disorder (OCD) is a serious and often chronically disabling condition. The current dominant model of OCD focuses on abnormalities in prefrontal-striatal circuits that support executive function (EF). While there is growing evidence for EF impairments associated with OCD, results have been inconsistent, making the nature and magnitude of these impairments controversial. The current meta-analysis uses random-effects models to synthesize 110 previous studies that compared participants with OCD to healthy control participants on at least one neuropsychological measure of EF. The results indicate that individuals with OCD are impaired on tasks measuring most aspects of EF, consistent with broad impairment in EF. EF deficits were not explained by general motor slowness or depression. Effect sizes were largely stable across variation in demographic and clinical characteristics of samples, although medication use, age, and gender moderated some effects. PMID:25755918

  4. Association between psoriasis and chronic obstructive pulmonary disease: A systematic review and meta-analysis.

    PubMed

    Ungprasert, Patompong; Srivali, Narat; Thongprayoon, Charat

    2016-08-01

    Psoriasis has been linked to an increased risk of several co-morbidities. However, its association with chronic obstructive pulmonary disease (COPD) remains unclear. To further characterize this relationship, we conducted a systematic review and meta-analysis of case-control and cross-sectional studies that compared the risk of COPD in patients with psoriasis versus non-psoriasis participants. Generic inverse variance method of DerSimonian and Laird was used to combine all the point estimates. Out of 502 potentially relevant articles, seven studies met our inclusion criteria and were included in the data analysis. The pooled odds ratio of COPD in patients with psoriasis versus control was 1.45 (95% CI, 1.21-1.73). The statistical heterogeneity was high with an I(2) of 91%. Therefore, our study provided evidence to support the increased risk of COPD among patients with psoriasis. PMID:26458363

  5. Genetic association analysis and meta-analysis of imputed SNPs in longitudinal studies

    PubMed Central

    Subirana, Isaac; González, Juan R

    2014-01-01

    In this paper we propose a new method to analyze time-to-event data in longitudinal genetic studies. This method address the fundamental problem of incorporating uncertainty when analyzing survival data and imputed single nucleotide polymorphisms (SNPs) from genomewide association studies (GWAS). Our method incorporates uncertainty in the likelihood function, the opposite of existing methods that incorporate the uncertainty in the design matrix. Through simulation studies and real data analyses, we show that our proposed method is unbiased and provides powerful results. We also show how combining results from different GWAS (meta-analysis) may lead to wrong results when effects are not estimated using our approach. The model is implemented in an R package that is designed to analyze uncertainty not only arising from imputed SNPs, but also from copy number variants (CNVs). PMID:23595425

  6. Peer Cybervictimization Among Adolescents and the Associated Internalizing and Externalizing Problems: A Meta-Analysis.

    PubMed

    Fisher, Benjamin W; Gardella, Joseph H; Teurbe-Tolon, Abbie R

    2016-09-01

    Numerous adolescents in the United States experience peer cybervictimization, which is associated with a series of internalizing (e.g., depression, anxiety, anger) and externalizing (e.g., aggression, substance use, risky sexual behavior) problems. The current study provides a systematic review and meta-analysis of existing research on these relationships. Included in the meta-analyses are 239 effect sizes from 55 reports, representing responses from 257,678 adolescents. The results of a series of random effects meta-analyses using robust variance estimation indicated positive and significant relationships between peer cybervictimization and a series of internalizing and externalizing problems, with point estimates of this relationship ranging from Pearson's r = .14 to .34. Implications for research and practice are discussed. PMID:27447707

  7. Association between the level of circulating adiponectin and prediabetes: A meta-analysis

    PubMed Central

    Lai, Huasheng; Lin, Nie; Xing, Zhenzhen; Weng, Huanhuan; Zhang, Hua

    2015-01-01

    Aims/Introduction Adiponectin has been proposed to have an essential role in the regulation of insulin sensitivity and metabolism, but previous studies on levels of adiponectin in prediabetes remain inconsistent. The present study aimed to assess the differences of adiponectin levels between prediabetes patients and healthy controls by carrying out a meta-analysis. Materials and Methods We carried out a systematic literature search of PubMed, EMBASE, and other databases for case–control studies and cohort studies measuring adiponectin levels in serum or plasma from prediabetes patients and healthy controls. The pooled weighted mean difference (WMD) and 95% confidence interval (CI) were used to estimate the association between adiponectin levels and prediabetes. Results Three cohort studies and 15 case–control studies with a total of 41,841 participants were included in the meta-analysis. The results showed that circulating adiponectin levels in prediabetes patients were significantly lower than that of healthy controls (WMD –1.694 μg/mL; 95% CI –2.151, –1.237; P < 0.001). Subgroup analysis showed more significant differences between prediabetes patients and healthy controls when the ratio of the homeostatic model assessment of insulin resistance was >2.12 (WMD −2.95 μg/mL; 95% CI –4.103, –1.806; P < 0.001) and average age was >60 years (WMD −2.20 μg/mL; 95% CI –3.207, –1.201; P < 0.001). Additionally, WMD in adiponectin showed a trend of direct correlation in subgroups of homeostatic model assessment of insulin resistance ratio, body mass index and age. Conclusions The present meta-analysis supports adiponectin levels in prediabetes patients being lower than that of healthy controls,indicating that the level of circulating adiponectin decreases before the onset of diabetes. PMID:26221520

  8. Association between the ERCC5 Asp1104His Polymorphism and Cancer Risk: A Meta-Analysis

    PubMed Central

    He, Jing; Shi, Ting-Yan; Xia, Kai-Qin; Qiu, Li-Xin; Wei, Qing-Yi

    2012-01-01

    Background Excision repair cross complementing group 5 (ERCC5 or XPG) plays an important role in regulating DNA excision repair, removal of bulky lesions caused by environmental chemicals or UV light. Mutations in this gene cause a rare autosomal recessive syndrome, and its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity phenotype and cancer risk. However, a series of epidemiological studies on the association between the ERCC5 Asp1104His polymorphism (rs17655, G>C) and cancer susceptibility generated conflicting results. Methodology/Principal Findings To derive a more precise estimation of the association between the ERCC5 Asp1104His polymorphism and overall cancer risk, we performed a meta-analysis of 44 published case-control studies, in which a total of 23,490 cases and 27,168 controls were included. To provide additional biological plausibility, we also assessed the genotype-gene expression correlation from the HapMap phase II release 23 data with 270 individuals from 4 ethnic populations. When all studies were pooled, we found no statistical evidence for a significantly increased cancer risk in the recessive genetic models (His/His vs. Asp/Asp: OR = 0.99, 95% CI: 0.92–1.06, P = 0.242 for heterogeneity or His/His vs. Asp/His + Asp/Asp: OR = 0.98, 95% CI: 0.93–1.03, P = 0.260 for heterogeneity), nor in further stratified analyses by cancer type, ethnicity, source of controls and sample size. In the genotype-phenotype correlation analysis from 270 individuals, we consistently found no significant correlation of the Asp1104His polymorphism with ERCC5 mRNA expression. Conclusions/Significance This meta-analysis suggests that it is unlikely that the ERCC5 Asp1104His polymorphism may contribute to individual susceptibility to cancer risk. PMID:22815677

  9. The association between physical activity and gastroesophageal cancer: systematic review and meta-analysis.

    PubMed

    Behrens, Gundula; Jochem, Carmen; Keimling, Marlen; Ricci, Cristian; Schmid, Daniela; Leitzmann, Michael Fred

    2014-03-01

    Physical activity may decrease gastroesophageal cancer risk through a reduction of oxidative stress and decreased chronic inflammation, yet few epidemiologic studies have been able to report a clear inverse association between physical activity and gastroesophageal cancer. Because no meta-analysis has investigated the relation of physical activity to gastroesophageal cancer, we conducted a comprehensive systematic review and meta-analysis according to the PRISMA guidelines based on 24 studies with a total of 15,745 cases. When we compared high versus low physical activity levels and summarized associations according to anatomic site and tumor histology, risk reductions were evident for esophageal adenocarcinoma [relative risk (RR) = 0.79, 95% confidence interval (CI) = 0.66-0.94], gastric cardia adenocarcinoma (RR = 0.83, 95% CI = 0.69-0.99) and gastric non-cardia adenocarcinoma (RR = 0.72, 95% CI = 0.62-0.84). The risk reduction for esophageal squamous cell carcinoma (RR = 0.94, 95% CI = 0.41-2.16) became statistically significant (RR = 0.66, 95% CI = 0.46-0.96) after excluding an influential study. The test for heterogeneity by gastroesophageal cancer subtype was statistically non-significant (p-difference = 0.71). The RR of total gastroesophageal cancer for high versus low physical activity was 0.82 (95% CI = 0.74-0.90). A dose-response analysis of frequency of physical activity and total gastroesophageal cancer risk revealed that the greatest risk reduction was achieved among those engaging in moderate to vigorous physical activity five times per week (RR = 0.67, 95% CI = 0.58-0.79). Our results provide support for an inverse relation of physical activity, in particular exercise frequency, to gastroesophageal cancer risk. PMID:24705782

  10. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

    PubMed

    Cornelis, M C; Byrne, E M; Esko, T; Nalls, M A; Ganna, A; Paynter, N; Monda, K L; Amin, N; Fischer, K; Renstrom, F; Ngwa, J S; Huikari, V; Cavadino, A; Nolte, I M; Teumer, A; Yu, K; Marques-Vidal, P; Rawal, R; Manichaikul, A; Wojczynski, M K; Vink, J M; Zhao, J H; Burlutsky, G; Lahti, J; Mikkilä, V; Lemaitre, R N; Eriksson, J; Musani, S K; Tanaka, T; Geller, F; Luan, J; Hui, J; Mägi, R; Dimitriou, M; Garcia, M E; Ho, W-K; Wright, M J; Rose, L M; Magnusson, P K E; Pedersen, N L; Couper, D; Oostra, B A; Hofman, A; Ikram, M A; Tiemeier, H W; Uitterlinden, A G; van Rooij, F J A; Barroso, I; Johansson, I; Xue, L; Kaakinen, M; Milani, L; Power, C; Snieder, H; Stolk, R P; Baumeister, S E; Biffar, R; Gu, F; Bastardot, F; Kutalik, Z; Jacobs, D R; Forouhi, N G; Mihailov, E; Lind, L; Lindgren, C; Michaëlsson, K; Morris, A; Jensen, M; Khaw, K-T; Luben, R N; Wang, J J; Männistö, S; Perälä, M-M; Kähönen, M; Lehtimäki, T; Viikari, J; Mozaffarian, D; Mukamal, K; Psaty, B M; Döring, A; Heath, A C; Montgomery, G W; Dahmen, N; Carithers, T; Tucker, K L; Ferrucci, L; Boyd, H A; Melbye, M; Treur, J L; Mellström, D; Hottenga, J J; Prokopenko, I; Tönjes, A; Deloukas, P; Kanoni, S; Lorentzon, M; Houston, D K; Liu, Y; Danesh, J; Rasheed, A; Mason, M A; Zonderman, A B; Franke, L; Kristal, B S; Karjalainen, J; Reed, D R; Westra, H-J; Evans, M K; Saleheen, D; Harris, T B; Dedoussis, G; Curhan, G; Stumvoll, M; Beilby, J; Pasquale, L R; Feenstra, B; Bandinelli, S; Ordovas, J M; Chan, A T; Peters, U; Ohlsson, C; Gieger, C; Martin, N G; Waldenberger, M; Siscovick, D S; Raitakari, O; Eriksson, J G; Mitchell, P; Hunter, D J; Kraft, P; Rimm, E B; Boomsma, D I; Borecki, I B; Loos, R J F; Wareham, N J; Vollenweider, P; Caporaso, N; Grabe, H J; Neuhouser, M L; Wolffenbuttel, B H R; Hu, F B; Hyppönen, E; Järvelin, M-R; Cupples, L A; Franks, P W; Ridker, P M; van Duijn, C M; Heiss, G; Metspalu, A; North, K E; Ingelsson, E; Nettleton, J A; van Dam, R M; Chasman, D I

    2015-05-01

    Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee. PMID:25288136

  11. Association between vitamin D receptor poly(A) polymorphism and breast cancer risk: a meta-analysis.

    PubMed

    Xu, Jinjiang; Li, Hongyu; Gu, Lixue; Zhou, Xiaoping

    2014-01-01

    Vitamin D receptor (VDR) poly(A) is a common genetic polymorphism in the VDR gene, and it has been implicated to be associated with breast cancer risk. However, previous studies on the association reported inconclusive results. We performed this meta-analysis to comprehensively assess the association. Eligible studies were searched in PubMed and EMBASE databases. Odds ratio (OR) and its 95% confidence interval (95% CI) were used for statistical analysis. A total 6,631 cases and 6,718 controls from 11 case-control studies were finally included into the meta-analysis. Meta-analysis of total eligible studies showed that VDR poly(A) polymorphism was not associated with the risk of breast cancer (S versus L: OR = 0.99, 95% CI of 0.90-1.09, P = 0.84; SS versus LL: OR = 0.96, 95% CI of 0.79-1.18, P = 0.70; SS/LS versus LL: OR = 0.96, 95% CI of 0.83-1.12, P = 0.63; SS versus LL/LS: OR = 1.00, 95% CI of 0.91-1.10, P = 0.98). Meta-analysis of studies with high quality also showed that there was no association between VDR poly(A) polymorphism and breast cancer risk. In addition, in the subgroup analysis by ethnicity, no significant association was found among Caucasians. Therefore, the meta-analysis suggests that VDR poly(A) polymorphism is not associated with the risk of breast cancer. Large well-designed studies are necessary to clarify the possible association in Asians. PMID:24037913

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

    PubMed Central

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

    2015-01-01

    Objective Numerous studies have investigated the associations between herpesviruses and chronic periodontitis; however, the results remain controversial. To derive a more precise estimation, a meta-analysis on all available studies was performed to identify the association between herpesviruses and chronic periodontitis. Methods A computerized literature search was conducted in December 2014 to identify eligible case-control studies from the PUBMED and EMBASE databases according to inclusion and exclusion criteria. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were used to assess the association between herpesviruses and risk of chronic periodontitis. A fixed or random effects model was determined based on a heterogeneity test. Sensitivity analysis was conducted to investigate stability and reliability. Publication bias was investigated using the Begg rank correlation test and Egger's funnel plot. Results Ten eligible studies were included to investigate the association between Epstein–Barr virus (EBV) and chronic periodontitis. The results showed that EBV has a significant association with chronic periodontitis compared with periodontally healthy group (OR = 5.74, 95% CI = 2.53–13.00, P<0.001). The association between human cytomegalovirus (HCMV) and chronic periodontitis was analyzed in 10 studies. The pooled result showed that HCMV also has a significant association with chronic periodontitis (OR = 3.59, 95% CI = 1.41–9.16, P = 0.007). Similar results were found in the sensitivity analyses. No significant publication bias was observed. Two eligible studies were included to investigate the association between herpes simplex virus (HSV) and chronic periodontitis risk. The association between HSV and chronic periodontitis was inconclusive (OR = 2.81 95% CI = 0.95–8.27, P = 0.06). Only one included study investigated the association between human herpesvirus 7 (HHV-7) and chronic periodontitis risk (OR = 1.00, 95% CI = 0

  13. Attitudes, Motivation, and Second Language Learning: A Meta-Analysis of Studies Conducted by Gardner and Associates.

    ERIC Educational Resources Information Center

    Masgoret, Anne-Marie; Gardner, Robert C.

    2003-01-01

    Examined the magnitude of the contributions that motivation and attitudes make to achievement in the second language in he research conducted by Gardner and associates. Meta-analysis indicates the relationship of second language achievement to the five attitude/motivation variables from Gardner's socioeductional model. (Author/VWL)

  14. The Association between Leptin Level and Breast Cancer: A Meta-Analysis

    PubMed Central

    Guo, Weiheng; Shao, Liang; Liu, Yi; Wang, Liqin

    2013-01-01

    Background Contradictory results have been reported regarding the association between leptin level and breast cancer. Therefore, a meta-analysis was performed to investigate this issue. Methods Published literature from PubMed and the Chinese National Knowledge Infrastructure (CNKI) Database was retrieved. This study was performed based on different cases and control groups. The combined effect () with 95% confidence interval (CI) was calculated using fixed-effects or random-effects model analysis. Results Overall, the mean serum leptin level of case groups was significantly higher than that of control groups. A) For 9 studies comparing breast cancer cases and healthy controls the combined effect was 0.58 with 95% CI (0.48, 0.68). B) For 4 studies comparing premenopausal breast cancer cases and healthy controls the was 0.32 (0.12, 0.52). C) For 5 studies comparing postmenopausal cases and healthy controls the was 0.65 (0.46, 0.84). D) For 4 studies comparing breast cancer cases and breast benign controls the was 0.38 (0.17, 0.59). E) For 2 studies comparing premenopausal breast cancer cases and breast benign controls the was 0.33 (-0.25, 0.91). F) For 6 studies comparing postmenopausal breast cancer cases and breast benign controls the was 0.39 (0.19, 0.60). G) For 4 studies comparing lymph node metastasis positive cases and negative controls the was 0.72 (0.45, 1.00). H) For 3 studies comparing breast benign cases and healthy controls the was 0.71 (0.41, 1.01). Conclusion This meta-analysis suggests that leptin level plays a role in breast cancer and has potential for development as a diagnostic tool. PMID:23826274

  15. Association between Apolipoprotein C-III Gene Polymorphisms and Coronary Heart Disease: A Meta-analysis

    PubMed Central

    Zhang, Jing-Zhan; Xie, Xiang; Ma, Yi-Tong; Zheng, Ying-Ying; Yang, Yi-Ning; Li, Xiao-Mei; Fu, Zhen-Yan; Dai, Chuan-Fang; Zhang, Ming-Ming; Yin, Guo-Ting; Liu, Fen; Chen, Bang-Dang; Gai, Min-Tao

    2016-01-01

    Polymorphisms in the apolipoprotein C-III (APOC3) gene have been reported to be associated with coronary heart disease (CHD), but the data so far have been conflicting. To derive a more precise estimation of these associations, we performed a meta-analysis to investigate the three main polymorphisms (SstI, T-455C, C-482T) of APOC3 in all published studies. Databases including PubMed, Web of Science, Wanfang, SinoMed and CNKI were systematically searched. The association was assessed using odds ratios (ORs) with 95% confidence intervals (CIs). The statistical analysis was performed using Review Manager 5.3.3 and Stata 12.0. A total of 31 studies have been identified. The pooled odds ratio (OR) for the association between the APOC3 gene polymorphisms and CHD and its corresponding 95% confidence interval (95% CI) were evaluated by random or fixed effect models. A statistical association between APOC3 SstI polymorphism and CHD susceptibility was observed under an allelic contrast model (P= 0.003, OR = 1.14, 95% CI = 1.05-1.24), dominant genetic model (P= 0.01, OR = 1.14, 95% CI = 1.03-1.26), and recessive genetic model (P= 0.02, OR = 1.35, 95% CI = 1.06-1.71), respectively. A significant association between the APOC3 T-455C polymorphism and CHD was also detected under an allelic contrast (P < 0.0001, OR = 1.19, 95% CI = 1.10-1.29), dominant genetic model (P= 0.0003, OR = 1.24, 95% CI = 1.11-1.39) and recessive genetic model (P= 0.04, OR = 1.30, 95% CI = 1.01-1.67). No significant association between the APOC3 C-482T polymorphism and CHD was found under an allelic model (P= 0.94, OR = 1.00, 95% CI = 0.93-1.08), dominant genetic model (P= 0.20, OR = 1.07, 95% CI = 0.97-1.18) or recessive genetic model (P= 0.13, OR = 0.90, 95% CI = 0.79-1.03). This meta-analysis revealed that the APOC3 SstI and T-455C polymorphisms significantly increase CHD susceptibility. No significant association was observed between the APOC3 C-482T polymorphism and CHD susceptibility. PMID:26816662

  16. Association between ATM polymorphisms and cancer risk: a meta-analysis.

    PubMed

    Shen, Li; Yin, Zhi-Hua; Wan, Yan; Zhang, Yue; Li, Kun; Zhou, Bao-Sen

    2012-05-01

    To date, epidemiological studies have assessed the association between Ataxia-telangiectasia mutated (ATM) gene polymorphisms and cancer risk, including lung cancer, breast cancer, glioma and pancreatic cancer. However, the results of these studies remain controversial. We aimed to examine the associations between two SNPs (rs664143 and rs664677) and cancer risk by conducting a meta-analysis of case-control studies. A total of 12 publications were included in this meta-analysis, 8 for rs664143 and 7 for rs664677. Overall, rs664143 heterozygote carriers turned out to be associated with cancer risk (OR = 1.18, 95% CI 1.02-1.36). In the subgroup analysis by cancer type, we observed that the ATM rs664143 polymorphism was significantly associated with lung cancer risk (GA vs. GG: OR = 1.48, 95% CI 1.18-1.85, AA vs. GG: OR = 1.51, 95% CI 1.18-1.93) and rs664677 polymorphism was associated with decreased lung cancr risk and increased breast cancer risk (for lung cancer: TC vs. TT: OR = 0.76, 95% CI 0.62-0.92, CC vs. TT: OR = 0.80, 95% CI 0.64-0.99 and for breast cancer: TC vs. TT: OR = 1.42, 95% CI 1.17-1.73, CC vs. TT: OR = 1.51, 95% CI 1.21-1.87). In the subgroup analysis by region, we also observed that individuals with ATM rs664143 GA or AA genotype had an obvious increased cancer risk among Asian people (GA vs. GG: OR = 1.40, 95% CI 1.20-1.63, AA vs. GG: OR = 1.37, 95% CI 1.16-1.62). In conclusion, ATM rs664143 polymorphism was associated with cancer susceptibility. ATM rs664143 polymorphism was significantly associated with lung cancer risk. ATM rs664677 polymorphism was associated with decreased lung cancer risk as well as increased breast cancer risk. PMID:22203481

  17. The Association between Telomere Length and Cancer Prognosis: Evidence from a Meta-Analysis

    PubMed Central

    Li, Lu; Zhou, Ying; Wang, Chao; Hou, Shuxun

    2015-01-01

    Background Telomeres are essential for chromosomal integrity and stability. Shortened telomere length (TL) has been associated with risk of cancers and aging-related diseases. Several studies have explored associations between TL and cancer prognosis, but the results are conflicting. Methods Prospective studies on the relationship between TL and cancer survival were identified by a search of PubMed up to May 25, 2015. There were no restrictions on the cancer type or DNA source. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis approaches were conducted to determine pooled relative risks and 95% confidence intervals. Results Thirty-three articles containing forty-five independent studies were ultimately involved in our meta-analysis, of which twenty-seven were about overall cancer survival and eighteen were about cancer progression. Short TL was associated with increased cancer mortality risk (RR = 1.30, 95%CI: 1.06–1.59) and poor cancer progression (RR = 1.44, 95%CI: 1.10–1.88), both with high levels of heterogeneity (I2 = 83.5%, P = 0.012for overall survival and I2 = 75.4%, P = 0.008 for progression). TL was an independent predictor of overall cancer survival and progression in chronic lymphocytic leukemia. Besides, short telomeres were also associated with increased colorectal cancer mortality and decreased overall survival of esophageal cancer, but not in other cancers. Cancer progression was associated with TL in Asian and America populations and short TL predicted poor cancer survival in older populations. Compared with tumor tissue cells, TL in blood lymphocyte cells was better for prediction. In addition, the associations remained significant when restricted to studies with adjustments for age, with larger sample sizes, measuring TL using southern blotting or estimating risk effects by hazard ratios. Conclusion Short TL demonstrated a significant association with poor cancer survival, suggesting the

  18. Association between the MYO9B polymorphisms and celiac disease risk: a meta-analysis

    PubMed Central

    Liao, Ning; Chen, Min-Li; Zhao, Hua; Xie, Zheng-Fu

    2015-01-01

    Background: There is no consensus regarding the association between polymorphisms in the myosin IXB (MYO9B) gene and celiac disease (CD) risk. In this study, we performed a meta-analysis to evaluate genetic variants in MYO9B with CD. Methods: Four MYO9B polymorphisms (rs1545620, rs1457092, rs2305767 and rs2305764) were assessed. A literature search was conducted using PubMed, Scopus, and Web of Science databases until June 2015. Odds ratio (OR) and 95% confidence interval (CI) were used to investigate the strength of the association under dominant, recessive, homozygote and allelic comparison models. Results: Seven case-control studies with a total of 1965 CD patients and 4894 controls were included in this meta-analysis. The results showed that rs1545620 was associated with CD risk in Europeans in dominant (OR=1.31, 95% CI: 1.10-1.58, Pz=0.003), recessive (OR=1.36, 95% CI: 1.08-1.72, Pz=0.009), homozygote (OR=1.55, 95% CI: 1.20-2.01, Pz=0.001), and allelic comparison models (OR=1.24, 95% CI: 1.10-1.40, Pz=0.001), whereas in a Latin American group there were significant associations of CD with rs1457092 in dominant (OR=15.30, 95% CI: 3.51-66.67, Pz<0.001), homozygote (OR=16.55, 95% CI: 3.62-75.65, Pz<0.001), and allelic comparison models (OR=1.95, 95% CI: 1.31-2.91, Pz=0.001), and rs2305767 in dominant (OR=5.35, 95% CI: 2.42-11.86, Pz<0.001) and allelic comparison models (OR=1.65, 95% CI: 1.11-2.45, Pz=0.013). There was no association between rs2305764 and CD risk in either Europeans or the Latin American group. Conclusion: rs1545620 is associated with CD risk in Europeans, whereas rs1457092 and rs2305767 are associated with CD risk in a Latin American group. PMID:26628973

  19. Methods for association analysis and meta-analysis of rare variants in families.

    PubMed

    Feng, Shuang; Pistis, Giorgio; Zhang, He; Zawistowski, Matthew; Mulas, Antonella; Zoledziewska, Magdalena; Holmen, Oddgeir L; Busonero, Fabio; Sanna, Serena; Hveem, Kristian; Willer, Cristen; Cucca, Francesco; Liu, Dajiang J; Abecasis, Gonçalo R

    2015-05-01

    Advances in exome sequencing and the development of exome genotyping arrays are enabling explorations of association between rare coding variants and complex traits. To ensure power for these rare variant analyses, a variety of association tests that group variants by gene or functional unit have been proposed. Here, we extend these tests to family-based studies. We develop family-based burden tests, variable frequency threshold tests and sequence kernel association tests. Through simulations, we compare the performance of different tests. We describe situations where family-based studies provide greater power than studies of unrelated individuals to detect rare variants associated with moderate to large changes in trait values. Broadly speaking, we find that when sample sizes are limited and only a modest fraction of all trait-associated variants can be identified, family samples are more powerful. Finally, we illustrate our approach by analyzing the relationship between coding variants and levels of high-density lipoprotein (HDL) cholesterol in 11,556 individuals from the HUNT and SardiNIA studies, demonstrating association for coding variants in the APOC3, CETP, LIPC, LIPG, and LPL genes and illustrating the value of family samples, meta-analysis, and gene-level tests. Our methods are implemented in freely available C++ code. PMID:25740221

  20. Methods for Association Analysis and Meta-Analysis of Rare Variants in Families

    PubMed Central

    Feng, Shuang; Pistis, Giorgio; Zhang, He; Zawistowski, Matthew; Mulas, Antonella; Zoledziewska, Magdalena; Holmen, Oddgeir L.; Busonero, Fabio; Sanna, Serena; Hveem, Kristian; Willer, Cristen; Cucca, Francesco; Liu, Dajiang J.; Abecasis, Gonçalo R.

    2015-01-01

    Advances in exome sequencing and the development of exome genotyping arrays are enabling explorations of association between rare coding variants and complex traits. To ensure power for these rare variant analyses, a variety of association tests that group variants by gene or functional unit have been proposed. Here, we extend these tests to family-based studies. We develop family-based burden tests, variable frequency threshold tests and sequence kernel association tests (SKAT). Through simulations we compare the performance of different tests. We describe situations where family-based studies provide greater power than studies of unrelated individuals to detect rare variants associated with moderate to large changes in trait values. Broadly speaking, we find that when sample sizes are limited and only a modest fraction of all trait-associated variants can be identified, family samples are more powerful. Finally, we illustrate our approach by analyzing the relationship between coding variants and HDL in 11,556 individuals from the HUNT and SardiNIA studies, demonstrating association for coding variants in the APOC3, CETP, LIPC, LIPG, and LPL genes and illustrating the value of family samples, meta-analysis and gene-level tests. Our methods are implemented in freely available C++ code. PMID:25740221

  1. Exploring the Major Sources and Extent of Heterogeneity in a Genome-Wide Association Meta-Analysis.

    PubMed

    Pei, Yu-Fang; Tian, Qing; Zhang, Lei; Deng, Hong-Wen

    2016-03-01

    Genome-wide association (GWA) meta-analysis has become a popular approach for discovering genetic variants responsible for complex diseases. The between-study heterogeneity effect is a severe issue that may complicate the interpretation of results. Aiming to improve the interpretation of meta-analysis results, we empirically explored the extent and source of heterogeneity effect. We analyzed a previously reported GWA meta-analysis of obesity, in which over 21,000 subjects from seven individual samples were meta-analyzed. We first evaluated the extent and distribution of heterogeneity across the entire genome. We then studied the effects of several potentially confounding factors, including age, ethnicity, gender composition, study type, and genotype imputation on heterogeneity with a random-effects meta-regression model. Of the total 4,325,550 SNPs being tested, heterogeneity was moderate to very large for 25.4% of the total SNPs. Heterogeneity was more severe in SNPs with stronger association signals. Ethnicity, average age, and genotype imputation accuracy had significant effects on the heterogeneity. Exploring the effects of ethnicity can provide clues to the potential ethnic-specific effects for two loci known to affect obesity, MC4R, and MTCH2. Our analysis can help to clarify understanding of the obesity mechanism and may provide guidance for an effective design of future GWA meta-analysis. PMID:26686198

  2. Meta-analysis of the association between short-term exposure to ambient ozone and respiratory hospital admissions

    NASA Astrophysics Data System (ADS)

    Ji, Meng; Cohan, Daniel S.; Bell, Michelle L.

    2011-04-01

    Ozone is associated with health impacts including respiratory outcomes; however, results differ across studies. Meta-analysis is an increasingly important approach to synthesizing evidence across studies. We conducted meta-analysis of short-term ozone exposure and respiratory hospitalizations to evaluate variation across studies and explore some of the challenges in meta-analysis. We identified 136 estimates from 96 studies and investigated how estimates differed by age, ozone metric, season, lag, region, disease category, and hospitalization type. Overall results indicate associations between ozone and various kinds of respiratory hospitalizations; however, study characteristics affected risk estimates. Estimates were similar, but higher, for the elderly compared to all ages and for previous day exposure compared to same day exposure. Comparison across studies was hindered by variation in definitions of disease categories, as some (e.g., asthma) were identified through >= 3 different sets of ICD codes. Although not all analyses exhibited evidence of publication bias, adjustment for publication bias generally lowered overall estimates. Emergency hospitalizations for total respiratory disease increased by 4.47% (95% interval: 2.48, 6.50%) per 10 ppb 24 h ozone among the elderly without adjustment for publication bias and 2.97% (1.05, 4.94%) with adjustment. Comparison of multi-city study results and meta-analysis based on single-city studies further suggested publication bias.

  3. Association of Hemostatic Markers with Atrial Fibrillation: A Meta-Analysis and Meta-Regression

    PubMed Central

    Xiang, Ying; Wu, Long; Xu, Bin; Zhang, Yao; Ma, Xiangyu; Li, Yafei; Song, Zhiyuan; Zhong, Li

    2015-01-01

    Background There is growing evidence that indicates the presence of a prothrombotic state in atrial fibrillation (AF). However, the role of hemostatic markers in AF remains inconclusive. Methods We conducted a meta-analysis of observational studies to evaluate the association between hemostatic markers and AF. A meta-regression was performed to explore potential sources of heterogeneity. Results A total of 59 studies met our inclusion criteria for the meta-analysis. For platelet activation, increased circulating platelet factor-4, β-thromboglobulin (BTG) and P-selectin were significantly higher in AF cases compared with controls (standardized mean difference [SMD][95% confidence interval (CI)]: 1.72[0.96–2.49], 1.61[1.03–2.19] and 0.50[0.23–0.77], respectively). For coagulation activation, increased levels of plasma D-dimer, fibrinogen, thrombin-antithrombin, prothrombin fragment 1+2, and antithrombin-III were significantly associated with AF (SMD[95% CI]: 1.82[1.38–2.26], 0.72[0.55–0.89], 0.42[0.13–0.72], 1.00 [0.00–1.99] and 1.38[0.16–2.60], respectively). For fibrinolytic function, tissue-type plasminogen activator and plasminogen activator inhibitor-1 were significantly increased in AF cases compared with controls (SMD[95% CI]: 0.86[0.04–1.67] and 0.87[0.28–1.47], respectively) but the associations became nonsignificant after performing subgroup analysis by anticoagulants treatment status. For endothelial function, increased von Willebrand factor was significantly associated with AF (SMD, 0.79; 95% CI, 0.60–0.99); however, no association was observed for soluble thrombomodulin (SMD, 0.60; 95% CI, -0.13–1.33). Conclusions Increased circulating hemostatic factors (PF-4, BTG, P-selectin, D-dimer, fibrinogen, TAT, F1+2, AT- III, and vWf) are significantly associated with AF. Future research is necessary to elucidate the precise mechanism of the prothrombotic state and how hemostatic markers promote thromboembolism in AF. PMID:25884835

  4. Meta-analysis of New Genome-wide Association Studies of Colorectal Cancer Risk

    PubMed Central

    Peters, Ulrike; Hutter, Carolyn M.; Hsu, Li; Schumacher, Fredrick R.; Conti, David V.; Carlson, Christopher S.; Edlund, Christopher K.; Haile, Robert W.; Gallinger, Steven; Zanke, Brent W.; Lemire, Mathieu; Rangrej, Jagadish; Vijayaraghavan, Raakhee; Chan, Andrew T.; Hazra, Aditi; Hunter, David J.; Ma, Jing; Fuchs, Charles S.; Giovannucci, Edward L.; Kraft, Peter; Liu, Yan; Chen, Lin; Jiao, Shuo; Makar, Karen W.; Taverna, Darin; Gruber, Stephen B.; Rennert, Gad; Moreno, Victor; Ulrich, Cornelia M.; Woods, Michael O.; Green, Roger C.; Parfrey, Patrick S.; Prentice, Ross L.; Kooperberg, Charles; Jackson, Rebecca D.; LaCroix, Andrea Z.; Caan, Bette J.; Hayes, Richard B.; Berndt, Sonja I.; Chanock, Stephen J.; Schoen, Robert E.; Chang-Claude, Jenny; Hoffmeister, Michael; Brenner, Hermann; Frank, Bernd; Bézieau, Stéphane; Küry, Sébastien; Slattery, Martha L.; Hopper, John L.; Jenkins, Mark A.; Le Marchand, Loic; Lindor, Noralane M.; Newcomb, Polly A.; Seminara, Daniela; Hudson, Thomas J.; Duggan, David J.; Potter, John D.; Casey, Graham

    2011-01-01

    Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow-up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for genome-wide association studies (GWAS) of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using 10 independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured 10 SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p-value range: 0.02 to 1.8 × 10−8). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p<0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p-value 0.03; combined p-value 7.3 × 10−5). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant

  5. Meta-analysis of loci associated with age at natural menopause in African-American women

    PubMed Central

    Chen, Christina T.L.; Liu, Ching-Ti; Chen, Gary K.; Andrews, Jeanette S.; Arnold, Alice M.; Dreyfus, Jill; Franceschini, Nora; Garcia, Melissa E.; Kerr, Kathleen F.; Li, Guo; Lohman, Kurt K.; Musani, Solomon K.; Nalls, Michael A.; Raffel, Leslie J.; Smith, Jennifer; Ambrosone, Christine B.; Bandera, Elisa V.; Bernstein, Leslie; Britton, Angela; Brzyski, Robert G.; Cappola, Anne; Carlson, Christopher S.; Couper, David; Deming, Sandra L.; Goodarzi, Mark O.; Heiss, Gerardo; John, Esther M.; Lu, Xiaoning; Le Marchand, Loic; Marciante, Kristin; Mcknight, Barbara; Millikan, Robert; Nock, Nora L.; Olshan, Andrew F.; Press, Michael F.; Vaiyda, Dhananjay; Woods, Nancy F.; Taylor, Herman A.; Zhao, Wei; Zheng, Wei; Evans, Michele K.; Harris, Tamara B.; Henderson, Brian E.; Kardia, Sharon L.R.; Kooperberg, Charles; Liu, Yongmei; Mosley, Thomas H.; Psaty, Bruce; Wellons, Melissa; Windham, Beverly G.; Zonderman, Alan B.; Cupples, L. Adrienne; Demerath, Ellen W.; Haiman, Christopher; Murabito, Joanne M.; Rajkovic, Aleksandar

    2014-01-01

    Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA. PMID:24493794

  6. Metabolic Syndrome Is Associated with Increased Breast Cancer Risk: A Systematic Review with Meta-Analysis

    PubMed Central

    Bhandari, Ruchi; Kelley, George A.; Hartley, Tara A.; Rockett, Ian R. H.

    2014-01-01

    Background. Although individual metabolic risk factors are reported to be associated with breast cancer risk, controversy surrounds risk of breast cancer from metabolic syndrome (MS). We report the first systematic review and meta-analysis of the association between MS and breast cancer risk in all adult females. Methods. Studies were retrieved by searching four electronic reference databases [PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and ProQuest through June 30, 2012] and cross-referencing retrieved articles. Eligible for inclusion were longitudinal studies reporting associations between MS and breast cancer risk among females aged 18 years and older. Relative risks and 95% confidence intervals were calculated for each study and pooled using random-effects models. Publication bias was assessed quantitatively (Trim and Fill) and qualitatively (funnel plots). Heterogeneity was examined using Q and I2 statistics. Results. Representing nine independent cohorts and 97,277 adult females, eight studies met the inclusion criteria. A modest, positive association was observed between MS and breast cancer risk (RR: 1.47, 95% CI, 1.15–1.87; z = 3.13; p = 0.002; Q = 26.28, p = 0.001; I2 = 69.55%). No publication bias was observed. Conclusions. MS is associated with increased breast cancer risk in adult women. PMID:25653879

  7. Association between two CHRNA3 variants and susceptibility of lung cancer: a meta-analysis.

    PubMed

    Qu, Xiao; Wang, Kai; Dong, Wei; Shen, Hongchang; Wang, Ying; Liu, Qi; Du, Jiajun

    2016-01-01

    Genome-wide association studies (GWAS) have identified two CHRNA3 polymorphisms (rs578776 and rs938682) associated with lung cancer risk. Furthermore, these polymorphisms were investigated and genotyped by PCR analysis. All eligible case-control studies published up to Mar 1st 2015 were identified by searching Pubmed and Embase database. Negative association between rs578776-T allele and risk of lung cancer was obtained without obvious heterogeneity (OR: 0.83, 95% CI: 0.79-0.86; p = 0.898 for Q test). Rs938682-C allele carriers had a 12% to 28% decreased risk. Genotype model analysis showed results of dominant model for rs578776 (OR with 95% CI: 0.839(0.718-0.981)), dominant model for rs938682 (OR with 95% CI: 0.778(0.663-0.912)) and homozygous model for rs938682 (OR with 95% CI: 0.767(0.708-0.831)) were statistically significant. Subgroup analysis indicated rs578776-T variant had protective effect in Smokers, Caucasians, two histology subgroups, and two match subgroups. Meanwhile, rs938682-C allele was associated with decreased risk in Smokers, Caucasians, Lung cancer, and two match subgroups. Meta-regression suggested ethnicity might be the major source of heterogeneity in allele model and homozygous model for rs938682. Moreover, smoking status might contribute to part of heterogeneity under allele model. In summary, this meta-analysis suggested both rs578776 and rs938682 were significantly associated with the susceptibility of lung cancer. PMID:26831765

  8. Associations between Intimate Partner Violence and Termination of Pregnancy: A Systematic Review and Meta-Analysis

    PubMed Central

    Hall, Megan; Chappell, Lucy C.; Parnell, Bethany L.; Seed, Paul T.; Bewley, Susan

    2014-01-01

    Background Intimate partner violence (IPV) and termination of pregnancy (TOP) are global health concerns, but their interaction is undetermined. The aim of this study was to determine whether there is an association between IPV and TOP. Methods and Findings A systematic review based on a search of Medline, Embase, PsycINFO, and Ovid Maternity and Infant Care from each database's inception to 21 September 2013 for peer-reviewed articles of any design and language found 74 studies regarding women who had undergone TOP and had experienced at least one domain (physical, sexual, or emotional) of IPV. Prevalence of IPV and association between IPV and TOP were meta-analysed. Sample sizes ranged from eight to 33,385 participants. Worldwide, rates of IPV in the preceding year in women undergoing TOP ranged from 2.5% to 30%. Lifetime prevalence by meta-analysis was shown to be 24.9% (95% CI 19.9% to 30.6%); heterogeneity was high (I2>90%), and variation was not explained by study design, quality, or size, or country gross national income per capita. IPV, including history of rape, sexual assault, contraceptive sabotage, and coerced decision-making, was associated with TOP, and with repeat TOPs. By meta-analysis, partner not knowing about the TOP was shown to be significantly associated with IPV (pooled odds ratio 2.97, 95% CI 2.39 to 3.69). Women in violent relationships were more likely to have concealed the TOP from their partner than those who were not. Demographic factors including age, ethnicity, education, marital status, income, employment, and drug and alcohol use showed no strong or consistent mediating effect. Few long-term outcomes were studied. Women welcomed the opportunity to disclose IPV and be offered help. Limitations include study heterogeneity, potential underreporting of both IPV and TOP in primary data sources, and inherent difficulties in validation. Conclusions IPV is associated with TOP. Novel public health approaches are required to prevent IPV. TOP

  9. Association of programmed death-1 gene polymorphism rs2227981 with tumor: evidence from a meta analysis

    PubMed Central

    Mamat, Umarjan; Arkinjan, Muyassar

    2015-01-01

    To investigate the association of programmed death-1 gene polymorphism rs2227981 with tumor risk. The PubMed, Medline, Ovid Medline, EMBASE, Web of Knowledge were searched. Meta-analyses were conducted using RevMan 5.2.2 software. Total six researches involving in a total of 1427 tumor patients and 1811 healthy control people were included into this meta analysis. There was no association of PD-1 gene polymorphism with total tumor risk under four genetic models. (CT+TT vs CC, OR=1.09, 95% CI=0.80-1.49, P=0.59; CT+CC vs TT, OR=0.93, 95% CI=0.52-1.66, P=0.61; TT vs CC, OR=0.99, 95% CI=0.57-1.72, P=0.97; CT vs CC, OR=1.16, 95% CI=0.80-1.70, P=0.43). The sub-group analysis shown there were a significantly difference on association of PD-1 gene polymorphism with digestive system tumor risk between tumor patients and healthy control people, except recessive model. (CT+TT vs CC, OR=1.57, 95% CI=1.20-2.07, P=0.001; TT vs CC, OR=1.67, 95% CI=1.12-2.49, P=0.01; CT vs CC, OR=1.51, 95% CI=1.13-2.01, P=0.005). Moreover, the meta analysis results shown that there were association of PD-1 gene polymorphism with tumor risk under two models for the tumor specific occurring only in women. (CT+TT vs CC, OR=0.80, 95% CI=0.67-0.95, P=0.01; TT vs CC, OR=0.61, 95% CI=0.44-0.83, P=0.002). This study suggests that PD-1 gene polymorphism rs2227981 is associated with specific tumor types, including digestive system tumor and tumor specific occurring in woman. PMID:26550254

  10. Polymorphism in IGFBP3 gene is associated with prostate cancer risk: an updated meta-analysis

    PubMed Central

    Qie, Yunkai; Nian, Xuewu; Liu, Xuesen; Hu, Hailong; Zhang, Changwen; Xie, Linguo; Han, Ruifa; Wu, Changli; Xu, Yong

    2016-01-01

    Objective Insulin-like growth factor-binding protein-3 (IGFBP3) is the major protein that binds with insulin-like growth factor-1 (IGF-1) and is considered to be involved in the development and progression of various cancers. We aimed to examine the association between prostate cancer (PCa) and the IGFBP3 gene-202A/C polymorphism. Methods A comprehensive search within PubMed, EMBASE, and Cochrane Library was conducted to identify all case–control studies up to October 30, 2015, for a meta-analysis. Pooled odds ratios (ORs) and the 95% confidence intervals (CIs) were calculated using the fixed or random effects model. Results Eighteen studies including 10,538 cases and 10,078 controls were identified. Overall, the CC genotype of IGFBP3-202A/C polymorphism was associated with increased risk of PCa in homozygote comparison (CC vs AA − OR =1.16, 95% CI: 1.08–1.25) and in recessive model (CC vs AA+AC − OR =1.11, 95% CI: 1.04–1.17). In dominant model, the CC/AC genotypes also implicated an increased risk of PCa (CC+AC vs AA − OR =1.11, 95% CI: 1.05–1.19). The C allele of IGFBP3-202A/C polymorphism was the risk allele for PCa relative to the A allele (OR =1.09, 95% CI: 1.05–1.14). Further stratification analysis revealed that the association between –202A/C polymorphism and PCa risk among Caucasians, but not in other ethnicities, was statistically significant (recessive model, OR =1.10, 95% CI: 1.02–1.19). In addition, the IGFBP3-202A/C polymorphism was associated with PCa risk in both population-based and hospital-based studies in homozygote comparison, recessive model, and allele model. Conclusion Our meta-analysis indicates that the IGFBP3-202A/C polymorphism is associated with the risk of PCa, particularly in Caucasians, with the C allele being the risk allele for PCa. PMID:27462171

  11. Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies

    PubMed Central

    2014-01-01

    Summary Background The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilepsy and focal epilepsy). Methods We combined genome-wide association data from 12 cohorts of individuals with epilepsy and controls from population-based datasets. Controls were ethnically matched with cases. We phenotyped individuals with epilepsy into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. After standardised filtering for quality control and imputation to account for different genotyping platforms across sites, investigators at each site conducted a linear mixed-model association analysis for each dataset. Combining summary statistics, we conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy. We set the genome-wide significance threshold at p<1·66 × 10−8. Findings We included 8696 cases and 26 157 controls in our analysis. Meta-analysis of the all-epilepsy cohort identified loci at 2q24.3 (p=8·71 × 10−10), implicating SCN1A, and at 4p15.1 (p=5·44 × 10−9), harbouring PCDH7, which encodes a protocadherin molecule not previously implicated in epilepsy. For the cohort of genetic generalised epilepsy, we noted a single signal at 2p16.1 (p=9·99 × 10−9), implicating VRK2 or FANCL. No single nucleotide polymorphism achieved genome-wide significance for focal epilepsy. Interpretation This meta-analysis describes a new locus not previously implicated in epilepsy and provides further evidence about the genetic architecture of these disorders, with the

  12. Global Association of Cold Spells and Adverse Health Effects: A Systematic Review and Meta-Analysis

    PubMed Central

    Ryti, Niilo R.I.; Guo, Yuming; Jaakkola, Jouni J.K.

    2015-01-01

    Background There is substantial evidence that mortality increases in low temperatures. Less is known about the role of prolonged cold periods denoted as cold spells. Objective We conducted the first systematic review and meta-analysis to summarize the evidence on the adverse health effects of cold spells in varying climates. Data sources and extraction Four databases (Ovid Medline, PubMed, Scopus, Web of Science) were searched for all years and languages available. “Cold spell” was defined as an event below a temperature threshold lasting for a minimum duration of 2 days. Of 1,527 identified articles, 26 satisfied our eligibility criteria for the systematic review, and 9 were eligible for meta-analyses. The articles were grouped by the three main study questions into Overall-effect Group, Added-effect Group, and Temperature-change-effect Group. Data synthesis Based on random-effects models in the meta-analyses, cold spells were associated with increased mortality from all or all nonaccidental causes (summary rate ratio = 1.10; 95% CI: 1.04, 1.17 based on 9 estimates from five studies), cardiovascular diseases (1.11; 95% CI: 1.03, 1.19; 12 estimates from eight studies), and respiratory diseases (1.21; 95% CI: 0.97, 1.51; 8 estimates from four studies). Estimated associations were stronger for people ≥ 65 years of age (1.06; 95% CI: 1.00, 1.12) than for people 0–64 years of age (1.01; 95% CI: 1.00, 1.03). Study-specific effect estimates from a limited number of studies suggested an increased morbidity related to cold spells, but it was not possible to quantitatively summarize the evidence. Conclusions Cold spells are associated with increased mortality rates in populations around the world. The body of evidence suggests that cold spells also have other adverse health effects. There was substantial heterogeneity among the studies, which should be taken into account in the interpretation of the results. Citation Ryti NR, Guo Y, Jaakkola JJ. 2016. Global

  13. Incidence of Cancer in ANCA-Associated Vasculitis: A Meta-Analysis of Observational Studies

    PubMed Central

    Shang, Weifeng; Ning, Yong; Xu, Xiu; Li, Menglan; Guo, Shuiming; Han, Min; Zeng, Rui; Ge, Shuwang; Xu, Gang

    2015-01-01

    Objective The purpose of this paper is to examine cancer incidence in patients with ANCA-associated vasculitis (AASV) derived from population-based cohort studies by means of meta-analysis. Methods Relevant electronic databases were searched for studies characterizing the associated risk of overall malignancy in patients with AASV. Standardized incidence rates (SIRs) with 95% confidence intervals (CIs) were used to evaluate the strength of association. We tested for publication bias and heterogeneity and stratified for site-specific cancers. Results Six studies (n = 2,578) were eventually identified, of which six provided the SIR for overall malignancy, five reported the SIR for non-melanoma skin cancer (NMSC), four for leukemia, five for bladder cancer, three for lymphoma, three for liver cancer, four for lung cancer, three for kidney cancer, four for prostate cancer, four for colon cancer and four for breast cancer. Overall, the pooled SIR of cancer in AASV patients was 1.74 (95%CI = 1.37–2.21), with moderate heterogeneity among these studies (I2 = 65.8%, P = 0.012). In sub-analyses for site-specific cancers, NMSC, leukemia and bladder cancer were more frequently observed in patients with AASV with SIR of 5.18 (95%CI = 3.47–7.73), 4.89 (95%CI = 2.93–8.16) and 3.84 (95%CI = 2.72–5.42) respectively. There was no significant increase in the risk of kidney cancer (SIR = 2.12, 95%CI = 0.66–6.85), prostate cancer (SIR = 1.45, 95%CI = 0.87–2.42), colon cancer (SIR = 1.26, 95%CI = 0.70–2.27), and breast cancer (SIR = 0.95, 95%CI = 0.50–1.79). Among these site-specific cancers, only NMSC showed moderate heterogeneity (I2 = 55.8%, P = 0.06). No publication bias was found by using the Begg’s test and Egger's test. Conclusions This meta-analysis shows that AASV patients treatment with cyclophosphamide (CYC) are at increased risk of late-occurring malignancies, particularly of the NMSC, leukemia and bladder cancer. However, there is no significant

  14. The association of ACT -17 A/T polymorphism with Alzheimer's disease: a meta-analysis.

    PubMed

    Dou, Chao; Zhang, Jiyuan; Sun, Yang; Zhao, Xin; Wu, Qihan; Ji, Chaoneng; Gu, Shaohua; Xie, Yi; Mao, Yumin

    2013-01-01

    Association studies between Alpha-1-antichymotrypsin (ACT)-17(A > T) polymorphisms and Alzheimer's disease (AD) susceptibility have shown conflicting results. In this investigation, we performed a meta-analysis to assess the purported associations. Subgroup analyses based on ethnicity (Caucasians, East-Asian and American mixed) were also performed including a total of 5,676 AD patients and 5,460 controls for ACT-17. Overall, allele contrast (A vs. T) of ACT -17 polymorphism produced significant results in the worldwide population [P(heterogeneity)=0.01, random-effects (RE) odds ratio (OR) 1.12; 95% CI 1.04-1.21, P=0.003] and in the Caucasian population [P(heterogeneity)=0.03, RE OR1.11 95% CI 1.01-1.24, P=0.04]. Meta-analyses of other genetic contrasts suggested that the A allele carriers are associated with increased susceptibility to AD in variant populations. No significant association was observed in the East-Asian subgroup analysis. In conclusion, ACT-17 variation presents a risk factor for AD in the worldwide population, especially in the Caucasian population. PMID:22272609

  15. Genome-wide association meta-analysis identifies new endometriosis risk loci

    PubMed Central

    Nyholt, Dale R.; Low, Siew-Kee; Anderson, Carl A.; Painter, Jodie N.; Uno, Satoko; Morris, Andrew P.; MacGregor, Stuart; Gordon, Scott D.; Henders, Anjali K.; Martin, Nicholas G.; Attia, John; Holliday, Elizabeth G.; McEvoy, Mark; Scott, Rodney J.; Kennedy, Stephen H.; Treloar, Susan A.; Missmer, Stacey A.; Adachi, Sosuke; Tanaka, Kenichi; Nakamura, Yusuke; Zondervan, Krina T.; Zembutsu, Hitoshi; Montgomery, Grant W.

    2012-01-01

    We conducted a genome-wide association (GWA) meta-analysis of 4,604 endometriosis cases and 9,393 controls of Japanese1 and European2 ancestry. We show that rs12700667 on chromosome 7p15.2, previously found in Europeans, replicates in Japanese (P = 3.6 × 10−3), and confirm association of rs7521902 on 1p36.12 near WNT4. In addition, we establish association of rs13394619 in GREB1 on 2p25.1 and identify a novel locus on 12q22 near VEZT (rs10859871). Excluding European cases with minimal or unknown severity, we identified additional novel loci on 2p14 (rs4141819), 6p22.3 (rs7739264) and 9p21.3 (rs1537377). All seven SNP effects were replicated in an independent cohort and produced P < 5 × 10−8 in a combined analysis. Finally, we found a significant overlap in polygenic risk for endometriosis between the European and Japanese GWA cohorts (P = 8.8 × 10−11), indicating that many weakly associated SNPs represent true endometriosis risk loci and risk prediction and future targeted disease therapy may be transferred across these populations. PMID:23104006

  16. Association Between Six Genetic Polymorphisms and Colorectal Cancer: A Meta-Analysis

    PubMed Central

    Chen, Cheng; Wang, Lingyan; Liao, Qi; Xu, Leiting; Huang, Yi; Zhang, Cheng; Ye, Huadan; Xu, Xuting

    2014-01-01

    Objective: The aim of this study was to determine whether six genetic polymorphisms confer susceptibility to colorectal cancer (CRC). Methods: A systematic search for candidate genes of CRC was performed among several online databases, including PubMed, Embase, Web of Science, the Cochrane Library, CNKI, and Wanfang online libraries. After a comprehensive filtering procedure, we harvested five genes, including MGMT (rs12917 and rs2308321), ADH1B (rs1229984), SOD2 (rs4880), XPC (rs2228001), and PPARG (rs1801282). Using the REVMAN and Stata software, six meta-analyses were conducted for associations between CRC and the just-mentioned genetic variants. Results: A total of 34 comparative studies among 17,289 cases and 54,927 controls were involved in our meta-analyses. Significant association was found between ADH1B rs1229984 polymorphism and CRC (p=0.03, odds ratio [OR]=1.18, 95% confidence interval [CI]=1.01–1.36). We also found significant association between PPARG rs1801282 polymorphism and CRC (p=0.004, OR=1.498, 95% CI=1.139–1.970), and this significant association is specific in Caucasians (p=0.004, OR=1.603, 95% CI=1.165–2.205). Conclusions: The current meta-analysis has established that ADH1B (rs1229984) and PPARG (rs1801282) are two risk variants of CRC. PMID:24552298

  17. Association of COL1A1 polymorphism with high myopia: a Meta-analysis

    PubMed Central

    Jin, Guang-Ming; Zhao, Xiao-Jing; Chen, Ai-Ming; Chen, Yong-Xing; Li, Qin

    2016-01-01

    AIM To investigate the association between collagen type I alpha 1 (COL1A1) gene and high myopia. METHODS In this Meta-analysis, we examined 5 published case-control studies that involved 1942 high myopia cases and 2929 healthy controls to assess the association between the COL1A1 rs2075555 polymorphism and high myopia risk. We calculated the pooled odds ratios (ORs) of COL1A1 rs2075555 polymorphism in high myopia cases vs healthy controls to evaluate the strength of the association. RESULTS Overall, there was no significant difference both in the genotype and allele distributions of COL1A1 rs2075555 polymorphism between high myopia cases and healthy controls: CC vs AA OR=1.10, 95% confidence interval (CI)=0.76-1.58; AC vs AA OR=0.98, 95%CI 0.80-1.20; CC/AC vs AA/OR=1.01, 95%CI 0.84-1.22; CC vs AC/AA OR=1.06, 95%CI=0.93-1.20; C vs A OR=1.06, 95%CI 0.91-1.23). In addition, in the stratified analyses by ethnicity, no significant associations were found in any genetic model both in European and Asia cohorts. CONCLUSION Our results indicate that the COL1A1 rs2075555 polymorphism may not affect susceptibility to high myopia. PMID:27162737

  18. Meta-analysis of genome-wide association from genomic prediction models.

    PubMed

    Bernal Rubio, Y L; Gualdrón Duarte, J L; Bates, R O; Ernst, C W; Nonneman, D; Rohrer, G A; King, A; Shackelford, S D; Wheeler, T L; Cantet, R J C; Steibel, J P

    2016-02-01

    Genome-wide association (GWA) studies based on GBLUP models are a common practice in animal breeding. However, effect sizes of GWA tests are small, requiring larger sample sizes to enhance power of detection of rare variants. Because of difficulties in increasing sample size in animal populations, one alternative is to implement a meta-analysis (MA), combining information and results from independent GWA studies. Although this methodology has been used widely in human genetics, implementation in animal breeding has been limited. Thus, we present methods to implement a MA of GWA, describing the proper approach to compute weights derived from multiple genomic evaluations based on animal-centric GBLUP models. Application to real datasets shows that MA increases power of detection of associations in comparison with population-level GWA, allowing for population structure and heterogeneity of variance components across populations to be accounted for. Another advantage of MA is that it does not require access to genotype data that is required for a joint analysis. Scripts related to the implementation of this approach, which consider the strength of association as well as the sign, are distributed and thus account for heterogeneity in association phase between QTL and SNPs. Thus, MA of GWA is an attractive alternative to summarizing results from multiple genomic studies, avoiding restrictions with genotype data sharing, definition of fixed effects and different scales of measurement of evaluated traits. PMID:26607299

  19. The association between deficient manganese levels and breast cancer: a meta-analysis

    PubMed Central

    Shen, Fei; Cai, Wen-Song; Li, Jiang-Lin; Feng, Zhe; Cao, Jie; Xu, Bo

    2015-01-01

    There are conflicting reports on the correlation between manganese (Mn) levels and breast cancer. The purpose of the present study is to clarify the association between Mn levels and breast cancer using a meta-analysis approach. We searched articles indexed in Pubmed and the Chinese Journal Full-text Database (CJFD) published as of August 2014 that met our predefined criteria. Eleven eligible studies involving 1302 subjects were identified. Overall, pooled analysis indicated that subjects with breast cancer had lower Mn levels than the healthy controls (SMD = -1.51, 95% CI = [-2.47, -0.56]). Further subgroup analysis found a similar pattern in China (SMD = -1.32, 95% CI = [-2.33, -0.32]) and Korea (SMD = -4.08, 95% CI = [-4.63, -3.54]), but not in Turkey (SMD = -0.96, 95% CI = [-3.19, 1.27]). Further subgroup analysis also found a similar pattern in different sample specimens (serum: SMD = -1.24, 95% CI = [-2.31, -0.16]; hair: SMD = -1.99, 95% CI = [-3.91, -0.06]) and different types of Mn measurement (inductively coupled plasma-atomic absorption spectrometry (ICP-AAS): SMD = -1.14, 95% CI = [-2.24, -0.04]; graphite furnace atomic absorption spectroscopy (GFAAS): SMD = -1.94, 95% CI = [-2.38, -1.49]; inductively coupled plasma-atomic emission spectrometry (ICP-AES): SMD = -3.77, 95% CI = [-4.70, -2.85]). No evidence of publication bias was observed. In conclusion, this meta-analysis supports a significant association between deficient Mn levels and breast cancer. However, the subgroup analysis found that there was contradiction regarding races and geography, like China and Turkey. Thus this finding needs further confirmation by trans-regional multicenter, long-term observation in a cohort design to obtain better understanding of causal relationships between Mn levels and breast cancer, through measuring Mn at baseline to investigate whether the highest Mn category versus lowest was associated with breast cancer risk. PMID:26064262

  20. Association between maternal HBsAg carrier status and neonatal adverse outcomes: meta-analysis.

    PubMed

    Luo, Lili; Wu, Jinlin; Qu, Yi; Li, Jiao; Pan, Lingli; Li, Deyuan; Wang, Huiqing; Mu, Dezhi

    2014-09-18

    Abstract Objective: We conducted a meta-analysis to evaluate whether maternal hepatitis B virus (HBV) carrier status increases the risk of neonatal complications. Methods: Publications addressing the association between maternal HBV carrier status and neonatal outcomes were selected from the PubMed, EMBASE, Web of Science, Cochrane Library and China National Knowledge Infrastructure. Publication bias and heterogeneity across studies were evaluated and summary odds ratios, weighted mean difference or standardized mean difference and 95% confidence intervals were calculated and compared between groups. Results: Eighteen studies and 7600 pregnant HBV carriers were selected for analyses. A statistically association with maternal HBV carrier status was demonstrated for premature birth and asphyxia, with no difference found among perinatal mortality, gestational age, small for gestational age, large for gestational age, birth weight, low birth weight, macrosomia, Apgar sore at 1 min, jaundice and congenital anomaly. Heterogeneity across studies was found, and no publication bias was detected. Conclusion: Our analysis suggests that maternal hepatitis B carrier status is significantly associated with premature birth and asphyxia. Large-scale prospective studies are still warranted. PMID:25231370

  1. A Systematic Review and Meta-Analysis on the Association between Hypertension and Tinnitus

    PubMed Central

    Yang, Pan; Ma, Wenjun; Zheng, Yiqing; Yang, Haidi; Lin, Hualiang

    2015-01-01

    Hypertension has been suggested to be one possible risk factor of tinnitus, but the association between hypertension and tinnitus remains uncertain. The authors performed a meta-analysis of the existing studies on the association between hypertension and tinnitus. We performed literature search of studies using SinoMed, CNKI, WanFang, PubMed, Scopus, Web of Science, and Google Scholar. Studies reported the odds ratio and 95% confidence interval (CI) (or provided sufficient information for calculation) of the association between hypertension and tinnitus were included. A total of 19 eligible studies with 20 effect estimates were used in this study. They included 63,154 participants with age ranging from 14 to 92. The pooled OR, which was pooled using a random effects model, was 1.37 (95% CI: 1.16 to 1.62). There was no evidence of publication bias (p = 0.11 for Begg's test, p = 0.96 for Egger's test). By meta-regression, we found that study design may be one possible factor of heterogeneity. Sensitivity analysis found that the result was stable. This study suggests that hypertension might be one risk factor of tinnitus, and hypertension prevention and control might be helpful in preventing tinnitus. PMID:26881064

  2. Association of Oxytocin Receptor Gene (OXTR) rs53576 Polymorphism with Sociality: A Meta-Analysis

    PubMed Central

    Li, Jingguang; Zhao, Yajun; Li, Rena; Broster, Lucas S.; Zhou, Chenglin; Yang, Suyong

    2015-01-01

    A common variant in the oxytocin receptor gene (OXTR), rs53576, has been broadly linked to socially related personality traits and behaviors. However, the pattern of published results is inconsistent. Here, we performed a meta-analysis to comprehensively evaluate the association. The literature was searched for relevant studies and effect sizes between individuals homozygous for the G allele (GG) and individuals with A allele carriers (AA/AG). Specifically, two indices of sociality were evaluated independently: i) general sociality (24 samples, n = 4955), i.e., how an individual responds to other people in general; and ii) close relationships (15 samples, n = 5262), i.e., how an individual responds to individuals with closed connections (parent-child or romantic relationship). We found positive association between the rs53576 polymorphism and general sociality (Cohen’s d = 0.11, p = .02); G allele homozygotes had higher general sociality than the A allele carriers. However, the meta-analyses did not detect significant genetic association between rs53576 and close relationships (Cohen’s d = 0.01, p = .64). In conclusion, genetic variation in the rs53576 influences general sociality, which further implies that it is worthy to systematically examine whether the rs53576 is a valid genetic marker for socially related psychiatric disorders. PMID:26121678

  3. Systematic review and meta-analysis of the association between frailty and outcome in surgical patients.

    PubMed

    Oakland, K; Nadler, R; Cresswell, L; Jackson, D; Coughlin, P A

    2016-02-01

    Introduction Frailty is becoming increasingly prevalent in the elderly population although a lack of consensus regarding a clinical definition hampers comparison of clinical studies. More elderly patients are being assessed for surgical intervention but the effect of frailty on surgical related outcomes is still not clear. Methods A systematic literature search for studies prospectively reporting frailty and postoperative outcomes in patients undergoing surgical intervention was performed with data collated from a total of 12 studies. Random effects meta-analysis modelling was undertaken to estimate the association between frailty and mortality rates (in-hospital and one-year), length of hospital stay and the need for step-down care for further rehabilitation/nursing home placement. Results Frailty was associated with a higher in-hospital mortality rate (pooled odds ratio [OR]: 2.77, 95% confidence interval [CI]: 1.62-4.73), a higher one-year mortality rate (pooled OR: 1.99, 95% CI: 1.49-2.66), a longer hospital stay (pooled mean difference: 1.05 days, 95% CI: 0.02-2.07 days) and a higher discharge rate to further rehabilitation/step-down care (pooled OR: 5.71, 95% CI: 3.41-9.55). Conclusions The presence of frailty in patients undergoing surgical intervention is associated with poorer outcomes with regard to mortality and return to independence. Further in-depth studies are required to identify factors that can be optimised to reduce the burden of frailty in surgical patients. PMID:26741674

  4. Association between Metformin Therapy and Breast Cancer Incidence and Mortality: Evidence from a Meta-Analysis

    PubMed Central

    Yang, Ting; Yang, Yuan

    2015-01-01

    Purpose Metformin may be associated with a decreased risk of breast cancer. We performed a meta-analysis to assess the effect of metformin intake on breast cancer risk and mortality. Methods We performed a PubMed and EMbase search for all available studies that described the risk of breast cancer and all-cause mortality in relation to the use of metformin among patients with type 2 diabetes mellitus. Pooled relative risks (RRs) were determined using a random effects model to assess the strength of association between metformin and the risk of breast cancer. Results Fifteen articles from PubMed satisfied the inclusion criteria, including a total of 838,333 participants. Compared with the control group, metformin use was not related to a reduced incidence of breast cancer (RR, 0.964; 95% confidence interval [CI], 0.761-1.221; p=0.761). However, metformin therapy was associated with decreased all-cause mortality (RR, 0.652; 95% CI, 0.488-0.873; p=0.004). No obvious publication bias was detected (incidence: pBegg=0.755, pEgger=0.008; mortality: pBegg=0.072, pEgger=0.185). Conclusion The present study suggested that metformin therapy may decrease the all-cause mortality of patients affected by breast cancer. However, this finding should be considered carefully and confirmed with further studies. PMID:26472977

  5. Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility.

    PubMed

    Yin, Xianyong; Low, Hui Qi; Wang, Ling; Li, Yonghong; Ellinghaus, Eva; Han, Jiali; Estivill, Xavier; Sun, Liangdan; Zuo, Xianbo; Shen, Changbing; Zhu, Caihong; Zhang, Anping; Sanchez, Fabio; Padyukov, Leonid; Catanese, Joseph J; Krueger, Gerald G; Duffin, Kristina Callis; Mucha, Sören; Weichenthal, Michael; Weidinger, Stephan; Lieb, Wolfgang; Foo, Jia Nee; Li, Yi; Sim, Karseng; Liany, Herty; Irwan, Ishak; Teo, Yikying; Theng, Colin T S; Gupta, Rashmi; Bowcock, Anne; De Jager, Philip L; Qureshi, Abrar A; de Bakker, Paul I W; Seielstad, Mark; Liao, Wilson; Ståhle, Mona; Franke, Andre; Zhang, Xuejun; Liu, Jianjun

    2015-01-01

    Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations. PMID:25903422

  6. Association between GRK4 and DRD1 gene polymorphisms and hypertension: a meta-analysis

    PubMed Central

    Zhang, He; Sun, Zhao-qing; Liu, Shuang-shuang; Yang, Li-na

    2016-01-01

    The role of GRK4 and DRD1 genes in hypertension remains controversial. We performed a meta-analysis to determine whether GRK4 and DRD1 polymorphisms influence the risk of hypertension and examined the relationship between the genetic variances and the etiology of hypertension. Relevant case-control studies were retrieved by database searches and selected according to established inclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. Meta-regression, subgroup analysis, and sensitivity analysis were performed. A total of 15 articles containing 29 studies were finally included. In the dominant model, rs4532 locus of DRD1 gene was related to hypertension with a pooled OR of 1.353 (95% CI =1.016–1.802, P=0.038). Subgroup analysis for ethnicity showed that rs1024323 locus of GRK4 gene was associated with hypertension in Caucasians (OR =1.826, 95% CI =1.215–2.745, P=0.004) but not in East Asians and Africans. Rs4532 locus was associated with hypertension in East Asians (OR =1.833, 95% CI =1.415–2.376, P,0.001) but not in Caucasians. These data provide possible references for future case-control studies in hypertension. PMID:26730182

  7. Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility

    PubMed Central

    Yin, Xianyong; Low, Hui Qi; Wang, Ling; Li, Yonghong; Ellinghaus, Eva; Han, Jiali; Estivill, Xavier; Sun, Liangdan; Zuo, Xianbo; Shen, Changbing; Zhu, Caihong; Zhang, Anping; Sanchez, Fabio; Padyukov, Leonid; Catanese, Joseph J.; Krueger, Gerald G.; Duffin, Kristina Callis; Mucha, Sören; Weichenthal, Michael; Weidinger, Stephan; Lieb, Wolfgang; Foo, Jia Nee; Li, Yi; Sim, Karseng; Liany, Herty; Irwan, Ishak; Teo, Yikying; Theng, Colin T. S.; Gupta, Rashmi; Bowcock, Anne; De Jager, Philip L.; Qureshi, Abrar A.; de Bakker, Paul I. W.; Seielstad, Mark; Liao, Wilson; Ståhle, Mona; Franke, Andre; Zhang, Xuejun; Liu, Jianjun

    2015-01-01

    Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations. PMID:25903422

  8. Genetic Variants Associated with Breast Cancer Risk: Comprehensive Field Synopsis, Meta-Analysis, and Epidemiologic Evidence

    PubMed Central

    Zhang, Ben; Beeghly-Fadiel, Alicia; Long, Jirong; Zheng, Wei

    2011-01-01

    SUMMARY Background Over 1,000 reports have been published during the past two decades on associations between genetic variants in candidate genes and breast cancer risk. Results have been generally inconsistent. We conducted literature searches and meta-analyses to provide a field synopsis of the current understanding of the genetic architecture of breast cancer risk. Methods Systematic literature searches for candidate gene association studies of breast cancer risk were conducted in two stages using PubMed on or before February 28, 2010. A total of 24,500 publications were identified, of which, 1,059 were deemed eligible for inclusion. Meta-analyses were conducted for 279 genetic variants in 128 candidate genes or chromosomal loci that had a minimum of three data sources available. Variants with significant associations by meta-analysis were assessed using the Venice criteria and scored as having strong, moderate, or weak cumulative evidence for an association with breast cancer risk. Findings Fifty-one variants in 40 genes showed statistically significant associations with breast cancer risk. Cumulative epidemiologic evidence for an association with breast cancer risk was graded as strong for 10 variants in six genes (ATM, CASP8, CHEK2, CTLA4, NBN, and TP53), moderate for four variants in four genes (ATM, CYP19A1, TERT, and XRCC3), and weak for 37 additional variants. Additionally, in meta-analyses that included a minimum of 10,000 cases and 10,000 controls, convincing evidence of no association with breast cancer risk was identified for 45 variants in 37 genes. Interpretation While most genetic variants evaluated in previous candidate gene studies showed no association with breast cancer risk in meta-analyses, 14 variants in 9 genes were found to have moderate to strong evidence for an association with breast cancer risk. Further evaluation of these variants is warranted. PMID:21514219

  9. Association Between Interleukin-6 Gene Polymorphisms and Bone Mineral Density: A Meta-Analysis

    PubMed Central

    Wang, Zhao; Yang, Yonghong; He, Minjuan; Wang, Ran; Ma, Juming; Zhang, Yimin; Zhao, Lingyun

    2013-01-01

    Background: Many studies have examined the association between interleukin-6 (IL-6) gene polymorphisms and bone mineral density (BMD). However, the results remain conflicting. To assess the relationship more precisely, a meta-analysis was performed. Methods: The PubMed, Embase, Chinese BioMedical Literature (CBM), Wanfang, and China National Knowledge Infrastructure (CNKI) database were searched for relevant articles published up to March 2013. Weighted mean difference (WMD) and 95% confidence interval (95% CI) were calculated using a fixed-effects or random-effects model. Results: A total of 16 articles with 11,957 subjects were investigated in this meta-analysis. Overall, −634C/G polymorphism was significantly associated with BMD at the femoral neck (WMD, −0.016 g/cm2; 95% CI, −0.028 to −0.003 g/cm2), lumbar spine (WMD, −0.049 g/cm2; 95% CI, −0.069 to −0.030 g/cm2), and whole body (WMD, −0.023 g/cm2; 95% CI, −0.037 to −0.009 g/cm2) for GG versus CC+CG. In subgroup analyses stratified by ethnicity, individuals carrying −634GG genotype had a significantly lower mean BMD at any skeletal site examined, compared with individuals with −634CC or −634CG genotype in Asian populations. For −174G/C polymorphism, the BMD differences between CC+CG and GG genotype were 0.004 g/cm2 at the distal radius (95% CI, 0.004 to 0.005 g/cm2), 0.011 g/cm2 at the trochanter (95% CI, 0.002 to 0.020 g/cm2), and 0.017 g/cm2 at the Ward's triangle (95% CI, 0.003 to 0.032 g/cm2). No significant publication bias was observed in either the −634C/G or −174G/C polymorphism. Conclusions: This suggests that there are modest effects of the −634C/G and −174G/C polymorphisms on BMD. Large-scale and well-designed studies are required to further investigate gene–gene and gene–environment interactions on IL-6 polymorphisms and BMD in various populations. PMID:24053561

  10. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

    PubMed Central

    Berndt, Sonja I.; Camp, Nicola J.; Skibola, Christine F.; Vijai, Joseph; Wang, Zhaoming; Gu, Jian; Nieters, Alexandra; Kelly, Rachel S.; Smedby, Karin E.; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia S.; Lan, Qing; Teras, Lauren R.; Machado, Moara; Yeager, Meredith; Brooks-Wilson, Angela R.; Hartge, Patricia; Purdue, Mark P.; Birmann, Brenda M.; Vajdic, Claire M.; Cocco, Pierluigi; Zhang, Yawei; Giles, Graham G.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Burdett, Laurie; Hutchinson, Amy; Ye, Yuanqing; Call, Timothy G.; Shanafelt, Tait D.; Novak, Anne J.; Kay, Neil E.; Liebow, Mark; Cunningham, Julie M.; Allmer, Cristine; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T.; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A.; Diver, W Ryan; Link, Brian K.; Weiner, George J.; Conde, Lucia; Bracci, Paige M.; Riby, Jacques; Arnett, Donna K.; Zhi, Degui; Leach, Justin M.; Holly, Elizabeth A.; Jackson, Rebecca D.; Tinker, Lesley F.; Benavente, Yolanda; Sala, Núria; Casabonne, Delphine; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Chaffee, Kari G.; Achenbach, Sara J.; Vachon, Celine M.; Goldin, Lynn R.; Strom, Sara S.; Leis, Jose F.; Weinberg, J. Brice; Caporaso, Neil E.; Norman, Aaron D.; De Roos, Anneclaire J.; Morton, Lindsay M.; Severson, Richard K.; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María- Dolores; Vermeulen, Roel C. H.; Travis, Ruth C.; Southey, Melissa C.; Milne, Roger L.; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R.; Villano, Danylo J.; Maria, Ann; Spinelli, John J.; Gascoyne, Randy D.; Connors, Joseph M.; Bertrand, Kimberly A.; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Ennas, Maria Grazia; Ferri, Giovanni M.; Miligi, Lucia; Liang, Liming; Ma, Baoshan; Huang, Jinyan; Crouch, Simon; Park, Ju-Hyun; Chatterjee, Nilanjan; North, Kari E.; Snowden, John A.; Wright, Josh; Fraumeni, Joseph F.; Offit, Kenneth; Wu, Xifeng; de Sanjose, Silvia; Cerhan, James R.; Chanock, Stephen J.; Rothman, Nathaniel; Slager, Susan L.

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P<5 × 10−7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10−8) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10−7). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility. PMID:26956414

  11. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.

    PubMed

    Berndt, Sonja I; Camp, Nicola J; Skibola, Christine F; Vijai, Joseph; Wang, Zhaoming; Gu, Jian; Nieters, Alexandra; Kelly, Rachel S; Smedby, Karin E; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia S; Lan, Qing; Teras, Lauren R; Machado, Moara; Yeager, Meredith; Brooks-Wilson, Angela R; Hartge, Patricia; Purdue, Mark P; Birmann, Brenda M; Vajdic, Claire M; Cocco, Pierluigi; Zhang, Yawei; Giles, Graham G; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Burdett, Laurie; Hutchinson, Amy; Ye, Yuanqing; Call, Timothy G; Shanafelt, Tait D; Novak, Anne J; Kay, Neil E; Liebow, Mark; Cunningham, Julie M; Allmer, Cristine; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A; Diver, W Ryan; Link, Brian K; Weiner, George J; Conde, Lucia; Bracci, Paige M; Riby, Jacques; Arnett, Donna K; Zhi, Degui; Leach, Justin M; Holly, Elizabeth A; Jackson, Rebecca D; Tinker, Lesley F; Benavente, Yolanda; Sala, Núria; Casabonne, Delphine; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Chaffee, Kari G; Achenbach, Sara J; Vachon, Celine M; Goldin, Lynn R; Strom, Sara S; Leis, Jose F; Weinberg, J Brice; Caporaso, Neil E; Norman, Aaron D; De Roos, Anneclaire J; Morton, Lindsay M; Severson, Richard K; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María-Dolores; Vermeulen, Roel C H; Travis, Ruth C; Southey, Melissa C; Milne, Roger L; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R; Villano, Danylo J; Maria, Ann; Spinelli, John J; Gascoyne, Randy D; Connors, Joseph M; Bertrand, Kimberly A; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Ennas, Maria Grazia; Ferri, Giovanni M; Miligi, Lucia; Liang, Liming; Ma, Baoshan; Huang, Jinyan; Crouch, Simon; Park, Ju-Hyun; Chatterjee, Nilanjan; North, Kari E; Snowden, John A; Wright, Josh; Fraumeni, Joseph F; Offit, Kenneth; Wu, Xifeng; de Sanjose, Silvia; Cerhan, James R; Chanock, Stephen J; Rothman, Nathaniel; Slager, Susan L

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility. PMID:26956414

  12. Association between Tooth Loss and Gastric Cancer: A Meta-Analysis of Observational Studies

    PubMed Central

    Luo, Hong; Zhao, Ke; Huang, Guang-Lei; Luo, Si-Yang; Peng, Ju-Xiang; Song, Ju-Kun

    2016-01-01

    Observational studies showed that tooth loss is associated with gastric cancer, but the findings are inconsistent. In this study, a meta-analysis was conducted to evaluate the relationship between tooth loss and gastric cancer. Relevant studies were screened in PubMed and Embase databases, and nine observational studies were considered eligible for the analysis. The combined relative risks for the highest versus the lowest categories of tooth loss were 1.86 (95% CI: 1.08–3.21) and 1.31 (95% CI: 1.12–1.53) in case control and cohort studies, respectively. However, unstable results were observed in the stratified and sensitivity analysis. The current evidence, based solely on four case-control studies and five cohort studies, suggested that tooth loss is a potential marker of gastric cancer. However, we can not concluded at this time that tooth loss may be a risk factor for gastric cancer due to significant heterogeneity among studies and mixed results between case-control studies and cohort studies. Additional large-scale and high-quality prospective studies are required to evaluate the association between tooth loss and risk of gastric cancer. PMID:26934048

  13. Impairments in facial affect recognition associated with autism spectrum disorders: a meta-analysis.

    PubMed

    Lozier, Leah M; Vanmeter, John W; Marsh, Abigail A

    2014-11-01

    Autism spectrum disorders (ASDs) are characterized by social impairments, including inappropriate responses to affective stimuli and nonverbal cues, which may extend to poor face-emotion recognition. However, the results of empirical studies of face-emotion recognition in individuals with ASD have yielded inconsistent findings that occlude understanding the role of face-emotion recognition deficits in the development of ASD. The goal of this meta-analysis was to address three as-yet unanswered questions. Are ASDs associated with consistent face-emotion recognition deficits? Do deficits generalize across multiple emotional expressions or are they limited to specific emotions? Do age or cognitive intelligence affect the magnitude of identified deficits? The results indicate that ASDs are associated with face-emotion recognition deficits across multiple expressions and that the magnitude of these deficits increases with age and cannot be accounted for by intelligence. These findings suggest that, whereas neurodevelopmental processes and social experience produce improvements in general face-emotion recognition abilities over time during typical development, children with ASD may experience disruptions in these processes, which suggested distributed functional impairment in the neural architecture that subserves face-emotion processing, an effect with downstream developmental consequences. PMID:24915526

  14. Meta-analysis of association between Helicobacter pylori infection and multiple sclerosis.

    PubMed

    Yao, Gang; Wang, Ping; Luo, Xiang-Dan; Yu, Ting-Min; Harris, Robert A; Zhang, Xing-Mei

    2016-05-01

    Despite recent research focus on the association between Helicobacter pylori (H. pylori) infection and multiple sclerosis (MS) there is no consensus about the findings. To obtain a more comprehensive estimate of the association we conducted a meta-analysis to determine the prevalence of H. pylori infection in MS patients and healthy controls. Pubmed and EMBASE were searched to identify eligible studies. Nine studies were selected for inclusion, involving 2806 cases (1553 patients with MS and 1253 controls). Overall, the prevalence of H. pylori infection in MS patients was lower than that in control groups (24.66% vs. 31.84%, OR=0.69, 95% CI: 0.57-0.83, P<0.0001). Subgroup analysis revealed that the levels of H.pylori infection among MS patients were lower than for control subjects in Western countries (11.90% vs. 16.08%, OR=0.63, 95% CI: 0.43-0.91, P=0.01), but were not statistically significant in Eastern countries (39.39% vs. 43.82%, OR=0.79, 95% CI: 0.55-1.14, P=0.20). Our data show that H. pylori infection and MS is negatively correlated, especially in Western countries. Whether H. pylori infection is a protective factor against MS risk should thus be addressed in large-scale and prospective studies. PMID:27033666

  15. Association between genetic polymorphisms in cytokine genes and recurrent miscarriage--a meta-analysis.

    PubMed

    Medica, Igor; Ostojic, Sasa; Pereza, Nina; Kastrin, Andrej; Peterlin, Borut

    2009-09-01

    A meta-analysis of association studies was performed to assess whether the reported genetic polymorphisms in cytokine genes are risk factors for recurrent miscarriage (RM). The electronic PubMed database was searched for case-control studies on immunity-related genes in RM. Investigations of a single polymorphism/gene involvement in RM reported more than five times were selected. Aggregating data from seven case-control studies on -308/tumour necrosis factor-alpha polymorphism, the odds ratio (OR) for RM was 1.1 (0.87-1.39) if the polymorphism was considered under a dominant genetic model. In six studies on -1082/interleukin-10 (IL-10) polymorphism, the OR under a dominant model was 0.76 (0.58-0.99), and under a recessive model the OR was 0.90 (0.71-1.15). In five case-control studies on -174/IL-6 polymorphism, the OR for RM under a recessive model was 1.29 (0.69-2.40). The results show a statistically significant association with RM for the -1082/IL-10 genotype. PMID:19778488

  16. Common variants in UMOD associate with urinary uromodulin levels: a meta-analysis.

    PubMed

    Olden, Matthias; Corre, Tanguy; Hayward, Caroline; Toniolo, Daniela; Ulivi, Sheila; Gasparini, Paolo; Pistis, Giorgio; Hwang, Shih-Jen; Bergmann, Sven; Campbell, Harry; Cocca, Massimiliano; Gandin, Ilaria; Girotto, Giorgia; Glaudemans, Bob; Hastie, Nicholas D; Loffing, Johannes; Polasek, Ozren; Rampoldi, Luca; Rudan, Igor; Sala, Cinzia; Traglia, Michela; Vollenweider, Peter; Vuckovic, Dragana; Youhanna, Sonia; Weber, Julien; Wright, Alan F; Kutalik, Zoltán; Bochud, Murielle; Fox, Caroline S; Devuyst, Olivier

    2014-08-01

    Uromodulin is expressed exclusively in the thick ascending limb and is the most abundant protein excreted in normal urine. Variants in UMOD, which encodes uromodulin, are associated with renal function, and urinary uromodulin levels may be a biomarker for kidney disease. However, the genetic factors regulating uromodulin excretion are unknown. We conducted a meta-analysis of urinary uromodulin levels to identify associated common genetic variants in the general population. We included 10,884 individuals of European descent from three genetic isolates and three urban cohorts. Each study measured uromodulin indexed to creatinine and conducted linear regression analysis of approximately 2.5 million single nucleotide polymorphisms using an additive model. We also tested whether variants in genes expressed in the thick ascending limb associate with uromodulin levels. rs12917707, located near UMOD and previously associated with renal function and CKD, had the strongest association with urinary uromodulin levels (P<0.001). In all cohorts, carriers of a G allele of this variant had higher uromodulin levels than noncarriers did (geometric means 10.24, 14.05, and 17.67 μg/g creatinine for zero, one, or two copies of the G allele). rs12446492 in the adjacent gene PDILT (protein disulfide isomerase-like, testis expressed) also reached genome-wide significance (P<0.001). Regarding genes expressed in the thick ascending limb, variants in KCNJ1, SORL1, and CAB39 associated with urinary uromodulin levels. These data indicate that common variants in the UMOD promoter region may influence urinary uromodulin levels. They also provide insights into uromodulin biology and the association of UMOD variants with renal function. PMID:24578125

  17. Common Variants in UMOD Associate with Urinary Uromodulin Levels: A Meta-Analysis

    PubMed Central

    Olden, Matthias; Corre, Tanguy; Hayward, Caroline; Toniolo, Daniela; Ulivi, Sheila; Gasparini, Paolo; Pistis, Giorgio; Hwang, Shih-Jen; Bergmann, Sven; Campbell, Harry; Cocca, Massimiliano; Gandin, Ilaria; Girotto, Giorgia; Glaudemans, Bob; Hastie, Nicholas D.; Loffing, Johannes; Polasek, Ozren; Rampoldi, Luca; Rudan, Igor; Sala, Cinzia; Traglia, Michela; Vollenweider, Peter; Vuckovic, Dragana; Youhanna, Sonia; Weber, Julien; Wright, Alan F.; Kutalik, Zoltán; Bochud, Murielle; Fox, Caroline S.

    2014-01-01

    Uromodulin is expressed exclusively in the thick ascending limb and is the most abundant protein excreted in normal urine. Variants in UMOD, which encodes uromodulin, are associated with renal function, and urinary uromodulin levels may be a biomarker for kidney disease. However, the genetic factors regulating uromodulin excretion are unknown. We conducted a meta-analysis of urinary uromodulin levels to identify associated common genetic variants in the general population. We included 10,884 individuals of European descent from three genetic isolates and three urban cohorts. Each study measured uromodulin indexed to creatinine and conducted linear regression analysis of approximately 2.5 million single nucleotide polymorphisms using an additive model. We also tested whether variants in genes expressed in the thick ascending limb associate with uromodulin levels. rs12917707, located near UMOD and previously associated with renal function and CKD, had the strongest association with urinary uromodulin levels (P<0.001). In all cohorts, carriers of a G allele of this variant had higher uromodulin levels than noncarriers did (geometric means 10.24, 14.05, and 17.67 μg/g creatinine for zero, one, or two copies of the G allele). rs12446492 in the adjacent gene PDILT (protein disulfide isomerase-like, testis expressed) also reached genome-wide significance (P<0.001). Regarding genes expressed in the thick ascending limb, variants in KCNJ1, SORL1, and CAB39 associated with urinary uromodulin levels. These data indicate that common variants in the UMOD promoter region may influence urinary uromodulin levels. They also provide insights into uromodulin biology and the association of UMOD variants with renal function. PMID:24578125

  18. Gene transcripts associated with muscle strength: a CHARGE meta-analysis of 7,781 persons.

    PubMed

    Pilling, L C; Joehanes, R; Kacprowski, T; Peters, M; Jansen, R; Karasik, D; Kiel, D P; Harries, L W; Teumer, A; Powell, J; Levy, D; Lin, H; Lunetta, K; Munson, P; Bandinelli, S; Henley, W; Hernandez, D; Singleton, A; Tanaka, T; van Grootheest, G; Hofman, A; Uitterlinden, A G; Biffar, R; Gläser, S; Homuth, G; Malsch, C; Völker, U; Penninx, B; van Meurs, J B J; Ferrucci, L; Kocher, T; Murabito, J; Melzer, D

    2016-01-01

    Lower muscle strength in midlife predicts disability and mortality in later life. Blood-borne factors, including growth differentiation factor 11 (GDF11), have been linked to muscle regeneration in animal models. We aimed to identify gene transcripts associated with muscle strength in adults. Meta-analysis of whole blood gene expression (overall 17,534 unique genes measured by microarray) and hand-grip strength in four independent cohorts (n = 7,781, ages: 20-104 yr, weighted mean = 56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, men/women). Expression levels of 221 genes were associated with strength after adjustment for cofactors and for multiple statistical testing, including ALAS2 (rate-limiting enzyme in heme synthesis), PRF1 (perforin, a cytotoxic protein associated with inflammation), IGF1R, and IGF2BP2 (both insulin like growth factor related). We identified statistical enrichment for hemoglobin biosynthesis, innate immune activation, and the stress response. Ten genes were associated only in younger individuals, four in men only and one in women only. For example, PIK3R2 (a negative regulator of PI3K/AKT growth pathway) was negatively associated with muscle strength in younger (<60 yr) individuals but not older (≥ 60 yr). We also show that 115 genes (52%) have not previously been linked to muscle in NCBI PubMed abstracts. This first large-scale transcriptome study of muscle strength in human adults confirmed associations with known pathways and provides new evidence for over half of the genes identified. There may be age- and sex-specific gene expression signatures in blood for muscle strength. PMID:26487704

  19. Gene transcripts associated with muscle strength: a CHARGE meta-analysis of 7,781 persons

    PubMed Central

    Joehanes, R.; Kacprowski, T.; Peters, M.; Jansen, R.; Karasik, D.; Kiel, D. P.; Harries, L. W.; Teumer, A.; Powell, J.; Levy, D.; Lin, H.; Lunetta, K.; Munson, P.; Bandinelli, S.; Henley, W.; Hernandez, D.; Singleton, A.; Tanaka, T.; van Grootheest, G.; Hofman, A.; Uitterlinden, A. G.; Biffar, R.; Gläser, S.; Homuth, G.; Malsch, C.; Völker, U.; Penninx, B.; van Meurs, J. B. J.; Ferrucci, L.; Kocher, T.; Murabito, J.

    2015-01-01

    Lower muscle strength in midlife predicts disability and mortality in later life. Blood-borne factors, including growth differentiation factor 11 (GDF11), have been linked to muscle regeneration in animal models. We aimed to identify gene transcripts associated with muscle strength in adults. Meta-analysis of whole blood gene expression (overall 17,534 unique genes measured by microarray) and hand-grip strength in four independent cohorts (n = 7,781, ages: 20–104 yr, weighted mean = 56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, men/women). Expression levels of 221 genes were associated with strength after adjustment for cofactors and for multiple statistical testing, including ALAS2 (rate-limiting enzyme in heme synthesis), PRF1 (perforin, a cytotoxic protein associated with inflammation), IGF1R, and IGF2BP2 (both insulin like growth factor related). We identified statistical enrichment for hemoglobin biosynthesis, innate immune activation, and the stress response. Ten genes were associated only in younger individuals, four in men only and one in women only. For example, PIK3R2 (a negative regulator of PI3K/AKT growth pathway) was negatively associated with muscle strength in younger (<60 yr) individuals but not older (≥60 yr). We also show that 115 genes (52%) have not previously been linked to muscle in NCBI PubMed abstracts. This first large-scale transcriptome study of muscle strength in human adults confirmed associations with known pathways and provides new evidence for over half of the genes identified. There may be age- and sex-specific gene expression signatures in blood for muscle strength. PMID:26487704

  20. Genetic associations in polypoidal choroidal vasculopathy: A systematic review and meta-analysis

    PubMed Central

    Liu, Ke; Chen, Li Jia; Hou, Ping; Chen, Weiqi; Pang, Chi Pui

    2012-01-01

    Purpose To investigate the genetic associations of polypoidal choroidal vasculopathy (PCV), the genetic difference between PCV and age-related macular degeneration (AMD), and the genotype-phenotype correlation of PCV. Methods A systematic review and meta-analysis were performed. Published articles about genetic associations of PCV identified from a literature search were reviewed. The following data from individual studies were extracted and analyzed: 1) comparison of genetic polymorphisms between PCV and controls; 2) comparison of genetic polymorphisms between PCV and AMD; and 3) comparison of phenotypes between different genotype groups. Results A total of 33 articles fulfilled the inclusion criteria. With meta-analyses, variants in four genes were found to be significantly associated with PCV: LOC387715 rs10490924 (n=9, allelic odds ratio [OR]=2.27, p<0.00001), HTRA1 rs11200638 (n=4, OR=2.72, p<0.00001), CFH rs1061170 (n=4, OR=1.72, p<0.00001), CFH rs800292 (n=5, OR=2.10, p<0.00001), and C2 rs547154 (n=3, OR=0.56, p=0.01). LOC387715 rs10490924 was the only variant showing a significant difference between PCV and wet AMD (n=5, OR=0.66, p<0.00001). The risk genotypes of rs10490924 were associated with larger lesion size, greater chance of vitreous hemorrhage, and worse therapeutic response in PCV. Conclusions LOC387715 rs10490924 was associated with PCV and its clinical manifestations, and showed a discrepant distribution between PCV and AMD. Variants in HTRA1, CFH, and C2 were also associated with PCV. PMID:22509112

  1. Association of traumatic brain injury with subsequent neurological and psychiatric disease: a meta-analysis.

    PubMed

    Perry, David C; Sturm, Virginia E; Peterson, Matthew J; Pieper, Carl F; Bullock, Thomas; Boeve, Bradley F; Miller, Bruce L; Guskiewicz, Kevin M; Berger, Mitchel S; Kramer, Joel H; Welsh-Bohmer, Kathleen A

    2016-02-01

    OBJECT Mild traumatic brain injury (TBI) has been proposed as a risk factor for the development of Alzheimer's disease, Parkinson's disease, depression, and other illnesses. This study's objective was to determine the association of prior mild TBI with the subsequent diagnosis (that is, at least 1 year postinjury) of neurological or psychiatric disease. METHODS All studies from January 1995 to February 2012 reporting TBI as a risk factor for diagnoses of interest were identified by searching PubMed, study references, and review articles. Reviewers abstracted the data and assessed study designs and characteristics. RESULTS Fifty-seven studies met the inclusion criteria. A random effects meta-analysis revealed a significant association of prior TBI with subsequent neurological and psychiatric diagnoses. The pooled odds ratio (OR) for the development of any illness subsequent to prior TBI was 1.67 (95% CI 1.44-1.93, p < 0.0001). Prior TBI was independently associated with both neurological (OR 1.55, 95% CI 1.31-1.83, p < 0.0001) and psychiatric (OR 2.00, 95% CI 1.50-2.66, p < 0.0001) outcomes. Analyses of individual diagnoses revealed higher odds of Alzheimer's disease, Parkinson's disease, mild cognitive impairment, depression, mixed affective disorders, and bipolar disorder in individuals with previous TBI as compared to those without TBI. This association was present when examining only studies of mild TBI and when considering the influence of study design and characteristics. Analysis of a subset of studies demonstrated no evidence that multiple TBIs were associated with higher odds of disease than a single TBI. CONCLUSIONS History of TBI, including mild TBI, is associated with the development of neurological and psychiatric illness. This finding indicates that either TBI is a risk factor for heterogeneous pathological processes or that TBI may contribute to a common pathological mechanism. PMID:26315003

  2. Genetic variants associated with gestational diabetes mellitus: a meta-analysis and subgroup analysis

    PubMed Central

    Wu, Ling; Cui, Long; Tam, Wing Hung; Ma, Ronald C. W.; Wang, Chi Chiu

    2016-01-01

    Previous studies have demonstrated that gestational diabetes mellitus (GDM) and Type 2 diabetes mellitus (T2D) share common genetic polymorphisms. We conducted meta-analysis and subgroup analysis of all available variants and determined the effects of confounding and experimental components on the genetic association of GDM. Any case-controlled or cohort studies with genotype distribution compared GDM cases with controls were included. In total, 28 articles including 8,204 cases and 15,221 controls for 6 polymorphisms were studied. rs10830963(MTNR1B), rs7903146(TCF7L2), and rs1801278(IRS1) were significantly associated with the increased GDM risk. The association of rs4402960(IGF2BP2) and rs1800629(TNF-α) was significant only when the studies with control allele frequency deviation and publication bias were excluded. Further subgroup analysis showed the risk alleles of rs7903146(TCF7L2) and rs1801282(PPARG) were significantly associated with the GDM risk only in Asian, but not in Caucasian population. The OGTT test using 100 g, but not 75 g; and genotype detection by other assays, but not Taqman method, were also significantly associated with increased GDM risk in rs1801278(IRS1) and rs7903146(TCF7L2). Overall GDM was associated with rs10830963(MTNR1B), rs7903146(TCF7L2), and rs1801278(IRS1), but only rs7903146(TCF7L2) and rs1801282(PPARG) were significant in Asian populations. While rs1801278(IRS1) and rs7903146(TCF7L2) were significantly affected by OGTT protocol and genotyping methods. PMID:27468700

  3. The seasonality of slipped upper femoral epiphysis--meta-analysis: a possible association with vitamin D.

    PubMed

    Farrier, Adam J; Ihediwa, Ugwunna; Khan, Shoaib; Kumar, Ameet; Gulati, Vivek; Uzoigwe, Chika E; Choudhury, Muhammed Z

    2015-01-01

    We performed a meta-analysis of studies evaluating the seasonality of slipped upper femoral epiphysis (SUFE). In addition we compared the monthly incidences of SUFE at latitudes greater than 40° with the established serum 25-hydroxyvitamin levels for children resident at a comparative latitude. In total 11 relevant studies were identified, involving 7451 cases of SUFE. There was significant variation in the month of onset of SUFE. The degree of variability increased with increasing latitude. The modal month of symptomatic onset was dependent upon latitude. At latitudes greater than 40°, the most common month of onset was August. At latitudes between 20° and 40°, this was earlier in the calendar year, around April. The seasonal variability was statistically significant (p<0.0001 and p<0.005 for latitudes >40° and 20°-40° respectively). The pattern of monthly fluctuation in onset of SUFE very closely mirrored the monthly pattern of variation for serum 25-hydroxyvitamin D3. There was a very strong positive correlation (Spearman rank rho = + 0.8, p = 0.001). There is a monthly variation in incidence of SUFE. The degree of variability increases with increasing latitude. There may be an association with vitamin D. We hypothesise that elevated serum 25-hydroxyvitamin D3 accelerates growth thus rendering the growth plate vulnerable to slippage in analogous manner to the pubertal growth spurt. PMID:26044532

  4. Association between pesticide exposure and risk of kidney cancer: a meta-analysis

    PubMed Central

    Xie, Bo; Hu, Yingfang; Liang, Zhen; Liu, Ben; Zheng, Xiangyi; Xie, Liping

    2016-01-01

    This meta-analysis aimed to evaluate the correlation between pesticide exposure and kidney cancer. We conducted a systematic search of the Cochrane Library, Embase, Web of Knowledge, and Medline (updated to March 1, 2015) to identify all relevant studies. References of the retrieved articles were also identified. Fixed- or random-effect models were used to summarize the estimates of relative risk (RR) with 95% confidence interval for the association between exposure of pesticide and risk of kidney cancer. The pooled RR estimate indicated that pesticide exposure might have an elevated risk for kidney cancer (RR =1.10, 95% confidence interval 1.01–1.19). In a subgroup analysis of high quality articles, we detected that pesticide exposure is a significant risk factor for kidney cancer in a subgroup analysis of case-control studies, (Newcastle–Ottawa Quality Assessment Scale score >6) (RR =1.31, 95% confidence interval 1.12–1.51). North America studies, odds ratio studies, and studies with effect estimate adjusted for more than two confounder studies. In conclusion, pesticide exposure may be a risk factor for kidney cancer. PMID:27418833

  5. GRIK4 polymorphism and its association with antidepressant response in depressed patients: a meta-analysis

    PubMed Central

    Kawaguchi, Daniel M; Glatt, Stephen J

    2014-01-01

    Aim This study aimed to evaluate the relationship between a human GRIK4 gene polymorphism (rs1954787) and responsiveness to antidepressant treatment in depressed patients. Methods A meta-analysis was carried out on five studies. Pooled odds ratios (ORs), 95% CIs and a χ2 test measuring heterogeneity were calculated. A test of publication bias was also conducted. Results Alleles and genotypes from a total of 2169 depressed patients were analyzed. The results showed that the C allele appeared more frequently than the T allele in responders to treatment (OR: 1.22; 95% CI: 1.035–1.445; z = 2.36; p = 0.018). Similarly, CC homozygotes were more likely than TT homozygotes to respond to treatment (OR: 1.45; 95% CI: 1.107–1.913; z = 2.69; p = 0.007). No evidence of publication bias was detected. Conclusion Subjects possessing the C allele or CC genotype of the GRIK4 polymorphism rs1954787 are more likely to respond to antidepressant treatment relative to subjects harboring the T allele and TT genotype. Additional replication of this result is required before this association can be considered definitive, after which it may become possible to employ this marker in conjunction with other known predictors in order to anticipate the outcomes of treatment with antidepressant medications. PMID:25303296

  6. Association of homocysteine with type 1 diabetes mellitus: a meta-analysis

    PubMed Central

    Feng, Yu; Shan, Mei-Qin; Bo, Lin; Zhang, Xiao-Yan; Hu, Ji

    2015-01-01

    Purpose: To figure out the association between plasma Hcy status and type 1 diabetes mellitus (T1DM). Methods: We searched the PubMed Web of Science, and The Cochrane Library to identify eligible studies. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of selected studies. All analyses were performed using the STATA, version 12 software. Results: 15 studies were included in this investigation. Our meta-analysis indicated that plasma Hcy concentrations in T1DM patients without any complications were normal compared with healthy people [13 studies, SMD: -0.08, 95% confidence interval (CI): -0.44 to 0.28, P=0.67]. However, a significant elevation of plasma Hcy concentrations was observed in T1DM patients with only diabetic retinopathy (DR) (5 studies, SMD: 0.34, 95% CI: 0.13 to 0.55, P=0.002), only diabetic nephropathy (DN) (4 studies, SMD: 0.76, 95% CI: 0.18 to 1.33, P=0.01) and both the two complications (3 studies, SMD: 1.05, 95% CI: 0.03 to 2.07, P=0.043) compared with T1DM patients without any complications. Conclusions: Homocysteine levels elevate in T1DM patients with DR and DN, but don’t elevate in T1DM without any complications. PMID:26550163

  7. Association between Serum TNF-α Levels and Recurrent Spontaneous Miscarriage: A Meta-analysis.

    PubMed

    Zhang, Chengdong; Deng, Xiaozhen; Zhang, Xuerong; Pan, Zhengyan; Zhao, Wei; Zhang, Yuening; Li, Jiatong; Xiao, Feifan; Wu, Huayu; Tan, Hezhang; Guo, Peifen; Yang, Xiaoli

    2016-02-01

    Most recurrent spontaneous miscarriages (RSMs) are attributed to 'unexplained' factors, the majority of which are immune factors. Furthermore, clinically, only a small number of RSM patients get early diagnosis by testing for antiphospholipid antibodies, whereas most of the patients, present no specific diagnostic indicators. We performed a meta-analysis of observational studies to detect the association between RSM and TNF-α levels. We searched PubMed, EMBase, ScienceDirect, Web of Science, and Chinese databases (including: Wanfang Data, CNKI, and VIP databases) for articles published up to 2014. Of the 151 initially identified studies, 11 case-control studies with 1371 patients were finally analyzed. Overall, baseline TNF-α levels were higher in patients than in controls. The standardized mean difference of the TNF-α levels of the patients was 2.82 units (95% confidence interval 1.57-4.06) and the overall effect z-score was 4.42 (P < 0.0001). The heterogeneity test revealed significant differences among individual studies (P = 0.000, I(2)  = 98.7%). Serum TNF-α levels were significantly increased in patients relative to those in controls. The heterogeneity could be attributed to the differences in the detection methods and sampling times used in the different studies. PMID:26585408

  8. Exploring compassion: a meta-analysis of the association between self-compassion and psychopathology.

    PubMed

    MacBeth, Angus; Gumley, Andrew

    2012-08-01

    Compassion has emerged as an important construct in studies of mental health and psychological therapy. Although an increasing number of studies have explored relationships between compassion and different facets of psychopathology there has as yet been no systematic review or synthesis of the empirical literature. We conducted a systematic search of the literature on compassion and mental health. We identified 20 samples from 14 eligible studies. All studies used the Neff Self Compassion Scale (Neff, 2003b). We employed meta-analysis to explore associations between self-compassion and psychopathology using random effects analyses of Fisher's Z correcting for attenuation arising from scale reliability. We found a large effect size for the relationship between compassion and psychopathology of r=-0.54 (95% CI=-0.57 to -0.51; Z=-34.02; p<.0001). Heterogeneity was significant in the analysis. There was no evidence of significant publication bias. Compassion is an important explanatory variable in understanding mental health and resilience. Future work is needed to develop the evidence base for compassion in psychopathology, and explore correlates of compassion and psychopathology. PMID:22796446

  9. The nitric oxide synthase 3 G894T polymorphism associated with Alzheimer’s disease risk: a meta-analysis

    PubMed Central

    Liu, Shengyuan; Zeng, Fangfang; Wang, Changyi; Chen, Zhongwei; Zhao, Bin; Li, Keshen

    2015-01-01

    The association between the G894T polymorphism (Glu298Asp) of nitric oxide synthase 3 (NOS3) and risk of Alzheimer’s disease (AD) was explored by performing a meta-analysis of case-control studies. Bibliographical searches were conducted in the MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases without any language limitations. Two investigators independently assessed abstracts for relevant studies, and reviewed all eligible studies. We adopted regrouping in accordance with the most probably appropriate genetic model. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of this association. We performed a meta-analysis including 21 published articles with 23 case-control studies (5,670 cases and 5,046 controls). In the analyses, we found significant association between G894T polymorphism and AD risk under a complete overdominant model (GG + TT vs. GT) (OR = 1.18; 95%CI, 1.04–1.35; P = 0.010). When stratified by time of AD onset, we found the association between this polymorphism and AD susceptibility to be more substantial among late onset patients than among early onset patients (OR for late vs. early onset: 1.33 vs. 1.02, P interaction = 0.049). The meta-analysis showed that the polymorphism G894T of NOS3 was associated with risk of AD. PMID:26337484

  10. Biomechanical factors associated with the development of tibiofemoral knee osteoarthritis: protocol for a systematic review and meta-analysis

    PubMed Central

    van Tunen, Joyce A C; Dell'Isola, Andrea; Juhl, Carsten; Dekker, Joost; Steultjens, Martijn; Lund, Hans

    2016-01-01

    Introduction Altered biomechanics, increased joint loading and tissue damage, might be related in a vicious cycle within the development of knee osteoarthritis (KOA). We have defined biomechanical factors as joint-related factors that interact with the forces, moments and kinematics in and around a synovial joint. Although a number of studies and systematic reviews have been performed to assess the association of various factors with the development of KOA, a comprehensive overview focusing on biomechanical factors that are associated with the development of KOA is not available. The aim of this review is (1) to identify biomechanical factors that are associated with (the development of) KOA and (2) to identify the impact of other relevant risk factors on this association. Methods and analysis Cohort, cross-sectional and case–control studies investigating the association of a biomechanical factor with (the development of) KOA will be included. MEDLINE, EMBASE, CINAHL and SPORTDiscus will be searched from their inception until August 2015. 2 reviewers will independently screen articles obtained by the search for eligibility, extract data and score risk of bias. Quality of evidence will be evaluated. Meta-analysis using random effects model will be applied in each of the biomechanical factors, if possible. Ethics and dissemination This systematic review and meta-analysis does not require ethical approval. The results of this systematic review and meta-analysis will be disseminated through publications in peer-reviewed journals and presentations at (inter)national conferences. Trial registration number CRD42015025092. PMID:27311908

  11. Association between antiretroviral therapy adherence and employment status: systematic review and meta-analysis

    PubMed Central

    Uthman, Olalekan A; Peltzer, Karl; Richardson, Lindsey A; Mills, Edward J; Amekudzi, Kofi; Ouédraogo, Alice

    2015-01-01

    Abstract Objective To assess the association between the employment status of human immunodeficiency virus (HIV)-infected individuals and adherence to antiretroviral therapy (ART). Methods We searched the Medline, Embase and Cochrane Central Register of Controlled Trials databases for studies reporting ART adherence and employment status published between January 1980 and September 2014. Information from a wide range of other sources, including the grey literature, was also analysed. Two independent reviewers extracted data on treatment adherence and study characteristics. Study data on the association between being employed and adhering to ART were pooled using a random-effects model. Between-study heterogeneity and sources of bias were evaluated. Findings The meta-analysis included 28 studies published between 1996 and 2014 that together involved 8743 HIV-infected individuals from 14 countries. The overall pooled odds ratio (OR) for the association between being employed and adhering to ART was 1.27 (95% confidence interval, CI: 1.04–1.55). The association was significant for studies from low-income countries (OR: 1.85, 95% CI: 1.58–2.18) and high-income countries (OR: 1.33, 95% CI: 1.02–1.74) but not middle-income countries (OR: 0.94, 95% CI: 0.62–1.42). In addition, studies published after 2011 and larger studies showed less association between employment and adherence than earlier and small studies, respectively. Conclusion Employed HIV-infected individuals, particularly those in low- and high-income countries, were more likely to adhere to ART than unemployed individuals. Further research is needed on the mechanisms by which employment and ART adherence affect each other and on whether employment-creation interventions can positively influence ART adherence, HIV disease progression and quality of life. PMID:25558105

  12. Association of Neonatal Hyperbilirubinemia with UGT1A1 Gene Polymorphisms: A Meta-Analysis

    PubMed Central

    Yu, Zibi; Zhu, Kaichang; Wang, Li; Liu, Ying; Sun, Jianmei

    2015-01-01

    Background The results of studies on association between the polymorphisms in the coding region and the promoter of uridine diphosphateglucuronosyl transferase 1A1 (UGT1A1) and neonatal hyperbilirubinemia are controversial. This study aimed to determine whether the UGT1A1 gene polymorphisms of Gly71Arg and TATA promoter were significant risk factors associated with neonatal hyperbilirubinemia. Material/Methods The PubMed, Cochrane Library, and Embase databases were searched for papers that describe the association between UGT1A1 polymorphisms and neonatal hyperbilirubinemia. Summary odds ratios and 95% confidence intervals (CI) were estimated based on a fixed-effects model or random-effects model, depending on the absence or presence of significant heterogeneity. Results A total of 32 eligible studies and 6520 participants were identified. Among them, 24 studies focused on the association of neonatal hyperbilirubinemia with UGT1A1 Gly71Arg polymorphisms, and a significant difference was found for the comparison of AA vs. AG+GG (OR=3.47, 95% CI=2.29–5.28, P<0.0001). We included 19 studies on the association of neonatal hyperbilirubinemia with UGT1A1 TATA promoter polymorphism, which also found a statistically significant difference between 7/7 and 6/7 + 6/6 (OR=2.24, 95% CI=1.29–3.92, P=0.004). Conclusions This meta-analysis demonstrated that UGT1A1 polymorphisms (Gly71Arg and TATA promoter) significantly increase the risk of neonatal hyperbilirubinemia. PMID:26467199

  13. No Association of SERPINE1 -675 Polymorphism With Sepsis Susceptibility: A Meta-Analysis.

    PubMed

    Shi, Chengfang; Sui, Zhifu; Li, Li; Yang, Rongya

    2015-11-01

    The serine protease inhibitor clade E member 1 (SERPINE1) gene has been suggested to exert great influence on the development of sepsis. But there is little overlap in the results of association between SERPINE1 -675 4G/5G polymorphism and sepsis.To get a more precise estimation of this association, we conducted a meta-analysis with a relatively larger sample size including 1806 cases and 2239 controls. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the relationship between -675 4G/5G polymorphism and sepsis susceptibility. Subgroup analyses were conducted based on ethnicity and source of controls.The results showed that there was no association of the SERPINE1 polymorphism and sepsis susceptibility (5G5G vs 4G4G: OR = 0.87, CI = 0.75-1.03; 5G5G+4G5G vs 4G4G: OR = 0.93, CI = 0.84-1.02; 5G5G vs 4G4G+4G5G: OR = 0.96, CI = 0.83-1.11; 5G vs 4G: OR = 0.94, CI = 0.86-1.01; 4G5G vs 4G4G: OR = 0.90, CI = 0.80-1.01). Nor did any subgroup analysis indicate a significant association.In conclusion, -675 4G/5G polymorphism in the SERPINE1 gene may not be associated with the risk of sepsis. PMID:26559247

  14. Association between angiotensinogen T174M polymorphism and ischemic stroke: A meta-analysis

    PubMed Central

    Ou, Zilin; Chen, Hongbing; Liu, Gang; Li, Chuo; Lin, Shaoying; Lin, Jianwen

    2015-01-01

    Background: Numerous studies have evaluated the association between the angiotensinogen (AGT) T174M polymorphism and ischemic stroke(IS) risk. However, the specific association is still controversial. Materials and Methods: In order to explore this association more deeply, we performed a meta-analysis. All of the relevant studies were identified from PubMed, Embase, and Chinese National Knowledge Infrastructure database up to October 2014. Statistical analyses were conducted with STATA 12.0 software. Odds ratio (OR) with 95% confidence interval (CI) values were applied to evaluate the strength of the association. Results: Six studies with 1290 cases and 1125 controls were included. No significant variation in IS risk was detected in any of the genetic models in the overall (MM vs. TT: OR = 1.64, 95% CI = 0.51-5.28; MT vs. TT: OR = 0.93, 95% CI = 0.66-1.31; dominant model: OR = 1.08, 95% CI = 0.69-1.72; recessive model: OR = 0.61,95% CI = 0.20-1.91). Taking into account the effect of ethnicity, further stratified analyses were performed. The results showed that AGT gene T174M polymorphism might be associated with IS risk in Asians (MM vs. TT: OR = 3.28, 95% CI = 1.79-6.02; recessive model: OR = 0.31, 95% CI = 0.17-0.57). Conclusion: In conclusion, the AGT T174M polymorphism may be a susceptible predictor of the risk of IS in Asians. Further, large and well-designed studies are needed to confirm this conclusion. PMID:26600839

  15. Association of homocysteine with type 2 diabetes: a meta-analysis implementing Mendelian randomization approach

    PubMed Central

    2013-01-01

    Background We tested the hypothesis that elevated homocysteine (Hcy) level is causally associated with increased risk of type 2 diabetes mellitus (T2DM). Results The meta-analysis and Mendelian randomization analysis were performed among 4011 cases and 4303 controls. The absolute pooled mean Hcy concentration in subjects with MTHFR 677TT was 5.55 μmol/L (95% CI, 1.33 to 9.77) greater than that in subjects with MTHFR 677CC in T2DM. Overall, the T allele of the MTHFR 677 C > T conferred a greater risk for T2DM [Random effect (RE) OR = 1.31(1.17-1.64), I2 = 41.0%, p = 0.055]. The random effect (RE) pooled OR associated with T2DM for MTHFR 677TT relative to the 677CC was [RE OR = 1.38(1.18-1.62)]. The fixed-effect pooled OR of the association for the MTHFR 677 TT vs CT was 1.29 (95% CI, 1.09-1.51). MTHFR 677 TT showed a significantly higher risk for T2DM compared with MTHFR 677 CC + CT [Fixed effect (FE) OR = 1.32(1.14-1.54), I2 = 0.0%, p = 0.686]. The absolute pooled mean Hcy concentration in individuals with T2DM was 0.94 μmol/L (95% CI, 0.40-1.48) greater than that in control subjects. The estimated causal OR associated with T2DM was 1.29 for 5 μmol/L increment in Hcy. Conclusions Our findings provided strong evidence on the causal association of Hcy level with the development of T2DM. PMID:24320691

  16. Meta-analysis of Gene-Level Associations for Rare Variants Based on Single-Variant Statistics

    PubMed Central

    Hu, Yi-Juan; Berndt, Sonja I.; Gustafsson, Stefan; Ganna, Andrea; Berndt, Sonja I.; Gustafsson, Stefan; Mägi, Reedik; Ganna, Andrea; Wheeler, Eleanor; Feitosa, Mary F.; Justice, Anne E.; Monda, Keri L.; Croteau-Chonka, Damien C.; Day, Felix R.; Esko, Tõnu; Fall, Tove; Ferreira, Teresa; Gentilini, Davide; Jackson, Anne U.; Luan, Jian’an; Randall, Joshua C.; Vedantam, Sailaja; Willer, Cristen J.; Winkler, Thomas W.; Wood, Andrew R.; Workalemahu, Tsegaselassie; Hu, Yi-Juan; Lee, Sang Hong; Liang, Liming; Lin, Dan-Yu; Min, Josine L.; Neale, Benjamin M.; Thorleifsson, Gudmar; Yang, Jian; Albrecht, Eva; Amin, Najaf; Bragg-Gresham, Jennifer L.; Cadby, Gemma; den Heijer, Martin; Eklund, Niina; Fischer, Krista; Goel, Anuj; Hottenga, Jouke-Jan; Huffman, Jennifer E.; Jarick, Ivonne; Johansson, Åsa; Johnson, Toby; Kanoni, Stavroula; Kleber, Marcus E.; König, Inke R.; Kristiansson, Kati; Kutalik, Zoltán; Lamina, Claudia; Lecoeur, Cecile; Li, Guo; Mangino, Massimo; McArdle, Wendy L.; Medina-Gomez, Carolina; Müller-Nurasyid, Martina; Ngwa, Julius S.; Nolte, Ilja M.; Paternoster, Lavinia; Pechlivanis, Sonali; Perola, Markus; Peters, Marjolein J.; Preuss, Michael; Rose, Lynda M.; Shi, Jianxin; Shungin, Dmitry; Smith, Albert Vernon; Strawbridge, Rona J.; Surakka, Ida; Teumer, Alexander; Trip, Mieke D.; Tyrer, Jonathan; Van Vliet-Ostaptchouk, Jana V.; Vandenput, Liesbeth; Waite, Lindsay L.; Zhao, Jing Hua; Absher, Devin; Asselbergs, Folkert W.; Atalay, Mustafa; Attwood, Antony P.; Balmforth, Anthony J.; Basart, Hanneke; Beilby, John; Bonnycastle, Lori L.; Brambilla, Paolo; Bruinenberg, Marcel; Campbell, Harry; Chasman, Daniel I.; Chines, Peter S.; Collins, Francis S.; Connell, John M.; Cookson, William; de Faire, Ulf; de Vegt, Femmie; Dei, Mariano; Dimitriou, Maria; Edkins, Sarah; Estrada, Karol; Evans, David M.; Farrall, Martin; Ferrario, Marco M.; Ferrières, Jean; Franke, Lude; Frau, Francesca; Gejman, Pablo V.; Grallert, Harald; Grönberg, Henrik; Gudnason, Vilmundur; Hall, Alistair S.; Hall, Per; Hartikainen, Anna-Liisa; Hayward, Caroline; Heard-Costa, Nancy L.; Heath, Andrew C.; Hebebrand, Johannes; Homuth, Georg; Hu, Frank B.; Hunt, Sarah E.; Hyppönen, Elina; Iribarren, Carlos; Jacobs, Kevin B.; Jansson, John-Olov; Jula, Antti; Kähönen, Mika; Kathiresan, Sekar; Kee, Frank; Khaw, Kay-Tee; Kivimaki, Mika; Koenig, Wolfgang; Kraja, Aldi T.; Kumari, Meena; Kuulasmaa, Kari; Kuusisto, Johanna; Laitinen, Jaana H.; Lakka, Timo A.; Langenberg, Claudia; Launer, Lenore J.; Lind, Lars; Lindström, Jaana; Liu, Jianjun; Liuzzi, Antonio; Lokki, Marja-Liisa; Lorentzon, Mattias; Madden, Pamela A.; Magnusson, Patrik K.; Manunta, Paolo; Marek, Diana; März, Winfried; Leach, Irene Mateo; McKnight, Barbara; Medland, Sarah E.; Mihailov, Evelin; Milani, Lili; Montgomery, Grant W.; Mooser, Vincent; Mühleisen, Thomas W.; Munroe, Patricia B.; Musk, Arthur W.; Narisu, Narisu; Navis, Gerjan; Nicholson, George; Nohr, Ellen A.; Ong, Ken K.; Oostra, Ben A.; Palmer, Colin N.A.; Palotie, Aarno; Peden, John F.; Pedersen, Nancy; Peters, Annette; Polasek, Ozren; Pouta, Anneli; Pramstaller, Peter P.; Prokopenko, Inga; Pütter, Carolin; Radhakrishnan, Aparna; Raitakari, Olli; Rendon, Augusto; Rivadeneira, Fernando; Rudan, Igor; Saaristo, Timo E.; Sambrook, Jennifer G.; Sanders, Alan R.; Sanna, Serena; Saramies, Jouko; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Shin, So-Youn; Signorini, Stefano; Sinisalo, Juha; Skrobek, Boris; Soranzo, Nicole; Stančáková, Alena; Stark, Klaus; Stephens, Jonathan C.; Stirrups, Kathleen; Stolk, Ronald P.; Stumvoll, Michael; Swift, Amy J.; Theodoraki, Eirini V.; Thorand, Barbara; Tregouet, David-Alexandre; Tremoli, Elena; Van der Klauw, Melanie M.; van Meurs, Joyce B.J.; Vermeulen, Sita H.; Viikari, Jorma; Virtamo, Jarmo; Vitart, Veronique; Waeber, Gérard; Wang, Zhaoming; Widén, Elisabeth; Wild, Sarah H.; Willemsen, Gonneke; Winkelmann, Bernhard R.; Witteman, Jacqueline C.M.; Wolffenbuttel, Bruce H.R.; Wong, Andrew; Wright, Alan F.

    2013-01-01

    Meta-analysis of genome-wide association studies (GWASs) has led to the discoveries of many common variants associated with complex human diseases. There is a growing recognition that identifying “causal” rare variants also requires large-scale meta-analysis. The fact that association tests with rare variants are performed at the gene level rather than at the variant level poses unprecedented challenges in the meta-analysis. First, different studies may adopt different gene-level tests, so the results are not compatible. Second, gene-level tests require multivariate statistics (i.e., components of the test statistic and their covariance matrix), which are difficult to obtain. To overcome these challenges, we propose to perform gene-level tests for rare variants by combining the results of single-variant analysis (i.e., p values of association tests and effect estimates) from participating studies. This simple strategy is possible because of an insight that multivariate statistics can be recovered from single-variant statistics, together with the correlation matrix of the single-variant test statistics, which can be estimated from one of the participating studies or from a publicly available database. We show both theoretically and numerically that the proposed meta-analysis approach provides accurate control of the type I error and is as powerful as joint analysis of individual participant data. This approach accommodates any disease phenotype and any study design and produces all commonly used gene-level tests. An application to the GWAS summary results of the Genetic Investigation of ANthropometric Traits (GIANT) consortium reveals rare and low-frequency variants associated with human height. The relevant software is freely available. PMID:23891470

  17. Meta-analysis of gene-level associations for rare variants based on single-variant statistics.

    PubMed

    Hu, Yi-Juan; Berndt, Sonja I; Gustafsson, Stefan; Ganna, Andrea; Hirschhorn, Joel; North, Kari E; Ingelsson, Erik; Lin, Dan-Yu

    2013-08-01

    Meta-analysis of genome-wide association studies (GWASs) has led to the discoveries of many common variants associated with complex human diseases. There is a growing recognition that identifying "causal" rare variants also requires large-scale meta-analysis. The fact that association tests with rare variants are performed at the gene level rather than at the variant level poses unprecedented challenges in the meta-analysis. First, different studies may adopt different gene-level tests, so the results are not compatible. Second, gene-level tests require multivariate statistics (i.e., components of the test statistic and their covariance matrix), which are difficult to obtain. To overcome these challenges, we propose to perform gene-level tests for rare variants by combining the results of single-variant analysis (i.e., p values of association tests and effect estimates) from participating studies. This simple strategy is possible because of an insight that multivariate statistics can be recovered from single-variant statistics, together with the correlation matrix of the single-variant test statistics, which can be estimated from one of the participating studies or from a publicly available database. We show both theoretically and numerically that the proposed meta-analysis approach provides accurate control of the type I error and is as powerful as joint analysis of individual participant data. This approach accommodates any disease phenotype and any study design and produces all commonly used gene-level tests. An application to the GWAS summary results of the Genetic Investigation of ANthropometric Traits (GIANT) consortium reveals rare and low-frequency variants associated with human height. The relevant software is freely available. PMID:23891470

  18. Association between G-217A polymorphism in the AGT gene and essential hypertension: a meta-analysis.

    PubMed

    Yao, R; Du, Y Y; Zhang, Y Z; Chen, Q H; Zhao, L S; Li, L

    2015-01-01

    Numerous studies have evaluated the association between the angiotensinogen (AGT) G-217A gene polymorphism and essential hypertension risk. However, the results have been inconsistent. We examined whether the AGT G-217A gene polymorphism confers essential hypertension risk by conducting a meta-analysis. We conducted a literature search of the Google Scholar, PubMed, and China National Knowledge Infrastructure databases for relevant studies that examined the G-217A polymorphism and risk of essential hypertension. Statistical analyses were carried out using Stata 12.0 to combine all relevant studies. Crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to estimate the strength of this association. A total of 2017 patients with psoriasis and 1708 controls from 7 comparative studies were included in this meta-analysis. We found a significant association between the AGT G-217A gene polymorphism and the risk of essential hypertension (AA vs GG: OR = 2.52, 95%CI = 1.68-3.78; AA vs GA: OR = 2.26, 95%CI = 1.48-3.45; dominant model: OR = 0.38, 95%CI = 0.26-0.57; recessive model: OR = 1.20, 95%CI = 1.03-1.39). Further stratified analyses were conducted by ethnicity and sample size and produced similar results. No evidence of publication bias was found. This meta-analysis confirms that the AGT G-217A gene polymorphism is associated with essential hypertension susceptibility. PMID:26125750

  19. A meta-analysis examining the independent association between thyroid nodule size and malignancy

    PubMed Central

    Hammad, AbdulRahman Y.; Noureldine, Salem I.; Hu, Tian; Ibrahim, Yasin; Masoodi, Hammad M.

    2016-01-01

    Background Tumor size is recognized as an important predictor of malignancy in many types of cancers. However, there is no clear line of characterization when it comes to the association between thyroid nodule size and malignancy risk prediction; and the current data remains inconsistent across different studies. The aim of our study is to examine the association between nodule size and malignancy using meta-analysis of the current literature. Methods Data sources were gathered through systemic search of PubMed, Embase and other scientific databases for articles published between January 1, 1996 and June 1, 2013. A reference group with nodule sizes <3 cm was set as a control group. Two other nodule size categories were established and these included nodules from 3–5.9 cm and nodules ≥6 cm in size. Primary outcome was a histologically proven malignancy per nodule size category. The effect sizes of clinicopathologic parameters, which are the quantitative measures of association strength between two variables, were calculated by the means of odds ratios (OR). The effect sizes were then combined using a random-effects model. Results Seven studies met our inclusion criteria with 10,817 thyroid nodules evaluated. Malignancy was identified in 2,206 (20.4%) nodules. After adjusting for patient age and gender, nodules that measured 3–5.9 cm had a 26% greater malignancy risk compared to those measuring <3 cm [OR, 1.26; 95% confidence interval (CI): 1.13–1.39]. However, nodules 6 cm or larger had a 16% lower risk of malignancy compared to those measuring <3 cm (OR, 0.84; 95% CI: 0.73–0.98). Conclusions Thyroid nodule size predicts cancer risk. However, a threshold effect of thyroid nodule size 6 cm or greater is significantly associated with a more benign disease. PMID:27294039

  20. Associations between nitric oxide synthase 3 gene polymorphisms and preeclampsia risk: a meta-analysis

    PubMed Central

    Zeng, Fangfang; Zhu, Sui; Wong, Martin Chi-Sang; Yang, Zuyao; Tang, Jinling; Li, Keshen; Su, Xuefen

    2016-01-01

    Previous studies have examined the role of three NOS3 gene polymorphisms [G894T, T-786C, and the variable number of tandem repeats 4b/a (VNTR 4b/a)] in the susceptibility to preeclampsia with inconclusive findings. We therefore conducted an updated meta-analysis by including more studies. The most appropriate genetic model was chosen for each polymorphism by using a well-established method. Pooled results indicated that, compared with the GT + GG genotype, the TT genotype of G894T was associated with an increased risk of preeclampsia (odds ratio (OR) = 1.46; 95% confidence interval (CI) = 1.21–1.77, P < 0.001; I2 = 40.2%). The CC genotype of T-786C was also associated with a higher risk of preeclampsia (OR = 1.30; 95% CI = 1.07–1.58, P = 0.034; I2 = 46.9%) than the CT + TT genotype. No association was found for VNTR 4b/a. Stratified analysis indicated that the increased risk was evident for high-quality studies both for G894T and T-786C, and for studies conducted among Caucasians and Africans for T-786C. However, the increased risk for T-786C among Africans needs further confirmation due to the high probability of false-positive reports. Our results suggested that G894T and T-786C polymorphisms, but not VNTR 4b/a, were associated with an increased risk of preeclampsia. PMID:26997284

  1. GACT: a Genome build and Allele definition Conversion Tool for SNP imputation and meta-analysis in genetic association studies

    PubMed Central

    2014-01-01

    Background Genome-wide association studies (GWAS) have successfully identified genes associated with complex human diseases. Although much of the heritability remains unexplained, combining single nucleotide polymorphism (SNP) genotypes from multiple studies for meta-analysis will increase the statistical power to identify new disease-associated variants. Meta-analysis requires same allele definition (nomenclature) and genome build among individual studies. Similarly, imputation, commonly-used prior to meta-analysis, requires the same consistency. However, the genotypes from various GWAS are generated using different genotyping platforms, arrays or SNP-calling approaches, resulting in use of different genome builds and allele definitions. Incorrect assumptions of identical allele definition among combined GWAS lead to a large portion of discarded genotypes or incorrect association findings. There is no published tool that predicts and converts among all major allele definitions. Results In this study, we have developed a tool, GACT, which stands for Genome build and Allele definition Conversion Tool, that predicts and inter-converts between any of the common SNP allele definitions and between the major genome builds. In addition, we assessed several factors that may affect imputation quality, and our results indicated that inclusion of singletons in the reference had detrimental effects while ambiguous SNPs had no measurable effect. Unexpectedly, exclusion of genotypes with missing rate > 0.001 (40% of study SNPs) showed no significant decrease of imputation quality (even significantly higher when compared to the imputation with singletons in the reference), especially for rare SNPs. Conclusion GACT is a new, powerful, and user-friendly tool with both command-line and interactive online versions that can accurately predict, and convert between any of the common allele definitions and between genome builds for genome-wide meta-analysis and imputation of

  2. Dementia risk estimates associated with measures of depression: a systematic review and meta-analysis

    PubMed Central

    Anstey, Kaarin J

    2015-01-01

    Objectives To perform a systematic review of reported HRs of all cause dementia, Alzheimer's disease (AD) and vascular dementia (VaD) for late-life depression and depressive symptomatology on specific screening instruments at specific thresholds. Design Meta-analysis with meta-regression. Setting and participants PubMed, PsycInfo, and Cochrane databases were searched through 28 February 2014. Articles reporting HRs for incident all-cause dementia, AD and VaD based on published clinical criteria using validated measures of clinical depression or symptomatology from prospective studies of general population of adults were selected by consensus among multiple reviewers. Studies that did not use clinical dementia diagnoses or validated instruments for the assessment of depression were excluded. Data were extracted by two reviewers and reviewed by two other independent reviewers. The most specific analyses possible using continuous symptomatology ratings and categorical measures of clinical depression focusing on single instruments with defined reported cut-offs were conducted. Primary outcome measures HRs for all-cause dementia, AD, and VaD were computed where possible for continuous depression scores, or for major depression assessed with single or comparable validated instruments. Results Searches yielded 121 301 articles, of which 36 (0.03%) were eligible. Included studies provided a combined sample size of 66 532 individuals including 6593 cases of dementia, 2797 cases of AD and 585 cases of VaD. The increased risk associated with depression did not significantly differ by type of dementia and ranged from 83% to 104% for diagnostic thresholds consistent with major depression. Risk associated with continuous depression symptomatology measures were consistent with those for clinical thresholds. Conclusions Late-life depression is consistently and similarly associated with a twofold increased risk of dementia. The precise risk estimates produced in this study for

  3. Association between N-acetyltransferase 2 polymorphisms and pancreatic cancer risk: a meta-analysis.

    PubMed

    Liang, J X; Gao, W; Liang, Y; Zhou, X M

    2015-01-01

    N-acetyltransferase 2 (NAT2) is an essential phase II enzyme in the metabolism of aromatic and heterocyclic amines and of hydrazines. NAT2 activity can be divided into three phenotypes: rapid, intermediate, and slow. Studies identifying an association between NAT2 polymorphism and the risk of pancreatic cancer have shown conflicting results. In order to assess this relationship comprehensively, we performed a meta-analysis that involved 1607 patients with pancreatic cancer and 1682 controls from six studies, which were selected from a group of ten, identified by a search of PubMed and Embase databases up to July 2014. Relative risks (RRs) with 95% confidence intervals (CIs) were used to evaluate the relationships. In the overall analysis, no significant associations between NAT2 rapid acetylation genotypes and pancreatic cancer risk (RR = 0.93, 95%CI = 0.73-1.19) were found; however, the results showed significant heterogeneity (I2 = 55.0%). The results from subgroup analysis suggested that the rapid genotypes might decrease the risk of pancreatic cancer (RR = 0.56, 95%CI = 0.38-0.84) in Turkey, although the association was not significant in the United States population (RR = 0.97, 95%CI = 0.71-1.34) or in the multi-center studies (RR = 1.10, 95%CI = 0.90-1.34). Analysis of the slow acetylation genotypes demonstrated the converse outcomes. In conclusion, the results of our study suggested that the NAT2 slow acetylation genotypes might increase the susceptibility to pancreatic cancer in Europe but that these have no significant effects in the United States and multi-center populations. PMID:26681215

  4. A genome-wide meta-analysis of association studies of Cloninger's Temperament Scales

    PubMed Central

    Service, S K; Verweij, K J H; Lahti, J; Congdon, E; Ekelund, J; Hintsanen, M; Räikkönen, K; Lehtimäki, T; Kähönen, M; Widen, E; Taanila, A; Veijola, J; Heath, A C; Madden, P A F; Montgomery, G W; Sabatti, C; Järvelin, M-R; Palotie, A; Raitakari, O; Viikari, J; Martin, N G; Eriksson, J G; Keltikangas-Järvinen, L; Wray, N R; Freimer, N B

    2012-01-01

    Temperament has a strongly heritable component, yet multiple independent genome-wide studies have failed to identify significant genetic associations. We have assembled the largest sample to date of persons with genome-wide genotype data, who have been assessed with Cloninger's Temperament and Character Inventory. Sum scores for novelty seeking, harm avoidance, reward dependence and persistence have been measured in over 11 000 persons collected in four different cohorts. Our study had >80% power to identify genome-wide significant loci (P<1.25 × 10−8, with correction for testing four scales) accounting for ⩾0.4% of the phenotypic variance in temperament scales. Using meta-analysis techniques, gene-based tests and pathway analysis we have tested over 1.2 million single-nucleotide polymorphisms (SNPs) for association to each of the four temperament dimensions. We did not discover any SNPs, genes, or pathways to be significantly related to the four temperament dimensions, after correcting for multiple testing. Less than 1% of the variability in any temperament dimension appears to be accounted for by a risk score derived from the SNPs showing strongest association to the temperament dimensions. Elucidation of genetic loci significantly influencing temperament and personality will require potentially very large samples, and/or a more refined phenotype. Item response theory methodology may be a way to incorporate data from cohorts assessed with multiple personality instruments, and might be a method by which a large sample of a more refined phenotype could be acquired. PMID:22832960

  5. The Association between Metabolic Syndrome and Hepatocellular carcinoma: Systemic Review and Meta-Analysis

    PubMed Central

    Jinjuvadia, Raxitkumar; Patel, Suhag; Liangpunsakul, Suthat

    2013-01-01

    Background The Metabolic syndrome (MetS) and/or its individual components have been linked to the development of cancer. Recent studies have suggested a similar link to hepatocellular carcinoma (HCC). The aim of this study was to evaluate the direction and magnitude of the association between the MetS and HCC. Methods Two reviewers independently conducted a systemic search to identify available evidence from databases from January 1980 to June 2012. Search terms included ‘Metabolic syndrome’, ‘insulin resistance syndrome’, ‘metabolic abnormalities’ combined with ‘hepatocellular carcinoma’ and ‘liver cancer’. No language restriction was applied to the search. Only studies reporting an effect measure for the association between MetS and HCC were eligible for inclusion. Publication bias was assessed using the Begg and Egger’s tests, with a visual inspection of funnel plot. All analyses were performed using Comprehensive Meta-Analysis version 2 software. Results Four studies (3 cohort and 1 case-control) with a total of 829,651 participants were included in the analysis. The age range of participants was between 30 and 84 years. The combined analysis showed an overall 81% increase risk of HCC in cases with MetS (RR: 1.81, 95% CI: 1.37–2.41). After excluding the single case-control study from analysis, the overall risk ratio remained statistically significant (RR: 1.49, 95% CI: 1.27–1.74). Funnel plot inspection, Begg and Egger’s tests showed no evidence of publication bias for combined analysis. Conclusions Though studies are scarce, currently available epidemiologic data is suggestive of significantly higher risk of hepatocellular carcinoma among patients with metabolic syndrome. PMID:24402120

  6. The Association Between Atopy and Childhood/Adolescent Leukemia: A Meta-Analysis

    PubMed Central

    Linabery, Amy M.; Jurek, Anne M.; Duval, Sue; Ross, Julie A.

    2010-01-01

    Atopic disease is hypothesized to be protective against several malignancies, including childhood/adolescent leukemia. To summarize the available epidemiologic evidence, the authors performed a meta-analysis of associations between atopy/allergies, asthma, eczema, hay fever, and hives and childhood/adolescent leukemia, acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). They searched MEDLINE literature (1952–March 2009) and queried international experts to identify eligible studies. Ten case-control studies were included. Summary odds ratios and 95% confidence intervals were computed via random-effects models. Odds ratios for atopy/allergies were 1.42 (95% confidence interval (CI): 0.60, 3.35) for 3 studies of leukemia overall, 0.69 (95% CI: 0.54, 0.89) for 6 studies of ALL, and 0.87 (95% CI: 0.62, 1.22) for 2 studies of AML, with high levels of heterogeneity detected for leukemia overall and ALL. Inverse associations were observed for ALL and asthma (odds ratio (OR) = 0.79, 95% CI: 0.61, 1.02), eczema (OR = 0.74, 95% CI: 0.58, 0.96), and hay fever (OR = 0.55, 95% CI: 0.46, 0.66) examined separately. Odds ratios for ALL differed by study design, exposure data source, and latency period, indicating that these factors affect study results. These results should be interpreted cautiously given the modest number of studies, substantial heterogeneity, and potential exposure misclassification but are useful in designing future research. PMID:20228139

  7. Drug-Induced Reduction in Albuminuria Is Associated with Subsequent Renoprotection: A Meta-Analysis

    PubMed Central

    Kröpelin, Tobias F.; Hoekman, Jarno; de Zeeuw, Dick

    2015-01-01

    Albuminuria has been proposed as a surrogate end point in randomized clinical trials of renal disease progression. Most evidence comes from observational analyses showing that treatment-induced short-term changes in albuminuria correlate with risk change for ESRD. However, such studies are prone to selection bias and residual confounding. To minimize this bias, we performed a meta-analysis of clinical trials to correlate the placebo-corrected drug effect on albuminuria and ESRD to more reliably delineate the association between changes in albuminuria and ESRD. MEDLINE and EMBASE were searched for clinical trials reported between 1950 and April 2014. Included trials had a mean follow-up of ≥1000 patient-years, reported ESRD outcomes, and measured albuminuria at baseline and during follow-up. Twenty-one clinical trials involving 78,342 patients and 4183 ESRD events were included. Median time to first albuminuria measurement was 6 months. Fourteen trials tested the effect of renin-angiotensin-aldosterone-system inhibitors and seven trials tested other interventions. We observed variability across trials in the treatment effect on albuminuria (range, −1.3% to −32.1%) and ESRD (range, −55% to +35% risk change). Meta-regression analysis revealed that the placebo-adjusted treatment effect on albuminuria significantly correlated with the treatment effect on ESRD: for each 30% reduction in albuminuria, the risk of ESRD decreased by 23.7% (95% confidence interval, 11.4% to 34.2%; P=0.001). The association was consistent regardless of drug class (P=0.73) or other patient or trial characteristics. These findings suggest albuminuria may be a valid substitute for ESRD in many circumstances, even taking into account possible other drug-specific effects that may alter renal outcomes. PMID:25421558

  8. Compare and Contrast Meta Analysis (CCMA): A Method for Identification of Pleiotropic Loci in Genome-Wide Association Studies

    PubMed Central

    Baurecht, Hansjörg; Hotze, Melanie; Rodríguez, Elke; Manz, Judith; Weidinger, Stephan; Cordell, Heather J.

    2016-01-01

    In recent years, genome-wide association studies (GWAS) have identified many loci that are shared among common disorders and this has raised interest in pleiotropy. For performing appropriate analysis, several methods have been proposed, e.g. conducting a look-up in external sources or exploiting GWAS results by meta-analysis based methods. We recently proposed the Compare & Contrast Meta-Analysis (CCMA) approach where significance thresholds were obtained by simulation. Here we present analytical formulae for the density and cumulative distribution function of the CCMA test statistic under the null hypothesis of no pleiotropy and no association, which, conveniently for practical reasons, turns out to be exponentially distributed. This allows researchers to apply the CCMA method without having to rely on simulations. Finally, we show that CCMA demonstrates power to detect disease-specific, agonistic and antagonistic loci comparable to the frequently used Subset-Based Meta-Analysis approach, while better controlling the type I error rate. PMID:27149374

  9. Prevention of Central Line–Associated Bloodstream Infections Through Quality Improvement Interventions: A Systematic Review and Meta-analysis

    PubMed Central

    Perl, Trish M.; Blot, Koen; Bergs, Jochen; Vogelaers, Dirk; Blot, Stijn; Vandijck, Dominique

    2014-01-01

    This systematic review and meta-analysis examines the impact of quality improvement interventions on central line–associated bloodstream infections in adult intensive care units. Studies were identified through Medline and manual searches (1995–June 2012). Random-effects meta-analysis obtained pooled odds ratios (ORs) and 95% confidence intervals (CIs). Meta-regression assessed the impact of bundle/checklist interventions and high baseline rates on intervention effect. Forty-one before–after studies identified an infection rate decrease (OR, 0.39 [95% CI, .33–.46]; P < .001). This effect was more pronounced for trials implementing a bundle or checklist approach (P = .03). Furthermore, meta-analysis of 6 interrupted time series studies revealed an infection rate reduction 3 months postintervention (OR, 0.30 [95% CI, .10–.88]; P = .03). There was no difference in infection rates between studies with low or high baseline rates (P = .18). These results suggest that quality improvement interventions contribute to the prevention of central line–associated bloodstream infections. Implementation of care bundles and checklists appears to yield stronger risk reductions. PMID:24723276

  10. Negative association between androgen receptor gene CAG repeat polymorphism and polycystic ovary syndrome? A systematic review and meta-analysis

    PubMed Central

    Wang, Rui; Goodarzi, Mark O.; Xiong, Ting; Wang, Di; Azziz, Ricardo; Zhang, Hanwang

    2012-01-01

    A number of studies focusing on the association between the exon 1 CAG repeat polymorphism of the androgen receptor (AR) gene and polycystic ovary syndrome (PCOS) have revealed conflicting results. The current systematic review and meta-analysis was conducted to quantify the strength of the association and to explore potential sources of heterogeneity that may have influenced the results. Studies matched to search terms from PubMed, EMBASE and HuGE Navigator published through to 31 January 2012 were retrieved. Data extraction from the included studies was carried out by two authors independently. Weighted mean differences (WMDs) of biallelic mean and odds ratios (ORs) of alleles and genotypes were pooled for meta-analysis. Sixteen articles reporting on 17 studies were included. In continuous data analysis, the summary WMD was −0.06 (95% confidence interval −0.29 to 0.16). In dichotomous data analysis, we divided the alleles into short and long alleles and calculated the summary ORs. No statistically significant results were identified by different comparison models or different cut-off point definitions. No publication bias was observed in continuous and dichotomous data analysis. In summary, the current systematic review and meta-analysis found that the AR CAG microsatellite repeat polymorphism is unlikely to be a major determining factor in the development of PCOS. PMID:22695532

  11. Career Benefits Associated with Mentoring for Mentors: A Meta-Analysis

    ERIC Educational Resources Information Center

    Ghosh, Rajashi; Reio, Thomas G., Jr.

    2013-01-01

    Mentoring has been studied extensively as it is linked to protege career development and growth. Recent mentoring research is beginning to acknowledge however that mentors also can accrue substantial benefits from mentoring. A meta-analysis was conducted where the provision of career, psychosocial and role modeling mentoring support were…

  12. Meta-analysis of genome-wide association studies for circulating phylloquinone concentrations12345

    PubMed Central

    Dashti, Hassan S; Shea, M Kyla; Smith, Caren E; Tanaka, Toshiko; Hruby, Adela; Richardson, Kris; Wang, Thomas J; Nalls, Mike A; Guo, Xiuqing; Liu, Yongmei; Yao, Jie; Li, Dalin; Johnson, W Craig; Benjamin, Emelia J; Kritchevsky, Stephen B; Siscovick, David S; Ordovás, José M

    2014-01-01

    Background: Poor vitamin K status is linked to greater risk of several chronic diseases. Age, sex, and diet are determinants of circulating vitamin K; however, there is still large unexplained interindividual variability in vitamin K status. Although a strong genetic component has been hypothesized, this has yet to be examined by a genome-wide association (GWA) study. Objective: The objective was to identify common genetic variants associated with concentrations of circulating phylloquinone, the primary circulating form of vitamin K. Design: We conducted a 2-stage GWA meta-analysis of circulating phylloquinone in 2 populations of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium Nutrition Working Group. Circulating phylloquinone was measured by using reversed-phase high-performance liquid chromatography. Results from adjusted cohort-specific discovery GWA analyses were meta-analyzed with inverse variance weights (n = 2138). Associations with circulating phylloquinone at P < 1 × 10−6 were then evaluated in a second-stage analysis consisting of one independent cohort (n = 265). Results: No significant association was observed for circulating phylloquinone at the genome-wide significance level of 5 × 10−8. However, from the discovery GWA, there were 11 single-nucleotide polymorphism (SNP) associations with circulating phylloquinone at P < 1 × 10−6, including a functional variant previously associated with warfarin dose and altered phylloquinone metabolism. These SNPs are on 5 independent loci on 11q23.3, 8q24.3, 5q22.3, 2p12, and 19p13.12, and they fall within or near the candidate genes APOA1/C3/A4/A5 cluster (involved in lipoprotein metabolism), COL22A1, CDO1, CTNAA2, and CYP4F2 (a phylloquinone oxidase), respectively. Second-stage analysis in an independent cohort further suggests the association of the 5q22.3 locus with circulating phylloquinone (P < 0.05). Conclusions: Multiple candidate genes related to

  13. Metformin for Clozapine Associated Obesity: A Systematic Review and Meta-Analysis

    PubMed Central

    Leung, Janni; Russell, Anthony W.; Wysoczanski, Daniel; Kisely, Steve

    2016-01-01

    Background Although clozapine is the gold-standard for treatment refractory schizophrenia, it has the worst metabolic profile of all antipsychotics. This is partly mediated by clozapine’s impact on glucagon-like peptide (GLP-1). There is an absence of robust evidence for effective treatments for clozapine associated weight gain and metabolic syndrome. Metformin, with its role in increasing GLP-1 may aid weight loss among people on clozapine. Methods We conducted a systematic-review and meta-analysis of metformin versus placebo for change in weight and metabolic syndrome for people on clozapine without diabetes mellitus. We searched the Cochrane Schizophrenia Group’s trial register, Pubmed and Embase, as well as the following Chinese databases: the Chinese Biomedical Literature Service System and China Knowledge Resource Integrated Database. This was supplemented by hand searches of key papers. Results Eight studies, of which three were from Chinese databases, with 478 participants were included. We found that metformin was superior to placebo in terms of weight loss (-3.12kg, 95%CI -4.88kg to -1.37kg) and BMI (-1.18kg/m2, 95%CI -1.76kg/m2 to -0.61kg/m2). Metformin significantly improved three of the five components of metabolic syndrome; waist circumference, fasting glucose and triglycerides. Sensitivity analysis on study quality and duration did not greatly impact results. Conclusions Metformin led to clinically meaningful weight loss among people on clozapine, and may reduce the rates of metabolic syndrome. Inclusion of metformin into the treatment protocols of people on clozapine, as tolerated, should be considered. Trial Registration PROSPERO registration number: CRD42015029723 PMID:27304831

  14. Meta-Analysis for the Association between Polymorphisms in Interleukin-17A and Risk of Coronary Artery Disease

    PubMed Central

    Bao, Mei-Hua; Luo, Huai-Qing; Xiang, Ju; Tang, Liang; Dong, Li-Ping; Li, Guang-Yi; Zeng, Jie; Li, Jian-Ming

    2016-01-01

    Coronary artery disease (CAD) is a disease which has become a leading cause of death worldwide. The polymorphisms in Interleukin-17 (IL-17A), including rs2275913, rs3819024, rs3819025, rs3748067, rs8193037, rs4711998, and rs8193036, have been found to be probably associated with the risk of CAD. However, the results were inconsistent and inconclusive. The present study performed a meta-analysis to get a more precise and comprehensive estimation of the association between the IL-17A polymorphisms and CAD risk. The Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Databases were searched for related studies. A total of six studies, including 3542 cases and 3212 controls, were identified for the meta-analysis. The main findings of the present meta-analysis show that the TT genotype of IL-17A rs3748067 is associated with a significant lower risk of CAD in the homozygous model odds ratio (OR) (OR = 0.37) in Asians. No significant association was found for rs2275913, rs3819024, rs3819025, rs8193037, rs4711998, and rs8193036 with CAD susceptibility in the overall analysis. However, subgroup analysis indicated a significant decreased risk of CAD for the GG genotype and G allele of rs2275913 in a small sample size group, and a higher risk of CAD for the GG genotype and G allele of rs8193037 in a heterozygous model (OR = 1.56), dominant model (OR = 1.54), and allelic model (OR = 1.47) in Asians. In conclusion, the current meta-analysis suggests a significant relationship between rs3748067, rs8193037, and CAD in Asians, while for rs2275913, rs3819024, rs3819025, rs4711998, rs8193036, no such relations were found. Thus, IL-17A rs3748067 and rs8193037 might be recommended as a predictor for susceptibility of CAD for Asians. However, the results of this meta-analysis are hypothesis-generating results which should be interpreted with caution because of the heterogeneity and publication bias

  15. Meta-Analysis for the Association between Polymorphisms in Interleukin-17A and Risk of Coronary Artery Disease.

    PubMed

    Bao, Mei-Hua; Luo, Huai-Qing; Xiang, Ju; Tang, Liang; Dong, Li-Ping; Li, Guang-Yi; Zeng, Jie; Li, Jian-Ming

    2016-01-01

    Coronary artery disease (CAD) is a disease which has become a leading cause of death worldwide. The polymorphisms in Interleukin-17 (IL-17A), including rs2275913, rs3819024, rs3819025, rs3748067, rs8193037, rs4711998, and rs8193036, have been found to be probably associated with the risk of CAD. However, the results were inconsistent and inconclusive. The present study performed a meta-analysis to get a more precise and comprehensive estimation of the association between the IL-17A polymorphisms and CAD risk. The Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Databases were searched for related studies. A total of six studies, including 3542 cases and 3212 controls, were identified for the meta-analysis. The main findings of the present meta-analysis show that the TT genotype of IL-17A rs3748067 is associated with a significant lower risk of CAD in the homozygous model odds ratio (OR) (OR = 0.37) in Asians. No significant association was found for rs2275913, rs3819024, rs3819025, rs8193037, rs4711998, and rs8193036 with CAD susceptibility in the overall analysis. However, subgroup analysis indicated a significant decreased risk of CAD for the GG genotype and G allele of rs2275913 in a small sample size group, and a higher risk of CAD for the GG genotype and G allele of rs8193037 in a heterozygous model (OR = 1.56), dominant model (OR = 1.54), and allelic model (OR = 1.47) in Asians. In conclusion, the current meta-analysis suggests a significant relationship between rs3748067, rs8193037, and CAD in Asians, while for rs2275913, rs3819024, rs3819025, rs4711998, rs8193036, no such relations were found. Thus, IL-17A rs3748067 and rs8193037 might be recommended as a predictor for susceptibility of CAD for Asians. However, the results of this meta-analysis are hypothesis-generating results which should be interpreted with caution because of the heterogeneity and publication bias

  16. Hippocampal Gene Expression Meta-Analysis Identifies Aging and Age-Associated Spatial Learning Impairment (ASLI) Genes and Pathways

    PubMed Central

    Uddin, Raihan K.; Singh, Shiva M.

    2013-01-01

    A number of gene expression microarray studies have been carried out in the past, which studied aging and age-associated spatial learning impairment (ASLI) in the hippocampus in animal models, with varying results. Data from such studies were never integrated to identify the most significant ASLI genes and to understand their effect. In this study we integrated these data involving rats using meta-analysis. Our results show that proper removal of batch effects from microarray data generated from different laboratories is necessary before integrating them for meta-analysis. Our meta-analysis has identified a number of significant differentially expressed genes across age or across ASLI. These genes affect many key functions in the aged compared to the young rats, which include viability of neurons, cell-to-cell signalling and interaction, migration of cells, neuronal growth, and synaptic plasticity. These functional changes due to the altered gene expression may manifest into various neurodegenerative diseases and disorders, some of which leading into syndromic memory impairments. While other aging related molecular changes can result into altered synaptic plasticity simply causing normal aging related non-syndromic learning or spatial learning impairments such as ASLI. PMID:23874995

  17. Association between ABCB1 polymorphisms and haplotypes and Alzheimer’s disease: a meta-analysis

    PubMed Central

    Zhong, Xin; Liu, Ming-Yan; Sun, Xiao-Hong; Wei, Min-Jie

    2016-01-01

    Although several epidemiological studies have investigated the association between ATP-binding cassette subfamily B member 1 (ABCB1) gene polymorphisms and Alzheimer’s disease (AD) susceptibility, controversial results exist. Here, we performed a meta-analysis to assess whether ABCB1 polymorphisms 3435C > T (rs1045642), 2677G > T/A (rs2032582), 1236C > T (rs1128503) and haplotypes were associated with AD risk. Nine independent publications were included and analyzed. Crude odds ratio (OR) and 95% confidence interval (CI) were applied to investigate the strength of the association. Sensitivity analysis was conducted to measure the robustness of our analysis. A funnel plot and trim and fill method were used to test and adjust for publication bias. The results showed a significant association between the 3435C > T single nucleotide polymorphism (SNP) and AD susceptibility (CT vs. CC: OR = 1.24, 95% CI = 1.06–1.45, P = 0.01; CT + TT vs. CC: OR = 1.21, 95% CI = 1.04–1.41, P = 0.01) in the total population, as well as in Caucasian subgroup. The 2677G > T/A SNP was related to a decreased AD risk in Caucasian subgroup (TT + TA + AA vs. GT + GA + GG: OR = 0.68, 95% CI = 0.47–0.98, P = 0.04). Moreover, the ABCB1 haplotype analysis showed that the 1236T/2677T/3435C haplotype was associated with a higher risk of AD (OR = 1.99, 95% CI = 1.24–3.18, P = 0.00). Our results suggest that the ABCB1 3435C > T SNP, the 2677G > T/A SNP and 1236T/2677T/3435C haplotype are significantly associated with AD susceptibility. PMID:27600024

  18. Association between ABCB1 polymorphisms and haplotypes and Alzheimer's disease: a meta-analysis.

    PubMed

    Zhong, Xin; Liu, Ming-Yan; Sun, Xiao-Hong; Wei, Min-Jie

    2016-01-01

    Although several epidemiological studies have investigated the association between ATP-binding cassette subfamily B member 1 (ABCB1) gene polymorphisms and Alzheimer's disease (AD) susceptibility, controversial results exist. Here, we performed a meta-analysis to assess whether ABCB1 polymorphisms 3435C > T (rs1045642), 2677G > T/A (rs2032582), 1236C > T (rs1128503) and haplotypes were associated with AD risk. Nine independent publications were included and analyzed. Crude odds ratio (OR) and 95% confidence interval (CI) were applied to investigate the strength of the association. Sensitivity analysis was conducted to measure the robustness of our analysis. A funnel plot and trim and fill method were used to test and adjust for publication bias. The results showed a significant association between the 3435C > T single nucleotide polymorphism (SNP) and AD susceptibility (CT vs. CC: OR = 1.24, 95% CI = 1.06-1.45, P = 0.01; CT + TT vs. CC: OR = 1.21, 95% CI = 1.04-1.41, P = 0.01) in the total population, as well as in Caucasian subgroup. The 2677G > T/A SNP was related to a decreased AD risk in Caucasian subgroup (TT + TA + AA vs. GT + GA + GG: OR = 0.68, 95% CI = 0.47-0.98, P = 0.04). Moreover, the ABCB1 haplotype analysis showed that the 1236T/2677T/3435C haplotype was associated with a higher risk of AD (OR = 1.99, 95% CI = 1.24-3.18, P = 0.00). Our results suggest that the ABCB1 3435C > T SNP, the 2677G > T/A SNP and 1236T/2677T/3435C haplotype are significantly associated with AD susceptibility. PMID:27600024

  19. Association of PAEs with Precocious Puberty in Children: A Systematic Review and Meta-Analysis

    PubMed Central

    Wen, Yi; Liu, Shu-Dan; Lei, Xun; Ling, Yu-Shuang; Luo, Yan; Liu, Qin

    2015-01-01

    Background: Precocious puberty (PP) currently affects 1 in 5000 children and is 10 times more common in girls. Existing studies have tried to detect an association between phathalic acid esters (PAEs) and PP, but the results did not reach a consensus. Objective: To estimate the association between PAEs and children with PP based on current evidence. Methods: Databases including PubMed (1978 to March 2015), OVID (1946 to March 2015), Web of Science (1970 to March 2015), EBSCO (1976 to March 2015), CNKI (1979 to March 2015), WANFANG DATA (1987 to March 2015), CBM (1978 to March 2015) and CQVIP (1989 to March 2015) were searched to identify all case-control studies that determined the exposure and concentration of PAEs and their metabolites in children with PP. Meta-analysis of the pooled standard mean difference (SMD) and odds ratio (OR) with 95% confidence intervals (CI) were calculated. Results: A total of 14 studies involving 2223 subjects were finally included. The pooled estimates showed that PP was associated with di-(2-ethylhexyl)-phthalate (DEHP) exposure (OR: 3.90, 95% CI: 2.77 to 5.49). Besides, the concentration of DEHP (SMD: 1.73, 95% CI: 0.54 to 2.91) and di-n-butyl phthalate (DBP) (SMD: 4.31, 95% CI: 2.67 to 5.95) in the PP group were significantly higher than those in the control group, respectively, while no difference was detected between case and control groups in either serum or urinary concentration of mono-(2-ethylhexyl)-phthalate (MEHP), monobutyl phthalate (MBP), mono(2-ethyl-5-oxohexyl) phthalate(MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), monomethyl phthalate (MMP), monobenzyl phthalate (MBzP) or monoethyl phthalate (MEP). Conclusions: Exposure of DEHP and DBP might be associated with PP risk for girls, however, there is no evidence to show an association between the exposure to most PAE metabolites and PP. Given the moderate strength of the results, well-designed cohort studies with large sample size should be performed in

  20. Assessment of Osteoarthritis Candidate Genes in a Meta-Analysis of Nine Genome-Wide Association Studies

    PubMed Central

    Rodriguez-Fontenla, Cristina; Calaza, Manuel; Evangelou, Evangelos; Valdes, Ana M; Arden, Nigel; Blanco, Francisco J; Carr, Andrew; Chapman, Kay; Deloukas, Panos; Doherty, Michael; Esko, Tõnu; Garcés Aletá, Carlos M; Gomez-Reino Carnota, Juan J; Helgadottir, Hafdis; Hofman, Albert; Jonsdottir, Ingileif; Kerkhof, Hanneke J M; Kloppenburg, Margreet; McCaskie, Andrew; Ntzani, Evangelia E; Ollier, William E R; Oreiro, Natividad; Panoutsopoulou, Kalliope; Ralston, Stuart H; Ramos, Yolande F; Riancho, Jose A; Rivadeneira, Fernando; Slagboom, P Eline; Styrkarsdottir, Unnur; Thorsteinsdottir, Unnur; Thorleifsson, Gudmar; Tsezou, Aspasia; Uitterlinden, André G; Wallis, Gillian A; Wilkinson, J Mark; Zhai, Guangju; Zhu, Yanyan; Felson, David T; Ioannidis, John P A; Loughlin, John; Metspalu, Andres; Meulenbelt, Ingrid; Stefansson, Kari; van Meurs, Joyce B; Zeggini, Eleftheria; Spector, Timothy D; Gonzalez, Antonio

    2014-01-01

    Objective To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA. Methods A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) Navigator. All of their single-nucleotide polymorphisms (SNPs) with an allele frequency of >5% were assessed by fixed-effects meta-analysis of 9 genome-wide association studies (GWAS) that included 5,636 patients with knee OA and 16,972 control subjects and 4,349 patients with hip OA and 17,836 control subjects of European ancestry. An additional 5,921 individuals were genotyped for significantly associated SNPs in the meta-analysis. After correction for the number of independent tests, P values less than 1.58 × 10−5 were considered significant. Results SNPs at only 2 of the 199 candidate genes (COL11A1 and VEGF) were associated with OA in the meta-analysis. Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 × 10−5, odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06−1.17) and rs1241164 (P = 1.47 × 10−5, OR 0.82, 95% CI 0.74−0.89). The sex-stratified analysis also showed association of COL11A1 SNP rs4908291 in women (P = 1.29 × 10−5, OR 0.87, 95% CI 0.82−0.92); this SNP showed linkage disequilibrium with rs4907986. A single SNP of VEGF, rs833058, showed association with hip OA in men (P = 1.35 × 10−5, OR 0.85, 95% CI 0.79−0.91). After additional samples were genotyped, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened. Conclusion Two candidate genes, COL11A1 and VEGF, were significantly associated with OA in this focused meta-analysis. The remaining candidate genes were not associated. PMID:24757145

  1. Association of osteopontin polymorphism with cancer risk: a meta-analysis

    PubMed Central

    Yang, Gang; Peng, Xiaoxing; Guo, Pengju; Yang, Ge

    2015-01-01

    To investigate the association of osteopontin gene -443 C>T, -156 G>GG, and -1748 A>G polymorphisms with cancer risk. The Medline, PubMed, PUBMED, EMBASE and Web of Science databases were searched. Meta-analyses were conducted using RevMan 5.2 software. After searching and evaluating the included papers, total 10 documents involved in -443 C>T, 8 papers involved in four articles involved in -156 G>GG and -1748 A>G were included into this meta analysis. There were no significant differences in genotype osteopontin -443 C>T distribution between cancer cases and control (OR=0.98, 95% CI=0.68-1.40, P=0.90; OR=0.90, 95% CI=0.60-1.35, P=0.62; OR=0.98, 95% CI=0.59-1.64, P=0.94; OR=0.87, 95% CI=0.60-1.25, P=0.44, respectively). Meanwhile, no association between osteopontin -1748 A>G polymorphism and tumors under all genetic models. (OR=0.73, 95% CI=0.54-1.00, P=0.05; OR=0.95, 95% CI=0.82-1.10, P=0.48; OR=1.31, 95% CI=0.95-1.81, P=0.10; OR=0.90, 95% CI=0.77-1.06, P=0.20, respectively). However, osteopontin -156 G>GG polymorphism is only partly related to the tumor risk. (GGGG+GGG vs GG model, OR=1.21, 95% CI=1.01-1.46, P=0.04; GGG vs GG model: OR=1.19, 95% CI=1.05-1.35, P=0.008, respectively) osteopontin gene polymorphisms, -443 C>T and -1748 A>G was not associated with cancer risk, but partly associated to tumor risk for -156 G>GG gene polymorphism. PMID:26885018

  2. Association between BRIP1 (BACH1) polymorphisms and breast cancer risk: a meta-analysis.

    PubMed

    Pabalan, Noel; Jarjanazi, Hamdi; Ozcelik, Hilmi

    2013-01-01

    Inconsistency of reported associations between the Pro919Ser polymorphism in the BRCA1 interacting protein 1 (BRIP1) gene and breast cancer prompted us to undertake a meta-analysis. Although investigated by fewer studies, we have also studied the risk associated with the two additional BRIP1 polymorphisms, C47G and G64A, and breast cancer riskWe conducted searches of the published literature in MEDLINE through PubMed up to October 2012. Individual data on 5,122 cases and 5,735 controls from eight published case-control studies were evaluated for the Pro919Ser polymorphism. Accordingly, C47G and G64A polymorphisms were studied in 1,539 cases and 1,183 controls, and 667 and 782, respectively.In the overall analysis, association was lacking between the Pro919Ser polymorphism and breast cancer risk (odds ratio [OR] 0.98-1.02), materially unchanged when confined to subjects of European ancestry (OR 0.96-1.03) or even in the high-powered studies (OR 0.97-1.03). In the menopausal subgroups, premenopausal women followed the null pattern (OR 0.94-0.98) for the Pro and Ser allele contrasts, but not for the Pro-Ser genotype comparison where significant increased risk was observed (OR 1.39, P = 0.002). The postmenopausal women (>50 years) exhibited a range of pooled effects from protection (OR 0.83, P = 0.11) in the Pro-Ser genotype to slightly increased risk (OR 1.12-1.16, P = 0.28-0.42) in the Pro and Ser allele comparisons. The G64A polymorphism effects were essentially null (OR 0.90-0.98), but C47G was found to confer non-significantly increased risk under all genetic models (OR 1.27-1.40).Upon conclusion, overall summary estimates imply no associations but suggest susceptibility among carriers of the C47G polymorphism and Pro-Ser genotype in premenopausal women. The premenopausal findings and variable outcomes in postmenopausal women require more studies for confirmation. PMID:23225146

  3. Association between BHMT gene rs3733890 polymorphism and cancer risk: evidence from a meta-analysis

    PubMed Central

    Xu, Yue; Yan, Cunye; Hao, Zongyao; Zhou, Jun; Fan, Song; Tai, Sheng; Yang, Cheng; Zhang, Li; Liang, Chaozhao

    2016-01-01

    Background and objective The gene betaine-homocysteine methyltransferase (BHMT) has drawn much attention during the past decades. An increasing number of clinical and genetic investigations have supposed that BHMT rs3733890 polymorphism might be associated with risk of breast cancer and ovarian cancer. As no consistent conclusion has been achieved, we conducted an up-to-date summary of BHMT rs3733890 polymorphism and cancer risk through a meta-analysis. Materials and methods The articles were collected from PubMed, Google Scholar, and CNKI (Chinese) databases up to December 2015. Then, the correlations were determined by reading the titles and abstracts and by further reading the full text to filter the unqualified articles. Odds ratio (OR) and the corresponding 95% confidence intervals (CI) were used to assess the results. Results Among 187 articles collected in the analysis, seven studies with a total of 2,832 cases and 3,958 controls were included for evaluation of the association between BHMT rs3733890 polymorphism and susceptibility of cancer risk. The heterogeneity test showed no significant differences. Furthermore, we found that BHMT −742G>A polymorphism in case and control groups showed no statistically significant association with susceptibility in various cancer types except for uterine cervical cancer (A vs G: OR =0.641, 95% CI =0.445–0.923, P=0.017; AA+AG vs GG: OR =0.579, 95% CI =0.362–0.924, P=0.022). In addition, no statistically significant association was uncovered when stratification analyses were conducted by ethnicity and genotyping methods. Conclusion Our results have shown no obvious evidence that rs3733890 polymorphism in BHMT gene affected the susceptibility of head and neck squamous cell carcinoma, breast cancer, ovarian cancer, colorectal adenoma, and liver cancer. In contrast, we found the protective role of BHMT −742G>A polymorphism in uterine cervical cancer incidence. Future well-designed studies comprising larger sample size

  4. An updated meta-analysis of the association between SORL1 variants and the risk for sporadic Alzheimer's disease.

    PubMed

    Jin, Chunhui; Liu, Xiaowei; Zhang, Fuquan; Wu, Yue; Yuan, Jianmin; Zhu, Jianzhong; Zhang, Feng; Wang, Guoqiang; Cheng, Zaohuo

    2013-01-01

    The pathogenetic mechanism of Alzheimer's disease (AD) is still unknown; however, genetic variants play a critical role in the pathogenesis of AD. It has been reported that single nucleotide polymorphisms (SNPs) of the sortilin-related receptor with A-type repeats (SORL1, also called LR11 or sorLA) are associated with late-onset AD in Caucasian populations. Subsequently, other researchers have attempted to validate this finding in different ethnic populations. However, these findings have produced both negative and positive results. To derive a more precise estimation of whether SORL1 variants are associated with sporadic AD (SAD), we performed the meta-analysis presented in this manuscript. Databases including PubMed, AlzGene, the China National Knowledge Infrastructure (CNKI), and Wan Fang were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association studies. A total of twenty-three case-control studies involving 11,837 cases and 20,022 controls were included. Among the eleven candidate SNPs highlighted in the previous study, four SNPs (SNP 4, SNP 5, SNP 8 and SNP 10) showed a significant association with SAD using a generalized odds ratio (ORG, a model-free approach) and linkage disequilibrium structure analysis. Meanwhile, no significant heterogeneity between the Caucasian and Asian populations for the associated SNPs was observed in the current meta-analysis. Moreover, we further confirmed that the SORL1 three-marker haplotype C-G-C at SNP 8-SNP 9-SNP 10 was significantly associated with SAD (OR = 1.37, 95% CI = 1.12-1.66, padj = 0.008). The current meta-analysis further supports the previous findings that the SORL1 gene may be associated with SAD risk. PMID:23948893

  5. The Association between MTHFR Gene Polymorphisms and Hepatocellular Carcinoma Risk: A Meta-Analysis

    PubMed Central

    Deng, Yan; Huang, Shan; Xu, Juanjuan; Li, Haiwei; Li, Shan; Zhao, Jinmin

    2013-01-01

    Background The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hepatocellular carcinoma (HCC) risk was inconsistent and underpowered. To clarify the effects of MTHFR gene polymorphisms on the risk of HCC, a meta-analysis of all available studies relating C677T and/or A1298C polymorphisms of MTHFR gene to the risk of HCC was conducted. Methods The authors searched PubMed, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Literature database (CBM) for the period up to July 2012. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity. Results Finally, 12 studies with 2,351 cases and 4,091 controls were included for C677T polymorphism and 6 studies with 1,333 cases and 1,878 controls were included for A1298C polymorphism. With respect to A1298C polymorphism, significantly decreased HCC risk was found in the overall population (CC vs. AA: OR = 0.660, 95%CI 0.460–0.946, P = 0.024; recessive model: OR = 0.667, 95%CI = 0.470–0.948, P = 0.024). In subgroup analyses, significantly decreased HCC risk was found in Asian population (CC vs. AA: OR = 0.647, 95%CI = 0.435–0.963; P = 0.032) and population-based studies (CC vs. AA: OR = 0.519, 95%CI = 0.327–0.823; P = 0.005). With respect to C677T polymorphism, no significant association with HCC risk was demonstrated in overall and stratified analyses. Conclusions We concluded that MTHFR A1298C polymorphism may play a protective role in the carcinogenesis of HCC. Further large and well-designed studies are needed to confirm this association. PMID:23457501

  6. Association between Insulin Resistance and Breast Carcinoma: A Systematic Review and Meta-Analysis

    PubMed Central

    Hernandez, Adrian V.; Guarnizo, Mirella; Miranda, Yony; Pasupuleti, Vinay; Deshpande, Abhishek; Paico, Socorro; Lenti, Hosten; Ganoza, Silvia; Montalvo, Laritza; Thota, Priyaleela; Lazaro, Herbert

    2014-01-01

    Objective This study was undertaken to evaluate the association between components defining insulin resistance and breast cancer in women. Study Design We conducted a systematic review of four databases (PubMed-Medline, EMBASE, Web of Science, and Scopus) for observational studies evaluating components defining insulin resistance in women with and without breast cancer. A meta-analysis of the association between insulin resistance components and breast cancer was performed using random effects models. Results Twenty-two studies (n = 33,405) were selected. Fasting insulin levels were not different between women with and without breast cancer (standardized mean difference, SMD −0.03, 95%CI −0.32 to 0.27; p = 0.9). Similarly, non-fasting/fasting C-peptide levels were not different between the two groups (mean difference, MD 0.07, −0.21 to 0.34; p = 0.6). Using individual odds ratios (ORs) adjusted at least for age, there was no higher risk of breast cancer when upper quartiles were compared with the lowest quartile (Q1) of fasting insulin levels (OR Q2 vs. Q1 0.96, 0.71 to 1.28; OR Q3 vs. Q1 1.22, 0.91 to 1.64; OR Q4 vs. Q1 0.98, 0.70 to 1.38). Likewise, there were no differences for quartiles of non-fasting/fasting C-peptide levels (OR Q2 vs. Q1 1.12, 0.91 to 1.37; OR Q3 vs. Q1 1.20, 0.91 to 1.59; OR Q4 vs. Q1 1.40, 1.03 to 1.92). Homeostatic model assessment (HOMA-IR) levels in breast cancer patients were significantly higher than in people without breast cancer (MD 0.22, 0.13 to 0.31, p<0.00001). Conclusions Higher levels of fasting insulin or non-fasting/fasting C-peptide are not associated with breast cancer in women. HOMA-IR levels are slightly higher in women with breast cancer. PMID:24911052

  7. Association between COX-2 rs2745557 polymorphism and prostate cancer risk: a systematic review and meta-analysis

    PubMed Central

    2012-01-01

    Background Evidence is accumulating that chronic inflammation may have an important role in prostate cancer (PCa). The COX-2 polymorphism rs2745557 (+202 C/T) has been extensively investigated as a potential risk factor for PCa, but the results have thus far been inconclusive. This meta-analysis was performed to derive a more precise estimation of the association. Methods A comprehensive search was conducted to identify all case-control studies of COX-2 rs2745557 polymorphism and PCa risk. We used odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) give a sense of the precision of the estimate. Statistical analyses were performed by Review Manage, version 5.0 and Stata 10.0. Results A total of 8 available studies were considered in the present meta-analysis, with 11356 patients and 11641 controls for rs2745557. When all groups were pooled, there was no evidence that rs2745557 had significant association with PCa under co-dominant, recessive, over-dominant, and allelic models. However, our analysis suggested that rs2745557 was associated with a lower PCa risk under dominant model in overall population (OR = 0.85, 95%CI = 0.74-0.97, P = 0.02). When stratifying for race, there was a significant association between rs2745557 polymorphism and lower PCa risk in dominant model comparison in the subgroup of Caucasians (OR = 0.86, 95%CI = 0.75-0.99, P = 0.04), but not in co-dominant, recessive, over-dominant and allelic comparisons. Conclusion Based on our meta-analysis, COX-2 rs2745557 was associated with a lower PCa risk under dominant model in Caucasians. PMID:22435969

  8. IFITM3 rs12252 T>C polymorphism is associated with the risk of severe influenza: a meta-analysis.

    PubMed

    Xuan, Y; Wang, L N; Li, W; Zi, H R; Guo, Y; Yan, W J; Chen, X B; Wei, P M

    2015-10-01

    The interferon-inducible transmembrane protein 3 (IFITM3), as one of the key genes involved in the interferon pathway, is critical for defending the host against influenza virus, and the rs12252 T>C variant in IFITM3 might be associated with susceptibility to severe influenza. Owing to contradictory and inconclusive results, we performed a meta-analysis to assess the association between rs12252 T>C polymorphism and severe influenza risk. A comprehensive literature search up to 1 August 2014 was conducted in EMBASE, Pubmed, Web of Science, VIP, Wanfang and CNKI databases. Four eligible studies with a total of 445 influenza patients and 3396 controls were included in this meta-analysis. Overall, our results demonstrated a significant association between the IFITM3 rs12252 T>C polymorphism and influenza risk [C vs. T: odds ratio (OR) 1·68, 95% confidence interval (CI) 1·32-2·13; CC vs. CT+TT: OR 2·38, 95% CI 1·52-3·73; CC+CT vs. TT: OR 1·62, 95% CI 1·18-2·22]. Stratification by ethnicity indicated that the variant C allele was associated with an 88% increased risk of influenza in Asians (C vs. T: OR 1·88, 95% CI 1·34-2·62). Moreover, subjects carrying the variant C allele had an increased risk of developing severe illness upon influenza infection (C vs. T: OR 2·70, 95% CI 1·86-3·94). However, no significant association was observed in patients with mild infection (C vs. T: OR 1·26, 95% CI 0·93-1·71). Our meta-analysis suggests that IFITM3 rs12252 T>C polymorphism is significantly associated with increased risk of severe influenza but not with the chance of initial virus infection. PMID:25778715

  9. Association of the methylenetetrahydrofolate reductase gene C677T polymorphism with the risk of male infertility: a meta-analysis.

    PubMed

    Zhu, Xudong; Liu, Zhiguo; Zhang, Maochen; Gong, Ruihong; Xu, Yajun; Wang, Baoming

    2016-03-01

    Several molecular epidemiological studies have been conducted to examine the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and male infertility susceptibility, but the results remain inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. In this meta-analysis, a total of 26 case-control studies including 5659 infertility cases and 5528 controls were selected to evaluate the possible association. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of association of C677T polymorphism with male infertility in the additive model, dominant model, recessive model and allele-frequency genetic model. In the overall analysis, the frequency of the 677T allele was significantly associated with male infertility susceptibility (OR = 2.32, 95%CI = 2.04-2.65 for TT vs. CC genotype; OR = 1.09, 95%CI = 1.00-1.19 for CT vs. CC genotype; OR = 1.19, 95%CI = 1.10-1.29 for CT/TT vs. CC genotype; OR = 1.54, 95%CI = 1.36-1.74 for TT vs. CC/TT genotype; OR = 1.22, 95%CI = 1.15-1.30 for T vs. C allele). A subgroup analysis of the subjects showed that significantly strong association between MTHFR C677T polymorphism and male infertility was present only in Asians, but not in Caucasians. Additionally, MTHFR C677T was associated with a significant increase in the risk of azoospermia in all genetic models. Meanwhile, no significantly increased risks of oligoasthenotertozoospermia (OAT) were found in most of the genetic models. In conclusion, this meta-analysis is in favor that the MTHFR C677T polymorphism is capable of causing male infertility susceptibility, especially in Asians and the subgroup of azoospermia. PMID:26584688

  10. Meta-Analysis of miR-146a Polymorphisms Association with Coronary Artery Diseases and Ischemic Stroke

    PubMed Central

    Bao, Mei-Hua; Xiao, Yan; Zhang, Qing-Song; Luo, Huai-Qing; Luo, Ji; Zhao, Juan; Li, Guang-Yi; Zeng, Jie; Li, Jian-Ming

    2015-01-01

    Coronary artery disease (CAD) and ischemic stroke (IS) are manifestations of atherosclerosis, with a high death rate. miR-146a is a microRNA that participates in the progress of CAD and IS. A single nucleotide polymorphism (SNP) in the precursor of miR-146a, rs2910164, was found to be associated with the risks of CAD and IS. However, the results were inconsistent and inconclusive. A meta-analysis was performed to assess the relationship of rs2910164 and CAD as well as IS susceptibility. The database Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM) were searched for related studies. Crude odds ratios with 95% confidence intervals were used to investigate the strength of the association by random- or fixed-effect model. A total of eight studies, with 3138 cases and 3097 controls were identified for the meta-analysis. The results shows that rs2910164 is associated with the risk of CAD significantly in allelic model (OR = 0.86), homozygous model (OR = 0.70), heterozygous model (OR = 0.80) and dominant model (OR = 0.76). The subjects carrying the GG genotype, GG + GC genotype or G allele are at lower risks of CAD. For the susceptibility of IS, there are no significant associations between rs2910164 and total studies. However, in subgroup analysis by sample size and ethnicity, the GG, GG + GC and G allele of rs2910164 are found to be associated with higher risks of IS in large sample size group and in Koreans, under homozygous and dominant models. In conclusion, the current meta-analysis suggests lower risks of CAD for GG, GG + GC genotype and G allele of rs2910164, while rs2910164 is not associated with the risk of IS. Thus rs2910164 might be recommended as a predictor for susceptibility of CAD, but not IS. PMID:26114385

  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. PMID:26681493

  12. Association Between Gene Polymorphisms on Chromosome 1 and Susceptibility to Pre-Eclampsia: An Updated Meta-Analysis.

    PubMed

    Zhang, Guixin; Zhao, Jinheng; Yi, Jianping; Luan, Yuanyuan; Wang, Qian

    2016-01-01

    BACKGROUND This meta-analysis enabled us to obtain a precise estimation of the association between gene polymorphisms on chromosome 1 (MTHFR, AGT, F5, IL-10, LEPR) and the susceptibility to pre-eclampsia (PE) in order to reach a uniform conclusion. MATERIAL AND METHODS Web of Science, PubMed, EMBASE, Cochran Library (CENTRAL), and Chinese databases (Chinese National Knowledge Infrastructure-CNKI and Wan Fang) were electronically searched to select relevant studies for this meta-analysis. We selected 95 case-control studies investigating 5 genes (MTHFR, AGT, F5, IL-10, and LEPR) with 8 SNPs. Odds ratios (OR) with their 95% confidence intervals (CI) were used for estimating the association. RESULTS A total of 16 646 PE patients and 28 901 normal-pregnancy patients were included in this meta-analysis. The overall results suggested that rs1801133 of MTHFR (OR=1.17, 95% CI: 1.05-1.13) and rs6025 of F5 (OR=1.53, 95%CI: 1.07-2.20) are significantly associated with PE, whereas rs1801131 of MTHFR, rs699 and rs4762 of AGT, rs1800896 and rs1800871 of IL-10, and rs1137101 of LEPR have no significant association with PE. Subgroup analysis by ethnicity revealed that, except for MTHFR rs1801133 and F5 rs6025 in Caucasians, which were significantly associated with an increased risk of PE, none of these SNPs were significantly associated with PE. As suggested by a symmetric funnel plot in conjunction with the Egger's test, there was no significant publication bias in MTHFR rs1801133 (P=0.318) and rs1801131 (P=0.204), F5 rs6025 (P=0.511), LEPR rs1137101 (P=0.511), AGT rs4762 (P=0.215) and rs699 (P=0.482), IL-10 rs1800871 (P=0.955), and rs1800896 (P=0.144). CONCLUSIONS This meta-analysis provides evidence that MTHFR rs1801133 and F5 rs6025 are associated with an increased risk of PE, especially in Caucasians. However, we do not have sufficient evidence to conclude there is a significant association between other gene polymorphisms and PE. PMID:27348238

  13. Association Between Gene Polymorphisms on Chromosome 1 and Susceptibility to Pre-Eclampsia: An Updated Meta-Analysis

    PubMed Central

    Zhang, Guixin; Zhao, Jinheng; Yi, Jianping; Luan, Yuanyuan; Wang, Qian

    2016-01-01

    Background This meta-analysis enabled us to obtain a precise estimation of the association between gene polymorphisms on chromosome 1 (MTHFR, AGT, F5, IL-10, LEPR) and the susceptibility to pre-eclampsia (PE) in order to reach a uniform conclusion. Material/Methods Web of Science, PubMed, EMBASE, Cochran Library (CENTRAL), and Chinese databases (Chinese National Knowledge Infrastructure-CNKI and Wan Fang) were electronically searched to select relevant studies for this meta-analysis. We selected 95 case-control studies investigating 5 genes (MTHFR, AGT, F5, IL-10, and LEPR) with 8 SNPs. Odds ratios (OR) with their 95% confidence intervals (CI) were used for estimating the association. Results A total of 16 646 PE patients and 28 901 normal-pregnancy patients were included in this meta-analysis. The overall results suggested that rs1801133 of MTHFR (OR=1.17, 95% CI: 1.05–1.13) and rs6025 of F5 (OR=1.53, 95%CI: 1.07–2.20) are significantly associated with PE, whereas rs1801131 of MTHFR, rs699 and rs4762 of AGT, rs1800896 and rs1800871 of IL-10, and rs1137101 of LEPR have no significant association with PE. Subgroup analysis by ethnicity revealed that, except for MTHFR rs1801133 and F5 rs6025 in Caucasians, which were significantly associated with an increased risk of PE, none of these SNPs were significantly associated with PE. As suggested by a symmetric funnel plot in conjunction with the Egger’s test, there was no significant publication bias in MTHFR rs1801133 (P=0.318) and rs1801131 (P=0.204), F5 rs6025 (P=0.511), LEPR rs1137101 (P=0.511), AGT rs4762 (P=0.215) and rs699 (P=0.482), IL-10 rs1800871 (P=0.955), and rs1800896 (P=0.144). Conclusions This meta-analysis provides evidence that MTHFR rs1801133 and F5 rs6025 are associated with an increased risk of PE, especially in Caucasians. However, we do not have sufficient evidence to conclude there is a significant association between other gene polymorphisms and PE. PMID:27348238

  14. Association between XRCC1 polymorphism 399 G->A and glioma among Caucasians: a systematic review and meta-analysis

    PubMed Central

    2012-01-01

    Background The x-ray cross complementing group 1 gene (XRCC1) is crucial to proper repair of DNA damage such as single-strand DNA breaks. A non-synonymous polymorphism in XRCC1, 399 G → A, has been shown to reduce effectiveness of such DNA repair and has been associated with the risk of certain cancers. The known risk for glioma from high dose ionizing radiation makes associations between this polymorphism and glioma of particular interest. Methods A systematic literature review and meta-analysis was conducted to explore the association between XRCC1 399 G → A and glioma. Subgroup analyses by grade, gender, genotyping method, country in which study was conducted, and study size were conducted when data were available and validity of the results were assessed by influence analyses and exploration of potential publication bias. Results Six studies were eligible for meta-analysis including data on 2,362 Caucasian glioma cases and 3,085 Caucasian controls. Pooled analysis yielded a significant association between the variant of interest and risk of glioma (OR = 1.17, 95% CI: 1.05-1.30) which was found to be disproportionately driven by a single study. Exclusion of this study, in an influence analysis, produced no statistically significant evidence of association with glioma (OR = 1.10, 95% CI: 0.98-1.23), and no evidence of publication bias. Conclusions This meta-analysis does not suggest a major role of the XRCC1 399 G → A polymorphism in influencing risk of glioma among Caucasians. Future studies should report data separately for glioma subtypes to permit stratified analyses for Grade III and Grade IV glioma and examine other polymorphisms in this gene. PMID:23101479

  15. Association between thrombin-activatable fibrinolysis inhibitor gene polymorphisms and venous thrombosis risk: a meta-analysis.

    PubMed

    Wang, Wei; Ma, He; Lu, Lili; Sun, Guixiang; Liu, Dang; Zhou, Yunti; Tong, Yue; Lu, Zhaojun

    2016-06-01

    Thrombin-activatable fibrinolysis inhibitor (TAFI) is an important antifibrinolytic factor that has been shown in increased concentrations to be associated with an increased risk for venous thrombosis. However, the effect of TAFI gene polymorphisms on the risk of venous thrombosis remains debatable. The aim of the current study was to evaluate the association of three single nucleotide polymorphisms: 505G>A (rs3742264), 1040 C>T (rs1926447) and -438G>A (rs2146881) with venous thrombosis risk using a meta-analysis. A systematic literature search for eligible studies published before 20 January 2015 was conducted in PubMed, EMBASE, Web of Science, WanFang database and Chinese National Knowledge Infrastructure. We assessed the possible association by pooled odds ratio and its 95% confidence interval. A total of 14 independent case-control studies including 2970 cases and 3049 controls were enrolled in the final meta-analysis. A significant reduction of venous thrombosis risk in the 505G>A polymorphism was observed under allele comparison, homozygote comparison and recessive models, but opposite results were seen in Asians. Likewise, there was a significant decreased susceptibility to venous thrombosis in the 1040C>T polymorphism in homozygote comparison and recessive models. In the subgroup analysis, the nonvenous thromboembolism disease group showed a significantly increased venous thrombosis risk. Pooled estimates did not show evidence of association between -438G>A and venous thrombosis risk in any genetic model. This meta-analysis suggested that although the -438G>T polymorphism is not correlated with venous thrombosis risk in all models, a trend toward reduced risk still could be observed. The A allele and AA genotype of 505G>A in whites and the TT genotype of 1040C>T were significantly associated with a decreased risk of venous thrombosis, except in the non-venous thromboembolism group. PMID:26656901

  16. Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case-control studies.

    PubMed

    Tizaoui, Kalthoum; Kaabachi, Wajih; Hamzaoui, Agnès; Hamzaoui, Kamel

    2015-03-01

    Vitamin D receptor (VDR) polymorphisms have been studied as potential contributors to multiple sclerosis (MS). However, published studies differ with respect to study design and the significance of the effects detected. The aim of this study was to quantify the magnitude of the risk associated with the TaqI, BsmI, ApaI and FokI VDR polymorphisms in MS using a meta-analysis approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic search and meta-analysis of the literature. Subgroup analyses were performed to detect potential sources of heterogeneity from the selected study characteristics. The stability of the summary risk was evaluated using sensitivity analyses. The meta-analysis included a total of 3300 cases and 3194 controls from 13 case-control studies. There were no significant associations found between TaqI and BsmI polymorphisms and MS risk. The association between the ApaI polymorphism and MS risk was significant in the homozygous and codominant models (P=0.013 and P=0.031, respectively), suggesting that the AA ApaI genotype might be a significant MS risk factor. Publication year and age significantly affected the association between TaqI polymorphisms and MS (P=0.014 and P=0.010, respectively), which indicates a protective effect of the major T allele. The AA ApaI and FF FokI genotypes are significant risk factors for MS. The association between the TaqI polymorphism and MS risk is significantly affected by study characteristics. PMID:24998351

  17. Genetic Associations of Interleukin-related Genes with Graves’ Ophthalmopathy: a Systematic Review and Meta-analysis

    PubMed Central

    Wong, Kah Hie; Rong, Shi Song; Chong, Kelvin K. L.; Young, Alvin L.; Pang, Chi Pui; Chen, Li Jia

    2015-01-01

    Graves’ ophthalmopathy (GO) is the commonest extra-thyroidal manifestation of Graves’ disease (GD). Associations between interleukin-related (IL) gene polymorphisms and GO have been reported in different populations. We aim to confirm such associations by conducting a meta-analysis. Totally 382 publications were retrieved in MEDLINE and EMBASE up to 25/2/2015. After removing the duplicates and assessing the studies, we retrieved 16 studies that met the selection criteria for meta-analysis, involving 12 polymorphisms in 8 IL-related genes, and 1650 GO cases and 2909 GD controls. The summary odds ratio (OR) and 95% confidence intervals (CI) were estimated. We found one polymorphism in IL1A (rs1800587, c.-889C>T) showing a suggestive association with GO in the meta-analysis (allelic model [T vs. C]: OR = 1.62, 95% CI: 1.00–2.62, P = 0.050, I2 = 53.7%; recessive model [TT vs. TC + CC]: OR = 2.39, 95% CI: 1.07–5.37, P = 0.039, I2 = 23.6%; heterozygous model [TC vs. CC]: OR = 1.52, 95% CI: 1.04–2.22, P = 0.034, I2 = 37.0%). No association with GO was detected for the other 7 genes (IL1B, IL1RA, IL4, IL6, IL12B, IL13 and IL23R). Our results thus indicate that IL1A is likely to be a genetic biomarker for GO. Further studies with larger sample sizes are warranted to confirm the associations of IL1A and other IL-related genes with GO. PMID:26578206

  18. Gene-based meta-analysis of genome-wide association studies implicates new loci involved in obesity.

    PubMed

    Hägg, Sara; Ganna, Andrea; Van Der Laan, Sander W; Esko, Tonu; Pers, Tune H; Locke, Adam E; Berndt, Sonja I; Justice, Anne E; Kahali, Bratati; Siemelink, Marten A; Pasterkamp, Gerard; Strachan, David P; Speliotes, Elizabeth K; North, Kari E; Loos, Ruth J F; Hirschhorn, Joel N; Pawitan, Yudi; Ingelsson, Erik

    2015-12-01

    To date, genome-wide association studies (GWASs) have identified >100 loci with single variants associated with body mass index (BMI). This approach may miss loci with high allelic heterogeneity; therefore, the aim of the present study was to use gene-based meta-analysis to identify regions with high allelic heterogeneity to discover additional obesity susceptibility loci. We included GWAS data from 123 865 individuals of European descent from 46 cohorts in Stage 1 and Metabochip data from additional 103 046 individuals from 43 cohorts in Stage 2, all within the Genetic Investigation of ANthropometric Traits (GIANT) consortium. Each cohort was tested for association between ∼2.4 million (Stage 1) or ∼200 000 (Stage 2) imputed or genotyped single variants and BMI, and summary statistics were subsequently meta-analyzed in 17 941 genes. We used the 'VErsatile Gene-based Association Study' (VEGAS) approach to assign variants to genes and to calculate gene-based P-values based on simulations. The VEGAS method was applied to each cohort separately before a gene-based meta-analysis was performed. In Stage 1, two known (FTO and TMEM18) and six novel (PEX2, MTFR2, SSFA2, IARS2, CEP295 and TXNDC12) loci were associated with BMI (P < 2.8 × 10(-6) for 17 941 gene tests). We confirmed all loci, and six of them were gene-wide significant in Stage 2 alone. We provide biological support for the loci by pathway, expression and methylation analyses. Our results indicate that gene-based meta-analysis of GWAS provides a useful strategy to find loci of interest that were not identified in standard single-marker analyses due to high allelic heterogeneity. PMID:26376864

  19. A Genome Wide Meta-Analysis Study for Identification of Common Variation Associated with Breast Cancer Prognosis

    PubMed Central

    Rafiq, Sajjad; Khan, Sofia; Tapper, William; Collins, Andrew; Upstill-Goddard, Rosanna; Gerty, Susan; Blomqvist, Carl; Aittomäki, Kristiina; Couch, Fergus J.; Liu, Jianjun

    2014-01-01

    Objective Genome wide association studies (GWAs) of breast cancer mortality have identified few potential associations. The concordance between these studies is unclear. In this study, we used a meta-analysis of two prognostic GWAs and a replication cohort to identify the strongest associations and to evaluate the loci suggested in previous studies. We attempt to identify those SNPs which could impact overall survival irrespective of the age of onset. Methods To facilitate the meta-analysis and to refine the association signals, SNPs were imputed using data from the 1000 genomes project. Cox-proportional hazard models were used to estimate hazard ratios (HR) in 536 patients from the POSH cohort (Prospective study of Outcomes in Sporadic versus Hereditary breast cancer) and 805 patients from the HEBCS cohort (Helsinki Breast Cancer Study). These hazard ratios were combined using a Mantel-Haenszel fixed effects meta-analysis and a p-value threshold of 5×10−8 was used to determine significance. Replication was performed in 1523 additional patients from the POSH study. Results Although no SNPs achieved genome wide significance, three SNPs have significant association in the replication cohort and combined p-values less than 5.6×10−6. These SNPs are; rs421379 which is 556 kb upstream of ARRDC3 (HR = 1.49, 95% confidence interval (CI) = 1.27–1.75, P = 1.1×10−6), rs12358475 which is between ECHDC3 and PROSER2 (HR = 0.75, CI = 0.67–0.85, P = 1.8×10−6), and rs1728400 which is between LINC00917 and FOXF1. Conclusions In a genome wide meta-analysis of two independent cohorts from UK and Finland, we identified potential associations at three distinct loci. Phenotypic heterogeneity and relatively small sample sizes may explain the lack of genome wide significant findings. However, the replication at three SNPs in the validation cohort shows promise for future studies in larger cohorts. We did not find strong evidence for concordance

  20. Genetic Association of CHAT rs3810950 and rs2177369 Polymorphisms with the Risk of Alzheimer's Disease: A Meta-Analysis

    PubMed Central

    Liu, Yong; Chen, Qicong; Liu, Xu; Dou, Mengmeng; Li, Silu; Zhou, Jiahui; Liu, Hong

    2016-01-01

    Choline acetyltransferase (CHAT) rs3810950 and rs2177369 polymorphisms have been implicated in susceptibility to Alzheimer's disease (AD). Due to the inconsistent results from previous studies, a meta-analysis was performed to estimate the association between these polymorphisms and AD risk more precisely. Pooled results of our meta-analysis indicated CHAT rs2177369 polymorphism was correlated with decreasing AD risk in one of five genetic models (dominant: OR = 0.77, 95% CI: 0.62–0.96), while rs3810950 mutant was associated with AD development in three models (allelic: OR = 1.18, 95% CI: 1.01–1.37, homozygous: OR = 1.63, 95% CI: 1.09–2.42, and recessive: OR = 1.65, 95% CI: 1.20–2.26). In subgroup analysis by ethnicity, the association between CHAT rs3810950 polymorphism and AD risk was just found in the recessive model (OR = 1.47, 95% CI: 1.05–2.07) among Caucasians, while four genetic models (allelic: OR = 1.23, 95% CI: 1.01–1.48; homozygous: OR = 2.24, 95% CI: 1.48–3.39; dominant: OR = 1.21, 95% CI: 1.06–1.40; and recessive: OR = 2.18, 95% CI: 1.45–3.29) assumed this association in Asians. In conclusion, our meta-analysis indicated CHAT rs2177369 polymorphism might play a protective role in AD, while rs3810950 variant was a risk factor for AD but its single heterozygous mutations might not influence susceptibility to AD. PMID:27597977

  1. Genetic Association of CHAT rs3810950 and rs2177369 Polymorphisms with the Risk of Alzheimer's Disease: A Meta-Analysis.

    PubMed

    Liu, Yong; Chen, Qicong; Liu, Xu; Dou, Mengmeng; Li, Silu; Zhou, Jiahui; Liu, Hong; Wu, Yongfu; Huang, Zunnan

    2016-01-01

    Choline acetyltransferase (CHAT) rs3810950 and rs2177369 polymorphisms have been implicated in susceptibility to Alzheimer's disease (AD). Due to the inconsistent results from previous studies, a meta-analysis was performed to estimate the association between these polymorphisms and AD risk more precisely. Pooled results of our meta-analysis indicated CHAT rs2177369 polymorphism was correlated with decreasing AD risk in one of five genetic models (dominant: OR = 0.77, 95% CI: 0.62-0.96), while rs3810950 mutant was associated with AD development in three models (allelic: OR = 1.18, 95% CI: 1.01-1.37, homozygous: OR = 1.63, 95% CI: 1.09-2.42, and recessive: OR = 1.65, 95% CI: 1.20-2.26). In subgroup analysis by ethnicity, the association between CHAT rs3810950 polymorphism and AD risk was just found in the recessive model (OR = 1.47, 95% CI: 1.05-2.07) among Caucasians, while four genetic models (allelic: OR = 1.23, 95% CI: 1.01-1.48; homozygous: OR = 2.24, 95% CI: 1.48-3.39; dominant: OR = 1.21, 95% CI: 1.06-1.40; and recessive: OR = 2.18, 95% CI: 1.45-3.29) assumed this association in Asians. In conclusion, our meta-analysis indicated CHAT rs2177369 polymorphism might play a protective role in AD, while rs3810950 variant was a risk factor for AD but its single heterozygous mutations might not influence susceptibility to AD. PMID:27597977

  2. Genetic association between interluekin-4 rs2243250 polymorphism and gastric cancer susceptibility: evidence based on a meta-analysis

    PubMed Central

    Zhang, Chi; Huang, Jing-Yu; He, Zi-Qi; Weng, Hong

    2016-01-01

    Purpose Numerous studies have suggested that the interleukin-4 (IL-4) rs2243250 polymorphism is associated with gastric cancer susceptibility. However, the results were inconsistent. Hence, we carried out a meta-analysis to confirm the conclusion. Methods We searched PubMed, Embase, CBM, CNKI, and Wanfang Data to identify relevant studies up to August 20, 2015. Odds ratio (OR) and 95% confidence interval (CI) were used to estimate the association between IL-4 rs2243250 polymorphism and gastric cancer susceptibility. All the statistical analyses were performed with Stata 12.0 software. Results A total of eleven published case–control studies were identified, including 2,247 gastric cancer patients and 3,370 controls. Overall, no significant association between IL-4 rs2243250 polymorphism and gastric cancer susceptibility was observed in this meta-analysis (T vs C: OR =1.05, 95% CI =0.95–1.17; TT vs CC: OR =1.20, 95% CI =0.89–1.63; CT vs CC: OR =1.14, 95% CI =0.87–1.48; TT + CT vs CC: OR =1.13, 95% CI =0.89–1.44; TT vs CT + CC: OR =1.02, 95% CI =0.88–1.20). Similar results were found in subgroup analyses according to ethnicity and Hardy–Weinberg equilibrium in controls. Conclusion This meta-analysis suggests that IL-4 rs2243250 polymorphism may not be associated with gastric cancer susceptibility. Further studies are needed to validate this conclusion. PMID:27143935

  3. Staphylococcus aureus superantigens are associated with chronic rhinosinusitis with nasal polyps: a meta-analysis.

    PubMed

    Ou, Jing; Wang, Jun; Xu, Yu; Tao, Ze-zhang; Kong, Yong-gang; Chen, Shi-ming; Shi, Wen-dan

    2014-10-01

    Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common health problem in the world. However, its etiology remains unclear. Recent researches have hypothesized that Staphylococcus aureus (SA) exotoxins which act as superantigens might be associated with inflammatory mucosal changes seen in CRSwNP. The objective of this study is to evaluate the relationship between Staphylococcus aureus superantigens and CRSwNP. PubMed, MEDLINE, EMBASE, Cochrane Library and CNKI were searched to collect the case-control studies on the relationship between SA superantigens and CRSwNP from the date of establishment of the databases to May 2013. The extracted data were analyzed by RevMan 5.0. The main outcome measures were SA culture-positive rate, the detection rate of SA superantigens and its specific IgE. Twelve studies including 340 cases and 178 controls were selected. The results showed that SA culture-positive rate in the CRSwNP group was significantly higher than that in the control group (OR 4.85, 95% CI 1.80-13.05, P = 0.002), the detection rate of SA superantigens and its specific IgE in the CRSwNP group were both significantly higher than that in the control group (OR 12.07, 95% CI 4.57-31.90, P < 0.00001; OR 17.03, 95% CI 5.43-53.39, P < 0.00001, respectively) and the CD4(+) T cell counts and Lund-Mackay CT scores were statistically higher in the IgE-positive group than in the IgE-negative group (MD 16.26, 95% CI 4.86-27.67, P = 0.005, MD 2.43, 95 % CI 0.39-4.48, P = 0.02, respectively). However, the eosinophil and CD8(+) T cell counts showed no difference between IgE-positive group and -negative group. This meta-analysis indicated that the SA superantigens may be a risk factor for CRSwNP, and the presence of SA superantigen is related to the disease severity of CRSwNP. PMID:24604680

  4. The association of glutathione S-transferase polymorphisms in patients with osteosarcoma: evidence from a meta-analysis.

    PubMed

    Wang, Z; Xu, H; He, M; Wu, H; Zhu, Y; Su, Z

    2015-05-01

    Osteosarcoma is a life-threatening malignancy that often occurs in teenagers. Numerous studies have reported glutathione S-transferase polymorphisms are associated with osteosarcoma, but the results are inconclusive, partially because the sample size in each of published studies is relatively small. Therefore, we performed a meta-analysis of the published studies to estimate the association more accurately. To preciously examine the association between the glutathione S-transferase polymorphisms and osteosarcoma, we undertook a meta-analysis of six case-control studies. The association between the glutathione S-transferase polymorphisms and osteosarcoma risk was assessed by odds ratios together with their 95% confidence intervals using a fixed-effects model or random-effects model. In addition, hazard ratio was used to measure the relationship between glutathione S-transferase polymorphisms and prognosis in patients with osteosarcoma. We found that there was significant association between the polymorphisms in GSTT1 or GSTM3 (AA versus BB) and osteosarcoma risk. In addition, there is no evidence of association on GSTM1, GSTT1, GSTP1 (IIe/IIe versus IIe/Val) or GSTP1 (IIe/IIe versus Val/Val) polymorphisms with prognosis in osteosarcoma. In conclusion, the GSTT1 and GSTM3 polymorphisms might influence osteosarcoma risk. PMID:24689813

  5. 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

  6. The Association between HMGA1 rs146052672 Variant and Type 2 Diabetes: A Transethnic Meta-Analysis

    PubMed Central

    Nobile, Carmelo G. A.; Foti, Daniela; Pavia, Maria; Brunetti, Antonio

    2015-01-01

    The high-mobility group A1 (HMGA1) gene has been previously identified as a potential novel candidate gene for susceptibility to insulin resistance and type 2 diabetes (T2D) mellitus. For this reason, several studies have been conducted in recent years examining the association of the HMGA1 gene variant rs146052672 (also designated IVS5-13insC) with T2D. Because of non-univocal data and non-overlapping results among laboratories, we conducted the current meta-analysis with the aim to yield a more precise and reliable conclusion for this association. Using predetermined inclusion criteria, MEDLINE, PubMed, Web of Science, Scopus, Google Scholar and Embase were searched for all relevant available literature published until November 2014. Two of the authors independently evaluated the quality of the included studies and extracted the data. Values from the single studies were combined to determine the meta-analysis pooled estimates. Heterogeneity and publication bias were also examined. Among the articles reviewed, five studies (for a total of 13,789 cases and 13,460 controls) met the predetermined criteria for inclusion in this meta-analysis. The combined adjusted odds ratio estimates revealed that the rs146052672 variant genotype had an overall statistically significant effect on increasing the risk of development of T2D. As most of the study subjects were Caucasian, further studies are needed to establish whether the association of this variant with an increased risk of T2D is generalizable to other populations. Also, in the light of this result, it would appear to be highly desirable that further in-depth investigations should be undertaken to elucidate the biological significance of the HMGA1 rs146052672 variant. PMID:26296198

  7. TLR1, 2, 4, 6 and 9 Variants Associated with Tuberculosis Susceptibility: A Systematic Review and Meta-Analysis

    PubMed Central

    Schurz, Haiko; Daya, Michelle; Möller, Marlo; Hoal, Eileen G.; Salie, Muneeb

    2015-01-01

    Background Studies investigating the influence of toll-like receptor (TLR) polymorphisms and tuberculosis susceptibility have yielded varying and often contradictory results in different ethnic groups. A meta-analysis was conducted to investigate the relationship between TLR variants and susceptibility to tuberculosis, both across and within specific ethnic groups. Methods An extensive database search was performed for studies investigating the relationship between TLR and tuberculosis (TB) susceptibility. Data was subsequently extracted from included studies and statistically analysed. Results 32 articles involving 18907 individuals were included in this meta-analysis, and data was extracted for 14 TLR polymorphisms. Various genetic models were employed. An increased risk of TB was found for individuals with the TLR2 rs3804100 CC and the TLR9 rs352139 GA and GG genotypes, while decreased risk was identified for those with the AG genotype of TLR1 rs4833095. The T allele of TLR6 rs5743810 conferred protection across all ethnic groups. TLR2 rs5743708 subgroup analysis identified the A allele to increase susceptibility to TB in the Asian ethnic group, while conferring protection in the Hispanic group. The T allele of TLR4 rs4986791 was also found to increase the risk of TB in the Asian subgroup. All other TLR gene variants investigated were not found to be associated with TB in this meta-analysis. Discussion Although general associations were identified, most TLR variants showed no significant association with TB, indicating that additional studies investigating a wider range of pattern recognition receptors is required to gain a better understanding of this complex disease. PMID:26430737

  8. Association between Footwear Use and Neglected Tropical Diseases: A Systematic Review and Meta-Analysis

    PubMed Central

    Brooker, Simon J.; Clark, Hannah; Rafique, Khizar; Knopp, Stefanie; Utzinger, Jürg; Davey, Gail

    2014-01-01

    Background The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs. Methodology We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses. Principal Findings Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR = 0.15; 95% CI: 0.08–0.29), CLM (OR = 0.24; 95% CI: 0.06–0.96), tungiasis (OR = 0

  9. Association between β1 adrenergic receptor gene Arg389Gly polymorphism and risk of heart failure: a meta-analysis.

    PubMed

    Ma, S T; Zhao, W; Liu, B; Jia, R Y; Zhao, C J; Cui, L Q

    2015-01-01

    Numerous studies have evaluated the association between Arg389Gly polymorphism in the β1 adrenergic receptor gene and heart failure risk. However, the specific association is still controversial. We performed a meta-analysis of all case-control studies that evaluated the association between Arg389Gly polymorphism and heart failure in humans. Studies were identified in the PubMed, Embase, and China National Knowledge Infrastructure databases. Two reviewers independently assessed the studies. Six case-control studies with a total of 1736 participants were included in the meta-analysis, including 882 cases with heart failure and 854 controls, and our results showed no association between the Arg389Gly polymorphism and heart failure [ArgArg vs GlyGly: odds ratio (OR) = 0.84, 95% confidence interval (CI) 0.59-1.20; ArgArg vs ArgGly: OR = 0.95, 95%CI 0.78-1.16; dominant model: OR = 1.08, 95%CI 0.89-1.31; recessive model: OR = 0.96, 95%CI 0.69-1.35]. No publication bias was found in the present study (all P values > 0.05). In conclusion, the β1 adrenergic receptor gene Arg389Gly polymorphism might not be associated with heart failure risk. Further large and well-designed studies are needed to confirm this conclusion. PMID:26125791

  10. Association of COX-2 -765G>C genetic polymorphism with coronary artery disease: a meta-analysis

    PubMed Central

    Zhang, Ming-Ming; Xie, Xiang; Ma, Yi-Tong; Zheng, Ying-Ying; Yang, Yi-Ning; Li, Xiao-Mei; Fu, Zhen-Yan; Liu, Fen; Chen, Bang-Dang

    2015-01-01

    Background: Previous studies suggested the single nucleotide polymorphism (SNP) of COX-2 -765G>C (rs20417) is associated with coronary artery disease (CAD), but the results were conflicting. In order to derive a more precise estimation of the associations, we performed a meta-analysis of the relationship between rs20417 and CAD in all published studies. Method: Databases including PubMed, Web of Science, Wanfang, SinoMed and CNKI were systematically searched. Data were extracted using standardized methods. The association was assessed by odds ratio (OR) with 95% confidence intervals (CIs).The statistical tests were performed using Review Manager 5.3.3 and Stata 12.0 software. Results: We identified a total of 14 studies involving a total of 18227 subjects. The pooled odds ratio (OR) for the association between COX-2 -765G>C and CAD and its corresponding 95% confidence interval (95% CI) were evaluated by random or fixed effect model. A significant statistical association between COX-2 -765G>C and CAD was observed in an allelic model (P=0.02, OR=0.64, 95% CI: 0.43-0.94), dominant model (P=0.04, OR=0.74, 95% CI: 0.56-0.99), and recessive model (P=0.02, OR=0.46, 95% CI: 0.23-0.90). Conclusion: This meta-analysis suggested that COX-2 -765G>C is a protective for CAD. PMID:26221283

  11. Association between DRD2/ANKK1 TaqIA Polymorphism and Susceptibility with Tourette Syndrome: A Meta-Analysis

    PubMed Central

    Yuan, Aihua; Su, Liang; Yu, Shunying; Li, Chunbo; Yu, Tao; Sun, Jinhua

    2015-01-01

    Background Genetic factors are important in the pathogenesis of Tourette syndrome (TS). Notably, Dopamine receptor D2 (DRD2) gene has been suggested as a possible candidate gene for this disorder. Several studies have demonstrated that DRD2/ANKK1 TaqIA polymorphism is associated with an increased risk of developing TS. However, past results remain conflicting. We addressed this controversy by performing a meta-analysis of the relationship between DRD2/ANKK1 TaqIA polymorphism and TS. Methods Literature was searched in multiple databases including PUBMED, COCHRANE and WEB OF SCIENCE up to July 2014. The number of the genotypes for DRD2/ANKK1 TaqIA in the TS and control subjects was extracted and statistical analysis was performed using Review Manager 5.0.16 and Stata 12.0 software. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) were utilized to calculate the risk of TS with DRD2/ANKK1 TaqIA. Stratified analysis based on ethnicity was also conducted. Results 523 patients with TS, 564 controls and 87 probands plus 152 relatives from five published studies were finally involved in this meta-analysis. Combined analysis revealed that the overall ORs for the DRD2/ANKK1 TaqIA A1 allele were 1.69 (95%CIs = 1.42-2.00) in the fixed-effect model and 1.66 (95%CIs = 1.33-2.08) in the random-effects model. Stratification by ethnicity indicated the TaqIA A1 allele was significantly associated with TS in Caucasians (fixed-effect model: OR=1.75, 95%CI = 1.43-2.16; random-effect model: OR=1.69, 95%CI = 1.25-2.28) and in Asians (OR=1.54, 95%CI = 1.12-2.10). Meta-analysis of the A1A1 vs. A2A2 (homozygous model), A1A2 vs. A2A2 (heterozygous model) and A1A1+A1A2 vs. A2A2 (dominant model) of this polymorphism revealed a significant association with TS in overall populations and Caucasians. Conclusions This meta-analysis suggested that the DRD2/ANKK1 TaqIA polymorphism might contribute to TS susceptibility, especially in Caucasian population. However, further investigation

  12. Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology.

    PubMed

    Springelkamp, Henriët; Mishra, Aniket; Hysi, Pirro G; Gharahkhani, Puya; Höhn, René; Khor, Chiea-Chuen; Cooke Bailey, Jessica N; Luo, Xiaoyan; Ramdas, Wishal D; Vithana, Eranga; Koh, Victor; Yazar, Seyhan; Xu, Liang; Forward, Hannah; Kearns, Lisa S; Amin, Najaf; Iglesias, Adriana I; Sim, Kar-Seng; van Leeuwen, Elisabeth M; Demirkan, Ayse; van der Lee, Sven; Loon, Seng-Chee; Rivadeneira, Fernando; Nag, Abhishek; Sanfilippo, Paul G; Schillert, Arne; de Jong, Paulus T V M; Oostra, Ben A; Uitterlinden, André G; Hofman, Albert; Zhou, Tiger; Burdon, Kathryn P; Spector, Timothy D; Lackner, Karl J; Saw, Seang-Mei; Vingerling, Johannes R; Teo, Yik-Ying; Pasquale, Louis R; Wolfs, Roger C W; Lemij, Hans G; Tai, E-Shyong; Jonas, Jost B; Cheng, Ching-Yu; Aung, Tin; Jansonius, Nomdo M; Klaver, Caroline C W; Craig, Jamie E; Young, Terri L; Haines, Jonathan L; MacGregor, Stuart; Mackey, David A; Pfeiffer, Norbert; Wong, Tien-Yin; Wiggs, Janey L; Hewitt, Alex W; van Duijn, Cornelia M; Hammond, Christopher J

    2015-03-01

    Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma. PMID:25631615

  13. Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology

    PubMed Central

    Springelkamp, Henriët; Mishra, Aniket; Hysi, Pirro G.; Gharahkhani, Puya; Höhn, René; Khor, Chiea-Chuen; Cooke Bailey, Jessica N.; Luo, Xiaoyan; Ramdas, Wishal D.; Vithana, Eranga; Koh, Victor; Yazar, Seyhan; Xu, Liang; Forward, Hannah; Kearns, Lisa S.; Amin, Najaf; Iglesias, Adriana I.; Sim, Kar-Seng; van Leeuwen, Elisabeth M.; Demirkan, Ayse; van der Lee, Sven; Loon, Seng-Chee; Rivadeneira, Fernando; Nag, Abhishek; Sanfilippo, Paul G.; Schillert, Arne; de Jong, Paulus T. V. M.; Oostra, Ben A.; Uitterlinden, André G.; Hofman, Albert; Zhou, Tiger; Burdon, Kathryn P.; Spector, Timothy D.; Lackner, Karl J.; Saw, Seang-Mei; Vingerling, Johannes R.; Teo, Yik-Ying; Pasquale, Louis R.; Wolfs, Roger C. W.; Lemij, Hans G.; Tai, E-Shyong; Jonas, Jost B.; Cheng, Ching-Yu; Aung, Tin; Jansonius, Nomdo M.; Klaver, Caroline C. W.; Craig, Jamie E.; Young, Terri L.; Haines, Jonathan L.; MacGregor, Stuart; Mackey, David A.; Pfeiffer, Norbert; Wong, Tien-Yin; Wiggs, Janey L.; Hewitt, Alex W.; van Duijn, Cornelia M.; Hammond, Christopher J.

    2015-01-01

    Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma. PMID:25631615

  14. A meta-analysis of the association between NQO1 C609T variation and acute myeloid leukemia risk.

    PubMed

    Li, Cuiping; Liu, Yun; Wei, Shujiao; Zhou, Yang

    2014-05-01

    Quinone oxidoreductase (NQO1) C609T polymorphisms have been implicated in acute myeloblastic leukemia (AML) risk, but previously published studies are inconsistent and recent meta-analyses have not been adequate. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. The quality of studies was evaluated by using the Newcastle-Ottawa Scale (NOS). Crude ORs with 95% CIs were used to assess the strength of association between the NQO1 C609T polymorphisms and AML risk. A total of 14 studies including 2,245 cases and 3,310 controls were involved in this meta-analysis. Overall, significantly elevated AML risk was associated with NQO1 C609T variant genotypes when all studies were pooled into the meta-analysis (TT vs. CC: OR = 1.44, 95% CI = 1.15-1.81; dominant model: OR = 1.35, 95% CI = 1.09-1.68). In the subgroup analysis by ethnicity, significantly increased risks were found for Asians (OR = 1.47, 95% CI = 1.13-1.93, P = 0.005, I(2) = 48.4%, P = 0.071 for heterogeneity). When stratified by studies of adults or children, statistically significantly elevated risks were found among adults (OR = 1.37, 95% CI = 1.06-1.76, P = 0.017, I(2) = 42.2%, P = 0.097 for heterogeneity). The accumulated evidence indicates that NQO1 C609T seems to confer a risk factor for AML among Asians and adults. Significant between-study heterogeneity was observed, thus more studies based on larger case-control population are required to further evaluate the role of NQO1 C609T polymorphism in AML. PMID:24474393

  15. Association between serum interleukin-6 concentrations and chronic obstructive pulmonary disease: a systematic review and meta-analysis

    PubMed Central

    Lin, Yi-hua

    2015-01-01

    Background. Interleukin-6 (IL-6) is an important pro-inflammatory cytokine and has been implicated to play a role in the systemic inflammation of patients with chronic obstructive pulmonary disease (COPD). We conducted this meta-analysis to assess the association between serum IL-6 concentrations and COPD. Methods. PubMed and Embase were searched for eligible studies. Data were extracted by two investigators (Wei J, Xiong XF) independently and analyzed using Review Manager 5.3 and STATA 12.0 software. Standard mean differences (SMDs) and 95% confidence intervals (CI) were calculated. Results. Thirty-three studies were included in this meta-analysis. The serum IL-6 concentrations were higher in patients with stable COPD than healthy controls (SMD = 0.65, 95% CI [0.51–0.79]). COPD patients without major comorbidities also showed higher IL-6 levels than healthy controls (SMD = 0.74, 95% CI [0.56–0.91]). COPD patients with an forced expiratory volume in one second (FEV1) of either <50% predicted or >50% predicted had increased IL-6 concentrations compared to healthy controls (SMD = 0.77, 95% CI [0.48–1.05], SMD = 1.01, 95% CI [0.43–1.59], respectively). The serum IL-6 concentrations between mild-moderate and severe-very severe COPD patient groups were not found to be significant (SMD = −0.1, 95% CI [−0.65–0.44]). Conclusions. This meta-analysis indicated that patients with stable COPD had higher serum IL-6 concentrations than healthy controls. No evidence showing positive or negative association between IL-6 concentrations and the severity of pulmonary function impairment was found. The correlation between IL-6 levels and pulmonary function was weak in different severities of stable COPD patients. PMID:26336642

  16. Evaluation of association of maternal IL-10 polymorphisms with risk of preeclampsia by A meta-analysis

    PubMed Central

    Yang, Wenchao; Zhu, Zhenmin; Wang, Jin; Ye, Wei; Ding, Yong

    2014-01-01

    Emerging evidence shows that interleukin (IL)-10 gene polymorphisms can regulate its expression level and thus influence person's susceptibility to preeclampsia. However, various published results were inconsistent. To explore the association between maternal IL-10 gene polymorphisms and preeclampsia, we performed a meta-analysis based upon 11 individual studies here. Our meta-analysis results indicated that IL-10 -819C/T (C versus T, OR = 1.28, 95% CI = 1.08–1.50, P = 0.003) and -592C/A (C versus A, OR = 1.28, 95% CI = 1.03–1.59, P = 0.03) polymorphisms were associated with preeclampsia. Although there was no overall association between -1082A/G polymorphism and preeclampsia (G versus A, OR = 0.93, 95% CI = 0.77–1.13, P = 0.49), such association existed among Asian (G versus A, OR = 1.29, 95% CI = 1.04–1.60, P = 0.02) and South American (G versus A, OR = 0.72, 95% CI = 0.54–0.94, P = 0.02) populations in the subgroup analysis stratified by continents. PMID:25257050

  17. Association between CEBPE Variant and Childhood Acute Leukemia Risk: Evidence from a Meta-Analysis of 22 Studies

    PubMed Central

    Tang, Linjun; Healy, Jasmine; Sinnett, Daniel; Dai, Yue-e

    2015-01-01

    The CCAAT/enhancer binding proteins (CEBPs) have been involved in the etiology of acute leukemia (AL) and investigated in numerous genetic association studies, however, the results were inconclusive. The current meta-analysis was conducted to clarify the effect of CEBPE rs2239633 variant on childhood AL risk. Electronic literature search was performed on August 15, 2014, from databases of Medline, PubMed, Embase, and Web of Science. A total of 22 case-control studies were eligible for the pooled analysis. The results demonstrated that rs2239633 A allele was significantly associated with a decreased risk of childhood AL (A vs G: OR=0.87, 95%CI = 0.80, 0.94, p<0.001), especially in B-cell ALL subgroup (A vs G: OR = 0.79, 95%CI = 0.74, 0.83, p<0.001), but not among T-cell ALL or AML subgroups. In the stratified analysis by ethnicity, the association was observed in Europeans (A vs G: OR = 0.80, 95%CI = 0.76, 0.84, p<0.001) but not in Asian and mixed populations. Moreover, the results of sensitivity and cumulative meta-analysis indicated the robustness of our results. Also, Begg’s and Egger’s tests did not indicate any evidence of obvious asymmetry. In summary, our study provided evidence that CEBPE rs2239633 variant is associated with decreased risk of childhood B-cell ALL in Europeans. PMID:25938438

  18. Association between alpha-1 antichymotrypsin gene A/T polymorphism and primary intracerebral hemorrhage: a meta-analysis.

    PubMed

    Ye, Zusen; Ye, Qiang; Shao, Bei; He, Jincai; Zhu, Zhenguo; Cheng, Jianhua; Chen, Yanyan; Chen, Siyan; Huang, Xiaoya

    2015-01-01

    The present study is to use meta-analysis to explain the association between alpha-1 antichymotrypsin (ACT) gene A/T polymorphism and the risk of primary intracerebral hemorrhage (PICH). Relevant studies before 1 June 2015 were identified by searching PubMed, Cochrane database and Science Citation Index Expanded (SCIE), and the references of retrieved articles. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were used to assess the strength of the association. Five independent publications, with 774 PICH cases and 940 controls, were included. There was no statistical evidence of association between ACT polymorphism and PICH risk under all genetic models in overall estimates (allele model: OR = 1.01, 95% CI = 0.80-1.28; heterozygote model: OR = 0.93, 95% CI = 0.60-1.45; homozygote model: OR = 1.03, 95% CI = 0.59-1.80; dominant model: OR = 0.97, 95% CI = 0.65-1.46; recessive model: OR = 1.06, 95% CI = 0.72-1.57). No association was found in subgroup analysis based on ethnicity, Hardy-Weinberg equilibrium, location of hematoma and blood pressure. Sensitivity analysis suggested that the combined results were stable and reliable. No significant publication bias was found by Begg's test and Egger's regression test. The results of our meta-analysis indicate that ACT polymorphism is unlikely to contribute to PICH susceptibility. PMID:26885003

  19. Association between alpha-1 antichymotrypsin gene A/T polymorphism and primary intracerebral hemorrhage: a meta-analysis

    PubMed Central

    Ye, Zusen; Ye, Qiang; Shao, Bei; He, Jincai; Zhu, Zhenguo; Cheng, Jianhua; Chen, Yanyan; Chen, Siyan; Huang, Xiaoya

    2015-01-01

    The present study is to use meta-analysis to explain the association between alpha-1 antichymotrypsin (ACT) gene A/T polymorphism and the risk of primary intracerebral hemorrhage (PICH). Relevant studies before 1 June 2015 were identified by searching PubMed, Cochrane database and Science Citation Index Expanded (SCIE), and the references of retrieved articles. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were used to assess the strength of the association. Five independent publications, with 774 PICH cases and 940 controls, were included. There was no statistical evidence of association between ACT polymorphism and PICH risk under all genetic models in overall estimates (allele model: OR = 1.01, 95% CI = 0.80-1.28; heterozygote model: OR = 0.93, 95% CI = 0.60-1.45; homozygote model: OR = 1.03, 95% CI = 0.59-1.80; dominant model: OR = 0.97, 95% CI = 0.65-1.46; recessive model: OR = 1.06, 95% CI = 0.72-1.57). No association was found in subgroup analysis based on ethnicity, Hardy-Weinberg equilibrium, location of hematoma and blood pressure. Sensitivity analysis suggested that the combined results were stable and reliable. No significant publication bias was found by Begg’s test and Egger’s regression test. The results of our meta-analysis indicate that ACT polymorphism is unlikely to contribute to PICH susceptibility. PMID:26885003

  20. The Association Between p53 Codon 72 Polymorphism and Endometrial Cancer Risk: A System Review and Meta-analysis.

    PubMed

    Yi, Ke; Yang, LingYun; Lan, Zhu; Xi, MingRong

    2016-07-01

    Polymorphism of p53 codon 72 plays an important role in pathogenesis and development of cancer. Published data on the association between the p53 codon 72 polymorphism and endometrial cancer risk are controversial. A meta-analysis was performed to assess whether the polymorphism of p53 codon 72 is associated with endometrial cancer risk. Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases were searched to identify eligible studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for p53 codon 72 polymorphism and endometrial cancer were appropriately derived from fixed-effects or random effects models. A total of 12 studies were enrolled in this meta-analysis. The pooled analyses revealed that p53 codon 72 polymorphism was not associated with endometrial cancer risk. Stratified analysis by Hardy-Weinberg equilibrium exhibited a significantly increased risk of endometrial cancer among studies deviated from Hardy-Weinberg equilibrium in heterozygote comparison (Pro/Arg vs Arg/Arg; OR, 0.61; 95% CI, 0.42-0.87) and dominant model (Pro/Pro + Pro/Arg vs Arg/Arg; OR, 0.66; 95% CI, 0.47-0.92). This study indicated that the p53 codon 72 polymorphism may not be associated with endometrial cancer risk. PMID:27327151

  1. Association of Plasma Transforming Growth Factor-β1 Levels and the Risk of Atrial Fibrillation: A Meta-Analysis

    PubMed Central

    Li, Jiao; Yang, Yajuan; Ng, Chee Yuan; Zhang, Zhiwei; Liu, Tong; Li, Guangping

    2016-01-01

    Introduction Numerous studies have demonstrated that plasma transforming growth factor-β1 (TGF-β1) may be involved in the pathogenesis of atrial fibrillation (AF), but some discrepancy remained. We performed a meta-analysis to evaluate the association between the plasma level of TGF-β1 and the risk of AF. Methods Published clinical studies evaluating the association between the plasma level of TGF-β1 and the risk of AF were retrieved from PubMed and EMBASE databases. Two reviewers independently evaluated the quality of the included studies and extracted study data. Subgroup analysis and sensitivity analysis were performed to evaluate for heterogeneity between studies. Results Of the 395 studies identified initially, 13 studies were included into our analysis, with a total of 3354 patients. Higher plasma level of TGF-β1 was associated with increased risk of AF when evaluated as both a continuous variable (SMD 0.67; 95%CI 0.29–1.05) and a categorical variable (OR 1.01, 95% CI 1.01–1.02). Conclusions This meta-analysis suggests an association between elevated plasma TGF-β1 and new onset AF. Additional studies with larger sample sizes are needed to further investigate the relationship between plasma TGF-β1 and the occurrence of AF. PMID:27171383

  2. Association between coffee consumption and the risk of oral cancer: a meta-analysis of observational studies

    PubMed Central

    Zhang, Ying; Wang, Xi; Cui, Dan

    2015-01-01

    Objective: Quantification of the association between the coffee consumption and risk of oral cancer is still conflicting. Thus, we conducted a meta-analysis to summarize the evidence from epidemiological studies of coffee consumption with the risk of oral cancer. Methods: Pertinent studies were identified by a search of PubMed and Web of Knowledge to March 2015. The random effect model was used. Sensitivity analysis and publication bias were conducted. Results: Data from 12 studies including 4,037 oral cancer cases and 1,872,231 participants were used in this meta-analysis. Pooled results suggested that highest coffee consumption amount versus lowest amount was significantly associated with the risk of oral cancer [summary relative risk (RR) = 0.694, 95% CI = 0.543-0.886, I2 = 65.0%]. The association was also significant in Europe [summary RR = 0.571, 95% CI = 0.378-0.863], but not in America. No publication bias was found. Conclusions: Our analysis suggested that the higher coffee consumption might reduce the risk of oral cancer, especially in Europe. PMID:26380002

  3. Association between sodium intakes with the risk of chronic kidney disease: evidence from a meta-analysis

    PubMed Central

    Liu, Nian; Sun, Weixia; Xing, Zhiwen; Ma, Fuzhe; Sun, Tao; Wu, Hao; Dong, Yijun; Xu, Zhonggao; Fu, Yaowen; Yuan, Hang

    2015-01-01

    Objective: Inconsistent results regarding the association between sodium intake and the risk of chronic kidney disease (CKD) have been reported. Thus, we conducted a meta-analysis to summarize the evidence from epidemiological studies of sodium with the risk of CKD. Methods: Pertinent studies were identified by searching of PubMed and Web of Science. The random effect model was used to combine the results. Meta-regression and subgroups analyses were used to explore potential sources of between-study heterogeneity. Publication bias was estimated using Egger’s regression asymmetry test. Results: Finally, 9 articles involving 5638 CKD cases were included in this meta-analysis. Pooled results suggested that highest sodium intake level versus lowest level was significantly associated with the risk of CKD [summary relative risk (RR) = 1.088, 95% CI = 1.009-1.193, I2 = 78.1%], especially among Europe [summary RR = 1.097, 95% CI = 1.009-1.205], but not in the America. The association was also found in the prospective studies [summary RR = 1.096, 95% CI = 1.007-1.192], but not in the cross-sectional studies. No evidence of significant publication bias was found. Conclusions: Higher sodium intake might increase the risk of CKD. PMID:26885022

  4. 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

    2012-08-01

    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. PMID:22797727

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

    PubMed Central

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

    2016-01-01

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

  6. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.

    PubMed

    Barrett, Jeffrey C; Clayton, David G; Concannon, Patrick; Akolkar, Beena; Cooper, Jason D; Erlich, Henry A; Julier, Cécile; Morahan, Grant; Nerup, Jørn; Nierras, Concepcion; Plagnol, Vincent; Pociot, Flemming; Schuilenburg, Helen; Smyth, Deborah J; Stevens, Helen; Todd, John A; Walker, Neil M; Rich, Stephen S

    2009-06-01

    Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7,514 cases and 9,045 reference samples. Forty-one distinct genomic locations provided evidence for association with T1D in the meta-analysis (P < 10(-6)). After excluding previously reported associations, we further tested 27 regions in an independent set of 4,267 cases, 4,463 controls and 2,319 affected sib-pair (ASP) families. Of these, 18 regions were replicated (P < 0.01; overall P < 5 × 10(-8)) and 4 additional regions provided nominal evidence of replication (P < 0.05). The many new candidate genes suggested by these results include IL10, IL19, IL20, GLIS3, CD69 and IL27. PMID:19430480

  7. Association of type 2 diabetes mellitus and the risk of colorectal cancer: A meta-analysis and systematic review

    PubMed Central

    Guraya, Salman Yousuf

    2015-01-01

    AIM: To provide a quantitative assessment of the association between type 2 diabetes mellitus (T2DM) and the risk of colorectal cancer (CRC). METHODS: Systematic review was conducted thorough MEDLINE, EMBASE, Cochrane Library, and ISI Web of knowledge databases till 31st January 2014. This meta-analysis included the cohort studies that illustrated relative risk (RR) or odds ratio estimates with 95%CI for the predictive risk of CRC by T2DM. Summary relative risks with 95%CI were analyzed by using an effects summary ratio model. Heterogeneity among studies was assessed by the Cochran’s Q and I2 statistics. RESULTS: The meta analysis of 8 finally selected studies showed a positive correlation of T2DM with the risk of CRC as depicted by effects summary RR of 1.21 (95%CI: 1.02-1.42). Diabetic women showed greater risk of developing CRC as their effect summary RR of 1.22 (95%CI: 1.01-49) with significant overall Z test at 5% level of significance was higher than the effect summary RR of 1.17 (95%CI: 1.00-1.37) of men showing insignificant Z test. The effect summary RR of 1.19 with 95%CI of 1.07-1.33 indicate a positive relationship between DM and increased risk of CRC with significant heterogeneity (I2 = 92% and P-value < 0.05). CONCLUSION: Results from this systematic review and meta-analysis report that diabetic people have an increased risk of CRC as compared to non-diabetics. PMID:26019469

  8. Double genomic control is not effective to correct for population stratification in meta-analysis for genome-wide association studies.

    PubMed

    Wang, Shudong; Chen, Wenan; Chen, Xiangning; Hu, Fengjiao; Archer, Kellie J; Liu, Hb Nianjun; Sun, Shumei; Gao, Guimin

    2012-01-01

    Meta-analysis of genome-wide association studies (GWAS) has become a useful tool to identify genetic variants that are associated with complex human diseases. To control spurious associations between genetic variants and disease that are caused by population stratification, double genomic control (GC) correction for population stratification in meta-analysis for GWAS has been implemented in the software METAL and GWAMA and is widely used by investigators. In this research, we conducted extensive simulation studies to evaluate the double GC correction method in meta-analysis and compared the performance of the double GC correction with that of a principal components analysis (PCA) correction method in meta-analysis. Results show that when the data consist of population stratification, using double GC correction method can have inflated type I error rates at a marker with significant allele frequency differentiation in the subpopulations (such as caused by recent strong selection). On the other hand, the PCA correction method can control type I error rates well and has much higher power in meta-analysis compared to the double GC correction method, even though in the situation that the casual marker does not have significant allele frequency difference between the subpopulations. We applied the double GC correction and PCA correction to meta-analysis of GWAS for two real datasets from the Atherosclerosis Risk in Communities (ARIC) project and the Multi-Ethnic Study of Atherosclerosis (MESA) project. The results also suggest that PCA correction is more effective than the double GC correction in meta-analysis. PMID:23269928

  9. The association between systemic sclerosis and bone mineral density- a meta-analysis of observational studies.

    PubMed

    Wan, Ya-Nan; Zhang, Li; Wang, Yu-Jie; Yan, Jun-Wei; Wang, Bing-Xiang; Wang, Jing

    2014-11-01

    Previous research has shown inconsistent effect of systemic sclerosis (SSc) on bone mineral density (BMD). The objective of this study was to perform a meta-analysis of previous articles to investigate the differences in BMD (g/cm(2) ) between SSc and non-SSc populations and to discuss potential underlying mechanisms. Twelve full-text articles (including an outlier study and two studies with identical data) with 662 SSc patients and 886 controls were identified by searching Medline prior to 10 September, 2013 using search terms 'Systemic sclerosis' OR 'scleroderma' and 'osteoporosis' OR 'bone density' OR 'bone mass'. BMD (mean and standard deviation), T-scores and Z-scores at lumbar spine, femoral neck and total hip measured by dual-energy X-ray absorptiometry were extracted. Meta-analysis showed that a lower level of BMD was found in SSc patients, with weighted mean difference of -0.343 (95% CI: -0.500 to -0.186) at femoral neck, -0.084 (95% CI: -0.110 to -0.057) at total hip and -0.104 (95% CI: -0.135 to -0.073) at the lumbar spine. We conclude that patients with SSc may have a lower BMD level than healthy controls. PMID:24894309

  10. Association between vitamin E and non-alcoholic steatohepatitis: a meta-analysis

    PubMed Central

    Xu, Renfan; Tao, Anyu; Zhang, Shasha; Deng, Youbin; Chen, Guangzhi

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) generally has a relatively favorable clinical course; however, non-alcoholic steatohepatitis (NASH) was much more frequently progresses to cirrhosis and hepatocellular carcinoma. We performed a systematic review and meta-analysis of clinical trials to examine the effects of vitamin E supplementation in improving liver histology in NASH. We performed a comprehensive search of the PubMed, Embase and Cochrane databases through October 2014. Weighted mean differences (WMDs) and their respective 95% confidence intervals (CIs) were calculated to assess the efficacy of vitamin E in improving liver histological scores by using fixed effects or random effects. Standard methods were performed to explore statistical heterogeneity and publication bias. Compared with controls, vitamin E supplementation significantly improved all histological parameters, including steatosis (WMD = -0.62, 95% CI: -0.95, -0.77, P = 0.0002), hepatocyte ballooning (WMD = -0.30, 95% CI: -0.56, -0.04, P = 0.03), lobular inflammation (WMD = -0.39, 95% CI: -0.67, -0.11, P = 0.007) and fibrosis (WMD = -0.39, 95% CI: -0.72, -0.06, P = 0.02). Our analysis also indicated the absence of publication bias between NASH and Vitamin E intake. This meta-analysis indicates that vitamin E supplementation had a significant and positive effect in the improvement of steatosis, ballooning degeneration, lobular inflammation and fibrosis in patients with NASH. PMID:26064294