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Sample records for association scan meta-analysis

  1. Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution

    PubMed Central

    Qi, Lu; Speliotes, Elizabeth K.; Thorleifsson, Gudmar; Willer, Cristen J.; Herrera, Blanca M.; Jackson, Anne U.; Lim, Noha; Scheet, Paul; Soranzo, Nicole; Amin, Najaf; Aulchenko, Yurii S.; Chambers, John C.; Drong, Alexander; Luan, Jian'an; Lyon, Helen N.; Rivadeneira, Fernando; Sanna, Serena; Timpson, Nicholas J.; Zillikens, M. Carola; Zhao, Jing Hua; Almgren, Peter; Bandinelli, Stefania; Bennett, Amanda J.; Bergman, Richard N.; Bonnycastle, Lori L.; Bumpstead, Suzannah J.; Chanock, Stephen J.; Cherkas, Lynn; Chines, Peter; Coin, Lachlan; Cooper, Cyrus; Crawford, Gabriel; Doering, Angela; Dominiczak, Anna; Doney, Alex S. F.; Ebrahim, Shah; Elliott, Paul; Erdos, Michael R.; Estrada, Karol; Ferrucci, Luigi; Fischer, Guido; Forouhi, Nita G.; Gieger, Christian; Grallert, Harald; Groves, Christopher J.; Grundy, Scott; Guiducci, Candace; Hadley, David; Hamsten, Anders; Havulinna, Aki S.; Hofman, Albert; Holle, Rolf; Holloway, John W.; Illig, Thomas; Isomaa, Bo; Jacobs, Leonie C.; Jameson, Karen; Jousilahti, Pekka; Karpe, Fredrik; Kuusisto, Johanna; Laitinen, Jaana; Lathrop, G. Mark; Lawlor, Debbie A.; Mangino, Massimo; McArdle, Wendy L.; Meitinger, Thomas; Morken, Mario A.; Morris, Andrew P.; Munroe, Patricia; Narisu, Narisu; Nordström, Anna; Nordström, Peter; Oostra, Ben A.; Palmer, Colin N. A.; Payne, Felicity; Peden, John F.; Prokopenko, Inga; Renström, Frida; Ruokonen, Aimo; Salomaa, Veikko; Sandhu, Manjinder S.; Scott, Laura J.; Scuteri, Angelo; Silander, Kaisa; Song, Kijoung; Yuan, Xin; Stringham, Heather M.; Swift, Amy J.; Tuomi, Tiinamaija; Uda, Manuela; Vollenweider, Peter; Waeber, Gerard; Wallace, Chris; Walters, G. Bragi; Weedon, Michael N.; Witteman, Jacqueline C. M.; Zhang, Cuilin; Zhang, Weihua; Caulfield, Mark J.; Collins, Francis S.; Davey Smith, George; Day, Ian N. M.; Franks, Paul W.; Hattersley, Andrew T.; Hu, Frank B.; Jarvelin, Marjo-Riitta; Kong, Augustine; Kooner, Jaspal S.; Laakso, Markku; Lakatta, Edward; Mooser, Vincent; Morris, Andrew D.; Peltonen, Leena; Samani, Nilesh J.; Spector, Timothy D.; Strachan, David P.; Tanaka, Toshiko; Tuomilehto, Jaakko; Uitterlinden, André G.; van Duijn, Cornelia M.; Wareham, Nicholas J.; Watkins for the PROCARDIS consortia, Hugh; Waterworth, Dawn M.; Boehnke, Michael; Deloukas, Panos; Groop, Leif; Hunter, David J.; Thorsteinsdottir, Unnur; Schlessinger, David; Wichmann, H.-Erich; Frayling, Timothy M.; Abecasis, Gonçalo R.; Hirschhorn, Joel N.; Loos, Ruth J. F.; Stefansson, Kari; Mohlke, Karen L.; Barroso, Inês; McCarthy for the GIANT consortium, Mark I.

    2009-01-01

    To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist–hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×10−11) and MSRA (WC, P = 8.9×10−9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10−8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity. PMID:19557161

  2. 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

    2016-03-29

    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.

  3. 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

  4. 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

    Festen, Eleonora A M; Goyette, Philippe; Green, Todd; 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

    2011-01-27

    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 x 10⁻⁵ in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value < 1 x 10⁻² in CelD and < 1 x 10⁻³ in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37 x 10⁻⁸ and 6.39 x 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 x 10⁻¹⁰ and 1.38 x 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

  5. 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.

  6. Cognitive Impairment Associated with Atrial Fibrillation: A Meta-analysis

    PubMed Central

    Kalantarian, Shadi; Stern, Theodore A.; Mansour, Moussa; Ruskin, Jeremy N.

    2015-01-01

    Background Atrial fibrillation (AF) has been linked with an increased risk of cognitive impairment and dementia. Purpose To complete a meta-analysis of studies examining the association between AF and cognitive impairment. Data Sources Electronic search of 5 large databases and hand search of article references. Study Selection Prospective and non-prospective studies reporting adjusted risk estimates for the relationship between AF and cognitive impairment. Data Extraction Two abstracters independently extracted data on study characteristics, risk estimates, methods of AF and outcome ascertainment, and methodological quality. Data Synthesis Twenty one studies were included in the meta-analysis. AF was significantly associated with a higher risk of cognitive impairment independent of stroke history (relative risk (RR) [95% confidence interval (CI)] =1.34 [1.13, 1.58]), in patients with first-ever or recurrent stroke (RR [95%] =2.7 [1.82, 4.00]) and in a broader population including patients with or without a history of stroke (RR [95% CI] =1.4 [1.19, 1.64]). However, there was significant heterogeneity among studies of the broader population (I2 =69.4 %). Limiting the analysis to prospective studies yielded similar results (RR [95% CI] =1.36 [1.12, 1.65]). Restricting the analysis to studies of dementia eliminated the significant heterogeneity (P value =0.137) but did not alter the pooled estimate substantially (RR [95% CI] = 1.38 [1.22, 1.56]). Limitations There is an inherent bias due to confounding variables in observational studies. There was significant heterogeneity among included studies. Conclusions Evidence suggests that AF is associated with a higher risk of cognitive impairment and dementia, with or without a history of clinical stroke. Further studies are required to elucidate the relationship between AF and subtypes of dementia as well as the etiology of cognitive impairment. PMID:23460057

  7. 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

  8. Association of Interleukin 10 Gene Polymorphisms with Autoimmune Thyroid Disease: Meta-Analysis.

    PubMed

    Jung, J H; Song, G G; Kim, J-H; Choi, S J

    2016-11-01

    The aim of this study was to perform a meta-analysis of eligible studies and to derive a precise estimate of the association between interleukin 10 (IL10) polymorphisms and susceptibility to autoimmune thyroid disease (AITD). Meta-analyses were conducted on the associations between AITD and the -1082 G/A (rs1800896), -819 C/T (rs1800871) and -592 C/A (rs1800872) polymorphisms in IL10, and the haplotype of these polymorphisms and AITD. A total of 2903 AITD patients and 3060 controls in 10 eligible studies were included in the meta-analysis. This meta-analysis showed significant associations between IL10 at the -1082 G allele and overall AITD (OR: 1.44, 95% CI 1.13-1.82, P = 0.003), but no association between the IL10 -592 C allele and the -819 C allele and AITD. Subgroup studies demonstrated significant associations between the -1082 G allele and susceptibility to Graves' disease. Ethnicity-specific meta-analysis revealed significant associations between the -1082 G allele and AITD susceptibility in Asian populations; however, in Middle Eastern populations, no association was evident. Meta-analysis of the IL10 haplotype revealed an association between the ATA haplotype and AITD (OR: 1.17, 95% CI 1.00-1.36, P = 0.04). Meta-analysis demonstrates that the IL10 polymorphisms are associated with susceptibility to AITD.

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

    PubMed

    Tang, Zheng-Zheng; Lin, Dan-Yu

    2015-07-02

    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.

  10. Molecular genetics of obsessive-compulsive disorder: a comprehensive meta-analysis of genetic association studies.

    PubMed

    Taylor, S

    2013-07-01

    Twin studies indicate that obsessive-compulsive disorder (OCD) is strongly influenced by additive genetic factors. Yet, molecular genetic association studies have yielded inconsistent results, possibly because of differences across studies in statistical power. Meta-analysis can yield greater power. This study reports the first comprehensive meta-analysis of the relationship between OCD and all previously examined polymorphisms for which there was sufficient information in the source studies to compute odds ratios (ORs). A total of 230 polymorphisms from 113 genetic association studies were identified. A full meta-analysis was conducted for 20 polymorphisms that were examined in 5 or more data sets, and a secondary meta-analysis (limited to the computation of mean effect sizes) was conducted for 210 polymorphisms that were examined in fewer than 5 data sets. In the main meta-analysis, OCD was associated with serotonin-related polymorphisms (5-HTTLPR and HTR2A) and, in males only, with polymorphisms involved in catecholamine modulation (COMT and MAOA). Nonsignificant trends were identified for two dopamine-related polymorphisms (DAT1 and DRD3) and a glutamate-related polymorphism (rs3087879). The secondary meta-analysis identified another 18 polymorphisms with significant ORs that merit further investigation. This study demonstrates that OCD is associated with multiple genes, with most having a modest association with OCD. This suggests a polygenic model of OCD, consistent with twin studies, in which multiple genes make small, incremental contributions to the risk of developing the disorder. Future studies, with sufficient power to detect small effects, are needed to investigate the genetic basis of OCD subtypes, such as early vs late onset OCD.

  11. Systematic review and meta-analysis estimating association of cysticercosis and neurocysticercosis with epilepsy

    PubMed Central

    Debacq, Gabrielle; Garcia, Héctor H.; Boumediene, Farid; Marin, Benoit; Ngoungou, Edgard B.; Preux, Pierre-Marie

    2017-01-01

    Background We reviewed studies that analyzed cysticercosis (CC), neurocysticercosis (NCC) and epilepsy across Latin America, Asia and Sub-Saharan Africa, to estimate the odds ratio and etiologic fraction of epilepsy due to CC in tropical regions. Methodology We conducted a systematic review of the literature on cysticercosis and epilepsy in the tropics, collecting data from case-control and cross-sectional studies. Exposure criteria for CC included one or more of the following: serum ELISA or EITB positivity, presence of subcutaneous cysts (both not verified and unverified by histology), histology consistent with calcified cysts, and brain CT scan consistent with NCC. A common odds-ratio was then estimated using meta-analysis. Principal findings 37 studies from 23 countries were included (n = 24,646 subjects, 14,934 with epilepsy and 9,712 without epilepsy). Of these, 29 were case-control (14 matched). The association between CC and epilepsy was significant in 19 scientific articles. Odds ratios ranged from 0.2 to 25.4 (a posteriori power 4.5–100%) and the common odds ratio was 2.7 (95% CI 2.1–3.6, p <0.001). Three subgroup analyses performed gave odds ratios as: 2.2 (EITB-based studies), 3.2 (CT-based studies), 1.9 (neurologist-confirmed epilepsy; door-to-door survey and at least one matched control per case). Etiologic fraction was estimated to be 63% in the exposed group among the population. Significance Despite differences in findings, this meta-analysis suggests that cysticercosis is a significant contributor to late-onset epilepsy in tropical regions around the world, and its impact may vary depending on transmission intensity. PMID:28267746

  12. 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…

  13. Advancing Maternal Age Is Associated with Increasing Risk for Autism: A Review and Meta-Analysis

    ERIC Educational Resources Information Center

    Sandin, Sven; Hultman, Christina M.; Kolevzon, Alexander; Gross, Raz; MacCabe, James H.; Reichenberg, Abraham

    2012-01-01

    Objective: We conducted a meta-analysis of epidemiological studies investigating the association between maternal age and autism. Method: Using recommended guidelines for performing meta-analyses, we systematically selected, and extracted results from, epidemiological scientific studies reported before January 2012. We calculated pooled risk…

  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 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...

  16. Meta-analysis of genome wide association studies for pork quality traits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Given the importance of pork quality in the meat processing industry, genome-wide association studies were performed for eight meat quality traits and also, a meta-analysis (MA) of GWA was implemented combining independent results from pig populations. Data from three pig datasets (USMARC, Commercia...

  17. Meta-analysis of sex-specific genome-wide association studies.

    PubMed

    Magi, Reedik; Lindgren, Cecilia M; Morris, Andrew P

    2010-12-01

    Despite the success of genome-wide association studies, much of the genetic contribution to complex human traits is still unexplained. One potential source of genetic variation that may contribute to this "missing heritability" is that which differs in magnitude and/or direction between males and females, which could result from sexual dimorphism in gene expression. Such sex-differentiated effects are common in model organisms, and are becoming increasingly evident in human complex traits through large-scale male- and female-specific meta-analyses. In this article, we review the methodology for meta-analysis of sex-specific genome-wide association studies, and propose a sex-differentiated test of association with quantitative or dichotomous traits, which allows for heterogeneity of allelic effects between males and females. We perform detailed simulations to compare the power of the proposed sex-differentiated meta-analysis with the more traditional "sex-combined" approach, which is ambivalent to gender. The results of this study highlight only a small loss in power for the sex-differentiated meta-analysis when the allelic effects of the causal variant are the same in males and females. However, over a range of models of heterogeneity in allelic effects between genders, our sex-differentiated meta-analysis strategy offers substantial gains in power, and thus has the potential to discover novel loci contributing effects to complex human traits with existing genome-wide association data.

  18. Children's Responses to Interparental Conflict: A Meta-Analysis of Their Associations with Child Adjustment

    ERIC Educational Resources Information Center

    Rhoades, Kimberly A.

    2008-01-01

    A meta-analysis examined the relations between children's adjustment and children's cognitive, affective, behavioral, and physiological responses to interparental conflict. Studies included children between 5 and 19 years of age. Moderate effect sizes were found for the associations between cognitions and internalizing and externalizing behavior…

  19. 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.

  20. Association between rhinovirus wheezing illness and the development of childhood asthma: a meta-analysis

    PubMed Central

    Liu, Lu; Pan, Yilin; Zhu, Yanting; Song, Yang; Su, Xiaofan; Yang, Lan; Li, Manxiang

    2017-01-01

    Objective The relation between early-life rhinovirus (RV) wheezing illness and later onset of wheezing/asthma remains a subject of debate. Therefore, we conducted this meta-analysis to evaluate the association between RV wheezing illness in the first 3 years of life and the subsequent development of wheezing/asthma. Design Systematic review and meta-analysis. Methods The PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were systematically searched for studies published between 1988 and February 2017, and additional studies were found by searching reference lists of relevant articles. 2 reviewers independently extracted data and assessed the quality of each study. Results were pooled using fixed-effect models or random-effects models as appropriate. Results The meta-analysis included 15 original articles which met the criteria, while 10 articles reported the results of 4 longitudinal cohort studies with different follow-up periods. RV wheezing illness in the first 3 years of life was associated with an increased risk of wheezing/asthma in later life (relative risk (RR)=2.00, 95% CI 1.62 to 2.49, p<0.001). In subgroup analysis by age at follow-up, the association still remained significant in <10 years (RR=2.02, 95% CI 1.70 to 2.39, p<0.001) and ≥10 years (RR=1.92, 95% CI 1.36 to 2.72, p<0.001). Conclusions The meta-analysis suggests an association between RV-induced wheezing in the first 3 years of life and the subsequent development of wheezing/asthma. Large-scale and well-designed studies that adequately address concerns for potential confounding factors are required to validate the risk identified in the current meta-analysis. PMID:28373249

  1. 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. PMID:27446866

  2. Association between susceptibility to rheumatoid arthritis and PADI4 polymorphisms: a meta-analysis.

    PubMed

    Lee, Young Ho; Bae, Sang-Cheol

    2016-04-01

    The objective of the study was to determine by meta-analysis whether polymorphisms of the gene encoding peptidylarginine deiminase 4 (PADI4) are associated with susceptibility to rheumatoid arthritis (RA). A literature review was conducted to identify data sets that described analyses of genetic association between PADI4 polymorphisms and RA. Data sets were collated and a meta-analysis was performed, with a specific focus on associations within Caucasian and Asian populations. A total of 15,947 RA cases and 22,696 controls that were taken from 28 studies in 24 papers were included in this study. Meta-analysis showed a significant association between allele 2 of the PADI4_94 polymorphism and RA in the overall population (odds ratio [OR] = 1.155, 95 % confidence interval [CI] = 1.069-1.249, p = 2.7 × 10(-5)). Stratification by ethnicity revealed an association between PADI4_94 allele 2 and RA in Asians (OR = 1.273, 95 % CI = 1.193-1.359, p < 1.0 × 10(-9)), but not in Caucasians (OR = 1.024, 95 % CI = 0.973-1.078, p = 0.358). However, meta-analysis using homozygote contrast showed an association between PADI4_94 allele 2 and RA in both Asians (OR = 2.311, 95 % CI = 1.1.858-2.875, p < 1.0 × 10(-9)) and Caucasians (OR = 1.523, 95 % CI = 1.157-2.004, p = 0.008). Meta-analysis also revealed an association between allele 2 of the PADI4_104 polymorphism and RA in both Asians (OR = 1.547, 95 % CI = 1.247-1.919, p = 7.1 × 10(-6)) and Caucasians (OR = 1.096, 95 % CI = 1.025-1.172, p = 0.008). Finally, meta-analysis showed an association between allele 2 of the PADI4_92 polymorphism and RA in Asians (OR = 1.263, 95 % CI = 1.153-1.384, p = 5.8 × 10(-8)), but not in Caucasians (OR = 1.123, 95 % CI = 0.980-1.287, p = 0.095). Meta-analysis indicated no association between allele 2 of either the PADI4_90 or PADI4_89 polymorphisms and RA in

  3. The association between human endogenous retroviruses and multiple sclerosis: A systematic review and meta-analysis

    PubMed Central

    Morandi, Elena; Tanasescu, Radu; Tarlinton, Rachael E.; Constantinescu, Cris S.; Zhang, Weiya; Tench, Christopher

    2017-01-01

    Background The interaction between genetic and environmental factors is crucial to multiple sclerosis (MS) pathogenesis. Human Endogenous Retroviruses (HERVs) are endogenous viral elements of the human genome whose expression is associated with MS. Objective To perform a systematic review and meta-analysis and to assess qualitative and quantitative evidence on the expression of HERV families in MS patients. Methods Medline, Embase and the Cochrane Library were searched for published studies on the association of HERVs and MS. Meta-analysis was performed on the HERV-W family. Odds Ratio (OR) and 95% confidence interval (CI) were calculated for association. Results 43 reports were extracted (25 related to HERV-W, 13 to HERV-H, 9 to HERV-K, 5 to HRES-1 and 1 to HER-15 family). The analysis showed an association between expression of all HERV families and MS. For HERV-W, adequate data was available for meta-analysis. Results from meta-analyses of HERV-W were OR = 22.66 (95%CI 6.32 to 81.20) from 4 studies investigating MSRV/HERV-W (MS-associated retrovirus) envelope mRNA in peripheral blood mononuclear cells, OR = 44.11 (95%CI 12.95 to 150.30) from 6 studies of MSRV/HERV-W polymerase mRNA in serum/plasma and OR = 6.00 (95%CI 3.35 to 10.74) from 4 studies of MSRV/HERV-W polymerase mRNA in CSF. Conclusions This systematic review and meta-analysis shows an association between expression of HERVs, and in particular the HERV-W family, and MS. PMID:28207850

  4. Associations between ERAP1 polymorphisms and susceptibility to ankylosing spondylitis: a meta-analysis.

    PubMed

    Lee, Young Ho; Song, Gwan Gyu

    2016-08-01

    The aim of this study was to determine whether 11 polymorphisms of endoplasmic reticulum aminopeptidase 1 (ERAP1) confer susceptibility to ankylosing spondylitis (AS). The authors conducted meta-analyses on associations between ERAP1 polymorphisms and AS susceptibility by using fixed and random effects models. A total of 19 articles were included in this meta-analysis, which comprised a total of 19,902 AS patients and 39,750 controls. The meta-analysis revealed a significant association between AS and the minor alleles of the rs30187 polymorphism in all study subjects (OR = 1.255, 95 % CI = 1.147-1.373, P = 8.0 × 10(-8)). Stratification by ethnicity led to the identification of a significant association between this polymorphism and AS in European patients (OR = 1.283, 95 % CI = 1.237-1.331, P < 1.0 × 10(-9)). Meta-analyses of the results for the rs27044, rs10050860, rs2287987, rs17482078, and rs26653 polymorphisms showed the same pattern that was found for rs30187. Interestingly, the rs27037 polymorphism was significantly associated with AS susceptibility in both European and Asian patients. Meta-analysis showed a significant association between AS and the minor alleles of the rs27980 and rs27582 polymorphisms in the East Asian patients (OR = 0.904, 95 % CI = 0.818-0.999, P = 0.047; OR = 0.871, 95 % CI = 0.772-0.982, P = 0.024, respectively) (Table 2). However, these polymorphisms have not been studied in Europeans. This meta-analysis shows that the ERAP1 polymorphisms are associated with the development of AS in Europeans and East Asians.

  5. Association between Lutein and Zeaxanthin Status and the Risk of Cataract: A Meta-Analysis

    PubMed Central

    Liu, Xiao-Hong; Yu, Rong-Bin; Liu, Rong; Hao, Zhen-Xuan; Han, Cheng-Cheng; Zhu, Zhong-Hai; Ma, Le

    2014-01-01

    The purpose of this meta-analysis was to evaluate the relationship between blood lutein and zeaxanthin concentration and the risk of age-related cataract (ARC). MEDLINE, EMBASE, ISI and Cochrane Library were searched to identify relevant studies up to April 2013. Meta-analysis was conducted to obtain pooled relative risks (RRs) for the highest-versus-lowest categories of blood lutein and zeaxanthin concentrations. One cohort study and seven cross-sectional studies were included in the meta-analysis. There were significant inverse associations between nuclear cataract and blood lutein and zeaxanthin concentrations, with the pooled RRs ranging from 0.63 (95% confidence interval (CI): 0.49, 0.77) for zeaxanthin to 0.73 (95% CI: 0.59, 0.87) for lutein. A stronger association between nuclear cataract and blood zeaxanthin might be noted for the studies conducted in the European Nations. Blood lutein and zeaxanthin were also noted to lead towards a decrease in the risk of cortical cataract and subcapsular cataract; however, these pooled RRs were not statistically significant, with the exception of a marginal association between lutein and subcapsular cataract. Our results suggest that high blood lutein and zeaxanthin are significantly associated with a decrease in the risk of nuclear cataract. However, no significant associations were found for ARC in other regions of the lens. PMID:24451312

  6. Vancomycin-associated nephrotoxicity: A meta-analysis of administration by continuous versus intermittent infusion.

    PubMed

    Hanrahan, Timothy; Whitehouse, Tony; Lipman, Jeffrey; Roberts, Jason A

    2015-09-01

    Vancomycin is a glycopeptide antibiotic widely used in the management of meticillin-resistant Staphylococcus aureus (MRSA). Guidelines currently recommend vancomycin be administered by intermittent infusion, despite recent research suggesting that continuous infusion (CI) may be associated with lower rates of vancomycin-associated nephrotoxicity. In 2012, Cataldo et al. presented a meta-analysis supporting the use of CI. Here we present an updated meta-analysis, inclusive of a recently published large-scale retrospective study. PubMed, EMBASE and Cochrane Reviews databases were searched using the keywords 'vancomycin' and 'continuous' or 'intermittent' or 'infusion' or 'discontinuous' or 'administration'. Seven studies were included in the final analysis. Using a random-effects model, a non-significant trend of reduced nephrotoxicity in those who received vancomycin by CI (risk ratio=0.799, 95% confidence interval 0.523-1.220; P=0.299) was identified. A large, randomised controlled trial is necessary to confirm these results.

  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.

  8. 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.

  9. Association between CHFR gene hypermethylation and gastric cancer risk: a meta-analysis

    PubMed Central

    Shi, Hua; Wang, Xiaojing; Wang, Jianbo; Pan, Jundi; Liu, Junwei; Ye, Bin

    2016-01-01

    Background The association between the hypermethylation of CHFR gene and gastric cancer risk has been investigated by a number of studies. However, the sample size of the majority of these studies was very small. To get a more a convincing conclusion, here we performed a meta-analysis of the previously published studies to assess the association between CHFR methylation and the risk of gastric cancer. Methods Eligible studies were identified by searching the MEDLINE/PubMed, Embase, and Web of Science databases before May 2016 without any language restriction. The strength of the association was estimated by odds ratio with its 95% confidence interval (CI). Results Totally 1,399 samples, including 758 gastric cancer cases and 641 controls, from 13 studies were included in the present meta-analysis. Compared with non-cancer controls, the pooled OR of CHFR methylation in gastric cancer patients was 9.08 (95% CI: 6.40–12.88, P<0.001), suggesting that the methylation of CHFR was significantly associated with increased risk of gastric cancer. Similar results were observed when subgroup analyses were performed stratified by country, ethnicity, and methylation testing methods. Conclusion Our meta-analysis showed a strong positive correlation between CHFR methylation and risk of gastric cancer, suggesting that CHFR methylation might be a promising biomarker for the diagnosis of gastric cancer. PMID:27994471

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

    PubMed Central

    Li, Bao-Sheng

    2016-01-01

    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

  11. Association of insulin degrading enzyme gene polymorphisms with Alzheimer's disease: a meta-analysis.

    PubMed

    Cheng, Huawei; Wang, Lin; Shi, Tianlu; Shang, Yuping; Jiang, Ling

    2015-05-01

    Alzheimer's disease (AD) is a chronic degenerative disorder. It is caused by both genetic and environmental factors. The association of Insulin Degrading Enzyme (IDE) genotypes rs4646953, rs2251101 and rs1544210 with AD has been detected, but the findings were conflicted, however, Apolipoprotein-E (APOE)-ε4 allele has been observed as a genetic risk factor for AD. To investigate the issue, a meta-analysis was performed. We searched PubMed, Springer Link, AlzGene and CNKI for relevant literatures published by June 2013. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to explore the significant association. A total of 11 studies comprising 5771 cases and 5474 controls were considered in final meta-analysis. We found that weak connections existed between rs4646953 (TT vs. CC: z = 2.24, p = 0.025, OR = 1.536) and AD, but no significant associations have been found between other IDE gene single nucleotide polymorphisms of rs4646953, rs2251101 and rs1544210 with AD. We certified that APOE-ε4 allele was still be a suspected factor to AD. There was no evidence for obvious publication bias in overall meta-analysis. Furthermore, larger-scale randomized controlled trials are necessary to validate the association between IDE gene polymorphisms with AD.

  12. A meta-analysis of association between acne vulgaris and Demodex infestation.

    PubMed

    Zhao, Ya-E; Hu, Li; Wu, Li-Ping; Ma, Jun-Xian

    2012-03-01

    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 42130 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 18477, suggesting that at least 18477 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.

  13. Meta-analysis in the association between obesity and risk of thyroid cancer

    PubMed Central

    Zhang, Wei; Bai, Xiyong; Ge, Huai’e; Cui, Haibin; Wei, Zhijiang; Han, Guoda

    2014-01-01

    Although many epidemiologic studies have investigated obesity and thyroid cancer risk, definite conclusions cannot be drawn. To clarify the effects of obesity on the risk of thyroid cancer, a meta-analysis was performed. Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) till 16 Aug 2014. Pooled RRs and 95% CIs were used to assess the strength of the associations. A total of 16 studies including 12616154 subjects were involved in this meta-analysis. A significantly elevated thyroid cancer risk was found in overall analysis (RR = 1.29, 95% CI 1.20-1.37, P < 0.00001). In the gender subgroup analyses, a statistically significant association was found in male patients (RR = 1.35, 95% CI 1.16-1.58, P = 0.0001) and in female patients (RR = 1.29, 95% CI 1.19-1.40, P < 0.00001). When we limited the meta-analysis to studies that controlled for age (RR = 1.34, 95% CI 1.24-1.44, P < 0.00001), smoke (RR = 1.36, 95% CI 1.22-1.52, P < 0.00001), alcohol use (RR = 1.40, 95% CI 1.15-1.71, P = 0.0009), and history of benign thyroid disease (RR = 1.51, 95% CI 1.24-1.83, P < 0.0001), a significant association between obesity and thyroid cancer risk remained. This meta-analysis provides the evidence that obesity may contribute to the thyroid cancer development. PMID:25664030

  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. The association of Raynaud's syndrome with rheumatoid arthritis--a meta-analysis.

    PubMed

    Hartmann, Peter; Mohokum, Melvin; Schlattmann, Peter

    2011-08-01

    Rheumatoid arthritis (RA) has traditionally been included among the diseases associated with Raynaud's syndrome (RS). The prevalence of RS in patients with RA is not well defined. The objective of this paper was to assess the prevalence of RS in patients with RA-a meta-analysis of published data was performed. The PubMed database of the National Library of Medicine and ISI Web of Knowledge was used for studies dealing with RS and RA. The studies provided sufficient data to estimate the prevalence of RS in patients with RA. A forest plot was determined by the revealed prevalences. Statistical analysis was based on methods for a random effects meta-analysis and a finite mixture model for proportions. Publication bias was investigated with the linear regression test (Egger's method). A meta-regression was conducted by the year of publication. Twenty-eight eligible studies, contributing data on 3,730 subjects, were included in this meta-analysis. For RA, a pooled prevalence of 12.3% and 95% CI = 0.093-0.157 were obtained. A mixture model analysis found five latent classes. Statistically and graphically, publication bias was present (p = 0.031). In the meta-regression, the estimated prevalence decreased within the observation period (1977-2010) from 11.2% to 9.4%. Despite some heterogeneity, there is a possible indication of an association for RS and patients with RA.

  16. A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder.

    PubMed

    Wang, Ke-Sheng; Liu, Xue-Feng; Aragam, Nagesh

    2010-12-01

    Schizophrenia and bipolar disorder both have strong inherited components. Recent studies have indicated that schizophrenia and bipolar disorder may share more than half of their genetic determinants. In this study, we performed a meta-analysis (combined analysis) for genome-wide association data of the Affymetrix Genome-Wide Human SNP array 6.0 to detect genetic variants influencing both schizophrenia and bipolar disorder using European-American samples (653 bipolar cases and 1034 controls, 1172 schizophrenia cases and 1379 controls). The best associated SNP rs11789399 was located at 9q33.1 (p=2.38 × 10(-6), 5.74 × 10(-4), and 5.56 × 10(-9), for schizophrenia, bipolar disorder and meta-analysis of schizophrenia and bipolar disorder, respectively), where one flanking gene, ASTN2 (220kb away) has been associated with attention deficit/hyperactivity disorder and schizophrenia. The next best SNP was rs12201676 located at 6q15 (p=2.67 × 10(-4), 2.12 × 10(-5), 3.88 × 10(-8) for schizophrenia, bipolar disorder and meta-analysis, respectively), near two flanking genes, GABRR1 and GABRR2 (15 and 17kb away, respectively). The third interesting SNP rs802568 was at 7q35 within CNTNAP2 (p=8.92 × 10(-4), 1.38 × 10(-5), and 1.62 × 10(-7) for schizophrenia, bipolar disorder and meta-analysis, respectively). Through meta-analysis, we found two additional associated genes NALCN (the top SNP is rs2044117, p=4.57 × 10(-7)) and NAP5 (the top SNP is rs10496702, p=7.15 × 10(-7)). Haplotype analyses of above five loci further supported the associations with schizophrenia and bipolar disorder. These results provide evidence of common genetic variants influencing schizophrenia and bipolar disorder. These findings will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in schizophrenia and bipolar disorder.

  17. Association of citalopram with congenital anomalies: A meta-analysis

    PubMed Central

    Kang, Hyun-Hye; Ahn, Ki Hoon; Kwon, Bo Yong; Lee, Eun Hee; Lee, Ji-Sung; Oh, Min-Jeong; Kim, Hai-Joong

    2017-01-01

    Objective The antenatal use of citalopram, a widely prescribed selective serotonin reuptake inhibitor, has been suspected to be associated with congenital, particularly cardiac, anomalies. This study aimed to prove the association between citalopram use and congenital anomalies. Methods We searched the English literature from July 1998 to July 2015, by using the search terms ‘ citalopram’, ‘ pregnancy’, ‘ birth defects’, ‘ congenital anomalies’, and ‘ malformations’ in PubMed, Embase, Web of Science, and the Cochrane Library. Results Eight eligible articles were analyzed including a total of 1,507,896 participants. The odds ratio (OR) of major malformations associated with citalopram use during pregnancy was 1.07 (95% confidence interval [CI], 0.98 to 1.17). Concerning cardiac malformations, the OR for all included studies was 1.31 (95% CI, 0.88 to 1.93). The analysis of cardiac malformations was repeated to reduce heterogeneity after excluding one outlier study (OR, 1.03; 95% CI, 0.84 to 1.26). Conclusion From our data, it can be concluded that citalopram use is not associated with major birth defects. However, physicians should carefully weigh the benefits against the potential risks of citalopram use, and counsel patients accordingly. PMID:28344955

  18. 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

  19. Association of LPP and TAGAP Polymorphisms with Celiac Disease Risk: A Meta-Analysis

    PubMed Central

    Huang, Shi-Qi; Zhang, Na; Zhou, Zi-Xing; Huang, Chui-Can; Zeng, Cheng-Li; Xiao, Di; Guo, Cong-Cong; Han, Ya-Jing; Ye, Xiao-Hong; Ye, Xing-Guang; Ou, Mei-Ling; Zhang, Bao-Huan; Liu, Yang; Zeng, Eddy Y.; Yang, Guang; Jing, Chun-Xia

    2017-01-01

    Background: Lipoma preferred partner (LPP) and T-cell activation Rho GTPase activating protein (TAGAP) polymorphisms might influence the susceptibility to celiac disease. Therefore, we performed a meta-analysis by identifying relevant studies to estimate the risks of these polymorphisms on celiac disease. Methods: The PubMed, Web of Science and Embase databases were searched (up to October 2016) for LPP rs1464510 and TAGAP rs1738074 polymorphisms. Results: This meta-analysis included the same 7 studies for LPP rs1464510 and TAGAP rs1738074. The minor risk A allele at both rs1464510 and rs1738074 carried risks (odds ratios) of 1.26 (95% CI: 1.22–1.30) and 1.17 (95% CI: 1.14–1.21), respectively, which contributed to increased risks in all celiac disease patients by 10.72% and 6.59%, respectively. The estimated lambdas were 0.512 and 0.496, respectively, suggesting that a co-dominant model would be suitable for both gene effects. Conclusions: This meta-analysis provides robust estimates that polymorphisms in LPP and TAGAP genes are potential risk factors for celiac disease in European and American. Prospective studies and more genome-wide association studies (GWAS) are needed to confirm these findings, and some corresponding molecular biology experiments should be carried out to clarify the pathogenic mechanisms of celiac disease. PMID:28208589

  20. RUNX3 Promoter Methylation Is Associated with Hepatocellular Carcinoma Risk: A Meta-Analysis.

    PubMed

    Zhang, Xueyan; He, Hairong; Zhang, Xu; Guo, Wenjie; Wang, Yueqi

    2015-04-01

    Runt-related transcription factor 3 (RUNX3) has been reported to be a tumor-suppressing gene in hepatocellular carcinoma. Association between hepatocellular carcinoma and RUNX3 promoter methylation has been investigated in studies with specific ethnic backgrounds and small sample sizes. In this study, a meta-analysis was adopted to combine the data from 11 studies of association between RUNX3 promoter methylation and hepatocellular carcinoma. Pooled odds ratio for RUNX3 promoter methylation status in hepatocellular carcinoma versus control liver tissue was 24.37 (95%CI: 12.14, 48.92), p < .00001, indicates a strong association between methylation of the RUNX3 promoter and hepatocellular carcinoma.

  1. Factors Associated with Loss of Penicillin G Concentrations in Serum After Intramuscular Benzathine Penicillin G Injection: A Meta-analysis

    DTIC Science & Technology

    2012-07-01

    Naval Health Research Center Factors Associated With Loss of Penicillin G Concentrations in Serum After Intramuscular Benzathine Penicillin G... Serum After Intramuscular Benzathine Penicillin G Injection: A Meta-analysis 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...Concentrations in  Serum  After Intramuscular Benzathine  Penicillin  G Injection:  A Meta-analysis Michael P. Broderick, PhD,* Christian J. Hansen, BS,* and Dennis

  2. 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

    2014-10-28

    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.

  3. Associations between Interleukin-1 Gene Polymorphisms and Coronary Heart Disease Risk: A Meta-Analysis

    PubMed Central

    Zhou, Liang; Cai, Jianguang; Liu, Gang; Wei, Yuan; Tang, Hui

    2012-01-01

    Objective A great number of studies regarding the associations between IL-1B-511, IL-1B+3954 and IL-1RN VNTR polymorphisms within the IL-1gene cluster and coronary heart disease (CHD) have been published. However, results have been inconsistent. In this study, a meta-analysis was performed to investigate the associations. Methods Published literature from PubMed and Embase databases were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed- effect model. Results Thirteen studies (3,219 cases/2,445 controls) for IL-1B-511 polymorphism, nine studies (1,828 cases/1,818 controls) for IL-1B+3954 polymorphism and twelve studies (2,987 cases/ 2,208 controls) for IL-1RN VNTR polymorphism were included in this meta analysis. The results indicated that both IL-1B-511 and IL-1B+3954 polymorphisms were not associated with CHD risk (IL-1B-511 T vs. C: OR = 0.98, 95%CI 0.87–1.09; IL-1B+3954 T vs. C: OR = 1.06, 95%CI 0.95–1.19). Similarly, there was no association between IL-1RN VNTR polymorphism and CHD risk (*2 vs. L: OR = 1.00, 95%CI 0.85–1.17). Conclusions This meta-analysis suggested that there were no associations between IL-1 gene cluster polymorphisms and CHD. PMID:23029154

  4. Survivin Overexpression Is Associated with Aggressive Clinicopathological Features in Cervical Carcinoma: A Meta-Analysis

    PubMed Central

    Cheng, Ke-yan; Wang, Zhi-lian; Gu, Qian-yun; Hao, Min

    2016-01-01

    Objective Overexpression of survivin has been reported in many human tumors. However, the clinicopathological features associated with survivin overexpression in cervical carcinoma remain controversial. Thus, the current meta-analysis was performed to assess the clinicopathological significance of survivin in cervical carcinoma. Methods PubMed, EMBASE, and Web of Science databases were searched for relevant studies published through November 1, 2015. A meta-analysis was performed to evaluate the association between survivin expression and clinicopathological outcome in cervical carcinoma. Results Eleven eligible studies with a total of 865 patients were included. Survivin overexpression was closely related to lymph node metastasis (odds ratio [OR] = 0.679, 95% confidence interval [CI]: 0.509–0.905, P = 0.008) but was not significantly associated with tumor FIGO stage (I+II vs. III+IV) (OR = 0.843, 95% CI: 0.626–1.137, P = 0.264), tumor grade (G1+G2 vs. G3) (OR = 0.913, 95% CI: 0.689–1.210, P = 0.527), tumor size (>4 vs. ≤4 cm) (OR = 0.825, 95% CI: 0.434–1.570, P = 0.559), or stromal involvement (OR = 0.820, 95% CI: 0.545–1.233, P = 0.340). The correlation between survivin expression and overall survival was evaluated among a total of 238 patients from three eligible studies. The pooled HR was 1.129 (95% CI: 0.597–1.661; P = 0.000), indicating that survivin expression was significantly associated with poor survival in cervical carcinoma. Conclusions Based on the current meta-analysis, survivin is strongly associated with lymph node metastasis and poor prognosis. Additionally, survivin is a novel clinicopathological marker of cervical carcinoma and thus may be a therapeutic target for cervical carcinoma. PMID:27764228

  5. 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.

  6. Association of maternal education with the neuroblastoma susceptibility in children: a meta-analysis.

    PubMed

    Wang, Peng; Liao, Ning; Liao, Xin-Hong; Liang, Bing; Huang, Chun-Xia; Li, Wei

    2013-02-01

    Maternal education might be an important factor for the neuroblastoma risk in children, but it was conflicting. This meta-analysis was performed to evaluate the relationship between maternal education and neuroblastoma susceptibility and to explore whether maternal education was an important indicator to be associated with the neuroblastoma risk in children. The association studies were identified from the databases of PubMed, and Cochrane Library as of June 1, 2012, and eligible investigations were synthesized using meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. Six literatures were identified for the analysis of association between maternal education and neuroblastoma susceptibility in children, consisting of 2063 patients with cancer and 13,925 controls. There was no a marked association between maternal education and neuroblastoma susceptibility when the maternal education was less than high school (OR = 0.66, 95% CI: 0.43-1.01, P = .06). We also found that maternal education was not associated with the neuroblastoma susceptibility when the maternal education was high school (OR = 0.74, 95% CI: 0.31-1.75, P = .49) and more than high school (OR = 0.78, 95% CI: 0.33-1.85, P = .58). In conclusion, maternal education is not associated with the neuroblastoma susceptibility in children. However, more investigations are required to further clarify the association of maternal education with the neuroblastoma susceptibility in children.

  7. Association between the CYP1B1 polymorphisms and risk of cancer: a meta-analysis.

    PubMed

    Liu, Jie-Ying; Yang, Yu; Liu, Zhi-Zhong; Xie, Jian-Jun; Du, Ya-Ping; Wang, Wei

    2015-04-01

    The previous, published data on the association between CYP1B1 polymorphisms and cancer risk remained controversial. To derive a more precise estimation of the association between the CYP1B1 polymorphisms and cancer risk, we performed a meta-analysis to investigate the association between cancer susceptibility and CYP1B1 Leu432Val, Asn453Ser, Arg48Gly, and Ala119Ser polymorphisms. For Asn453Ser and Arg48Gly polymorphisms, significantly decreased endometrial cancer was observed among Caucasians. For Ala119Ser polymorphism, we found that individuals with the minor variant genotypes had a high risk of prostate cancer. For Leu432Val polymorphism, we found that individuals with the minor variant genotypes had a higher risk of endometrial cancer and lung cancer and had a lower risk of ovarian cancer. In summary, this meta-analysis suggests that Leu432Val polymorphism is associated with ovarian cancer, lung cancer, and endometrial cancer risk; Asn453Ser and Arg48Gly polymorphisms are associated with endometrial cancer risk among Caucasians, Ala119Ser polymorphism is associated with prostate cancer risk, and Ala119Ser polymorphism is associated with breast cancer risk in Caucasians. In addition, our work also points out the importance of new studies for Ala119Ser polymorphism in endometrial cancer, because high heterogeneity was observed (I (2) > 75 %).

  8. Digoxin-associated mortality: a systematic review and meta-analysis of the literature.

    PubMed

    Vamos, Mate; Erath, Julia W; Hohnloser, Stefan H

    2015-07-21

    There are conflicting data regarding the effect of digoxin use on mortality in patients with atrial fibrillation (AF) or with congestive heart failure (CHF). The aim of this meta-analysis was to provide detailed analysis of the currently available study reports. We performed a MEDLINE and a COCHRANE search (1993-2014) of the English literature dealing with the effects of digoxin on all-cause-mortality in subjects with AF or CHF. Only full-sized articles published in peer-reviewed journals were considered for this meta-analysis. A total of 19 reports were identified. Nine reports dealt with AF patients, seven with patients suffering from CHF, and three with both clinical conditions. Based on the analysis of adjusted mortality results of all 19 studies comprising 326 426 patients, digoxin use was associated with an increased relative risk of all-cause mortality [Hazard ratio (HR) 1.21, 95% confidence interval (CI), 1.07 to 1.38, P < 0.01]. Compared with subjects not receiving glycosides, digoxin was associated with a 29% increased mortality risk (HR 1.29; 95% CI, 1.21 to 1.39) in the subgroup of publications comprising 235 047 AF patients. Among 91.379 heart failure patients, digoxin-associated mortality risk increased by 14% (HR 1.14, 95% CI, 1.06 to 1.22). The present systematic review and meta-analysis of all available data sources suggest that digoxin use is associated with an increased mortality risk, particularly among patients suffering from AF.

  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. 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.

  11. 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.

  12. 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

  13. 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

  14. Association of COMT Val158Met polymorphism and breast cancer risk: an updated meta-analysis

    PubMed Central

    2012-01-01

    Background Catechol-O-methyltransferase (COMT) is one of the most important enzymes involved in estrogen metabolism and its functional genetic polymorphisms may be associated with breast cancer (BC) risk. Many epidemiological studies have been conducted to explore the association between the COMT Val158Met polymorphism and breast cancer risk. However, the results remain inconclusive. In order to derive a more precise estimation of this relationship, a large meta-analysis was performed in this study. Methods Systematic searches of the PubMed, Embase and Cochrane Library were performed. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association. Results A total of 56 studies including 34,358 breast cancer cases and 45,429 controls were included. Overall, no significant associations between the COMT Val158Met polymorphism and breast cancer risk were found for LL versus HH, HL versus HH, LL versus HL, recessive model LL versus HL+HH, and dominant model LL+HL versus HH. In subgroup analysis by ethnicity, source of controls, and menopausal status, there was still no significant association detected in any of the genetic models. Conclusion Our meta-analysis results suggest that the COMT Val158Met polymorphism may not contribute to breast cancer susceptibility. Virtual slides The virtual slides(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs4806123577708417 PMID:23039364

  15. The association of Raynaud's syndrome with carpal tunnel syndrome: a meta-analysis.

    PubMed

    Hartmann, Peter; Mohokum, Melvin; Schlattmann, Peter

    2012-03-01

    Carpal tunnel syndrome (CTS) has traditionally been included among the diseases associated with Raynaud's syndrome (RS). The prevalence of RS in patients suffering from CTS is not well defined. The objective of this paper was to assess the prevalence of RS in patients with CTS-a meta-analysis of published data was performed. The PubMed database of the National Library of Medicine and ISI Web of Knowledge was used for studies dealing with RS and CTS. The studies provided sufficient data to estimate the prevalence of RS in patients of CTS. A forest plot was determined by the revealed prevalence. Statistical analysis was based on methods for a random effects meta-analysis and a finite mixture model for proportions. Publication bias was investigated with the linear regression test (Egger's method). A meta-regression was conducted by the year of publication. Eight eligible studies, contributing data on 675 subjects, were included in this meta-analysis. For CTS, a pooled prevalence of 15.5% and 95% CI (95% CI 0.043, 0.318) were obtained. Statistically publication bias was present (P value 0.143). A mixture model analysis found five latent classes. The meta-regression indicated that the estimated prevalence increased when the year of commencement increased, too. Within the decade (1957-1967), the odds ratio increased from 1 (95% CI 1.065, 1.112) to 2.340 (95% CI 1.886, 2.903). Despite some heterogeneity, there is a possible indication of an association between RS and patients with CTS.

  16. Multivariate Meta-Analysis of Genetic Association Studies: A Simulation Study.

    PubMed

    Neupane, Binod; Beyene, Joseph

    2015-01-01

    In a meta-analysis with multiple end points of interests that are correlated between or within studies, multivariate approach to meta-analysis has a potential to produce more precise estimates of effects by exploiting the correlation structure between end points. However, under random-effects assumption the multivariate estimation is more complex (as it involves estimation of more parameters simultaneously) than univariate estimation, and sometimes can produce unrealistic parameter estimates. Usefulness of multivariate approach to meta-analysis of the effects of a genetic variant on two or more correlated traits is not well understood in the area of genetic association studies. In such studies, genetic variants are expected to roughly maintain Hardy-Weinberg equilibrium within studies, and also their effects on complex traits are generally very small to modest and could be heterogeneous across studies for genuine reasons. We carried out extensive simulation to explore the comparative performance of multivariate approach with most commonly used univariate inverse-variance weighted approach under random-effects assumption in various realistic meta-analytic scenarios of genetic association studies of correlated end points. We evaluated the performance with respect to relative mean bias percentage, and root mean square error (RMSE) of the estimate and coverage probability of corresponding 95% confidence interval of the effect for each end point. Our simulation results suggest that multivariate approach performs similarly or better than univariate method when correlations between end points within or between studies are at least moderate and between-study variation is similar or larger than average within-study variation for meta-analyses of 10 or more genetic studies. Multivariate approach produces estimates with smaller bias and RMSE especially for the end point that has randomly or informatively missing summary data in some individual studies, when the missing data

  17. Association between RASSF1A promoter methylation and renal cell cancer susceptibility: a meta-analysis.

    PubMed

    Huang, Y Q; Guan, H; Liu, C H; Liu, D C; Xu, B; Jiang, L; Lin, Z X; Chen, M

    2016-04-25

    Epigenetic inactivation of Ras-associated domain family 1A (RASSF1A) by hyper-methylation of its promoter region has been identified in various cancers. However, the role of RASSF1A in renal cancer has neither been thoroughly investigated nor reviewed. In this study, we reviewed and performed a meta-analysis of 13 published studies reporting correlations between methylation frequency of the RASSF1A promoter region and renal cancer risk. The odds ratios (ORs) of eligible studies and their corresponding 95% confidence intervals (95%CIs) were used to correlate RASSF1A promoter methylation with renal cell cancer risk and clinical or pathological variables, respectively. RASSF1A promoter methylation was significantly associated with the risk of renal cell cancer (OR = 19.35, 95%CI = 9.57-39.13). RASSF1A promoter methylation was significantly associated with pathological tumor grade (OR = 3.32, 95%CI = 1.55-7.12), and a possible positive correlation between RASSF1A promoter methylation status and tumor stage was noted (OR = 1.89, 95%CI = 1.00-3.56, P = 0.051). Overall, this meta-analysis demonstrated that RASSF1A promoter methylation is significantly associated with increased risk of renal cell cancer. RASSF1A promoter methylation frequency was positively correlated with pathological tumor grade, but not the clinical stage. This study showed that RASSF1A promoter methylation could be utilized to predict renal cell cancer prognosis.

  18. 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

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

    PubMed

    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; Rivadeneira, 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, W James; 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

    2012-05-01

    Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 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 newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).

  20. 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

  1. COL1A1 association and otosclerosis: a meta-analysis.

    PubMed

    Schrauwen, Isabelle; Khalfallah, Ayda; Ealy, Megan; Fransen, Erik; Claes, Charlotte; Huber, Alex; Murillo, Laura Rodriguez; Masmoudi, Saber; Smith, Richard J H; Van Camp, Guy

    2012-05-01

    Otosclerosis is a disease of abnormal bone remodeling in the human otic capsule that can lead to progressive hearing loss. Little of the underlying disease etiology has been elucidated thus far, although several studies have suggested that COL1A1 may play a role based on its importance in bone metabolism and other diseases like osteoporosis and osteogenesis imperfecta. Genetic association studies between COL1A1 and otosclerosis, however, have been contradictory. To resolve this issue, we studied a large Belgian-Dutch and a Swiss population for a genetic association between COL1A1 and otosclerosis and additionally performed a meta-analysis to investigate the overall genetic effect of COL1A1 on all otosclerosis populations studied to date. We found a significant association both in the Belgian-Dutch population and in the meta-analysis. In aggregate, our analysis supports evidence for an association between COL1A1 and otosclerosis although effect sizes of the variants reported in the initial studies are likely to be an overestimate of true effect sizes.

  2. 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

  3. Association between XRCC3 T241M polymorphism and glioma risk: a meta-analysis.

    PubMed

    Feng, Yiping; Zeng, Miaoyu; Xu, Qingsheng

    2014-06-01

    X-ray repair cross-complementing group 3 (XRCC3) plays a critical role in homologous recombination repair (HRR) accounting for repair of DNA double-strand breaks (DSB). Attention has been drawn upon the association of XRCC3 T241M polymorphism with glioma risk. The present meta-analysis aimed to examine whether XRCC3 T241M polymorphism was associated with glioma risk. Eligible articles were identified for the period up to March 2013. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were appropriately derived from fixed effects or random effects models. Eight case-control studies with a total of 3,455 glioma cases and 4,435 controls were included. Overall, no significant association between XRCC3 T241M polymorphism and glioma was found. In subgroup analysis, this polymorphism seemed to be associated with elevated glioma risk in Asians. No publication bias was detected. This meta-analysis suggested that XRCC3 T241M polymorphism did not confer glioma risk.

  4. Association between serum ferritin levels and metabolic syndrome: an updated meta-analysis

    PubMed Central

    Jin, Yuelong; He, Lianping; Chen, Yi; Fang, Yun; Yao, Yingshui

    2015-01-01

    It is definite that the serum iron level has a positive correlation with the risk of obesity. However, the association between increased serum ferritin levels and the metabolic syndrome still remains controversial. The purpose of this meta-analysis is to confirm the association between serum ferritin levels and metabolic syndrome. We searched PubMed and the China National Knowledge Infrastructure (CNKI) for relevant articles that assessed the association between serum ferritin levels and metabolic syndrome and were published between 2006 and 2014. Review Manage 5.3 software was used to collect and analysis the data cited in the ultimately selected papers. The variance was exhibited using the forest plot and the heterogeneity among studies was examined using the I2 index. We use the funnel plot to evaluate the publication bias. Cross-sectional study, case-control study and prospective cohort study met our inclusion criteria including data from a total of 4,797 participants. The pooled odds ratio (OR) for the metabolic syndrome comparing the highest and lowest category of ferritin levels was 1.20 (95% CI: 0.69, 1.71; I2=96%). The meta-analysis demonstrates that elevated ferritin levels are positive aassociated with metabolic syndrome. PMID:26550259

  5. Association between vitamin C intake and lung cancer: a dose-response meta-analysis

    PubMed Central

    Luo, Jie; Shen, Li; Zheng, Di

    2014-01-01

    Epidemiological studies evaluating the association between the intake of vitamin C and lung cancer risk have produced inconsistent results. We conducted a meta-analysis to assess the association between them. Pertinent studies were identified by a search of PubMed, Web of Knowledge and Wan Fang Med Online through December of 2013. Random-effect model was used to combine the data for analysis. Publication bias was estimated using Begg's funnel plot and Egger's regression asymmetry test. Eighteen articles reporting 21 studies involving 8938 lung cancer cases were included in this meta-analysis. Pooled results suggested that highest vitamin C intake level versus lowest level was significantly associated with the risk of lung cancer [summary relative risk (RR) = 0.829, 95%CI = 0.734–0.937, I2 = 57.8%], especially in the United States and in prospective studies. A linear dose-response relationship was found, with the risk of lung cancer decreasing by 7% for every 100 mg/day increase in the intake of vitamin C [summary RR = 0.93, 95%CI = 0.88–0.98]. No publication bias was found. Our analysis suggested that the higher intake of vitamin C might have a protective effect against lung cancer, especially in the United States, although this conclusion needs to be confirmed. PMID:25145261

  6. Meta-analysis of global metabolomic data identifies metabolites associated with life-span extension.

    PubMed

    Patti, Gary J; Tautenhahn, Ralf; Johannsen, Darcy; Kalisiak, Ewa; Ravussin, Eric; Brüning, Jens C; Dillin, Andrew; Siuzdak, Gary

    2014-08-01

    The manipulation of distinct signaling pathways and transcription factors has been shown to influence life span in a cell-non-autonomous manner in multicellular model organisms such as Caenorhabditis elegans. These data suggest that coordination of whole-organism aging involves endocrine signaling, however, the molecular identities of such signals have not yet been determined and their potential relevance in humans is unknown. Here we describe a novel metabolomic approach to identify molecules directly associated with extended life span in C. elegans that represent candidate compounds for age-related endocrine signals. To identify metabolic perturbations directly linked to longevity, we developed metabolomic software for meta-analysis that enabled intelligent comparisons of multiple different mutants. Simple pairwise comparisons of long-lived glp-1, daf-2, and isp-1 mutants to their respective controls resulted in more than 11,000 dysregulated metabolite features of statistical significance. By using meta-analysis, we were able to reduce this number to six compounds most likely to be associated with life-span extension. Mass spectrometry-based imaging studies suggested that these metabolites might be localized to C. elegans muscle. We extended the metabolomic analysis to humans by comparing quadricep muscle tissue from young and old individuals and found that two of the same compounds associated with longevity in worms were also altered in human muscle with age. These findings provide candidate compounds that may serve as age-related endocrine signals and implicate muscle as a potential tissue regulating their levels in humans.

  7. 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

  8. 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

  9. Meta-analysis of long-term mobile phone use and the association with brain tumours.

    PubMed

    Hardell, Lennart; Carlberg, Michael; Söderqvist, Fredrik; Hansson Mild, Kjell

    2008-05-01

    We evaluated long-term use of mobile phones and the risk for brain tumours in case-control studies published so far on this issue. We identified ten studies on glioma and meta-analysis yielded OR = 0.9, 95% CI = 0.8-1.1. Latency period of > or =10-years gave OR = 1.2, 95% CI = 0.8-1.9 based on six studies, for ipsilateral use (same side as tumour) OR = 2.0, 95% CI = 1.2-3.4 (four studies), but contralateral use did not increase the risk significantly, OR = 1.1, 95% CI = 0.6-2.0. Meta-analysis of nine studies on acoustic neuroma gave OR = 0.9, 95% CI = 0.7-1.1 increasing to OR = 1.3, 95% CI = 0.6-2.8 using > or =10-years latency period (four studies). Ipsilateral use gave OR = 2.4, 95% CI = 1.1-5.3 and contra-lateral OR = 1.2, 95% CI = 0.7-2.2 in the > or =10-years latency period group (three studies). Seven studies gave results for meningioma yielding overall OR = 0.8, 95% CI = 0.7-0.99. Using > or =10-years latency period OR = 1.3, 95% CI = 0.9-1.8 was calculated (four studies) increasing to OR = 1.7, 95% CI = 0.99-3.1 for ipsilateral use and OR = 1.0, 95% CI = 0.3-3.1 for contralateral use (two studies). We conclude that this meta-analysis gave a consistent pattern of an association between mobile phone use and ipsilateral glioma and acoustic neuroma using > or =10-years latency period.

  10. 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

    2016-04-30

    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.

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

    PubMed

    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 I (2) 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; I (2) = 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.

  12. Association of miR-21 with esophageal cancer prognosis: a meta-analysis.

    PubMed

    Wen, S-W; Zhang, Y-F; Li, Y; Liu, Z-X; Lv, H-L; Li, Z-H; Xu, Y-Z; Zhu, Y-G; Tian, Z-Q

    2015-06-12

    The present study aimed to explore the relationship between miRNA expression and survival in patients with esophageal cancer (EC) using meta-analysis. We searched PubMed, EMBASE, CNKI, Wanfang, and ISI Web of Science databases without time restrictions, and extracted relevant data, such as the name of first author, publication year, age, gender, number of case, etc. from the studies included. We calculated the pooled hazard ratios (HRs) using the RevMan 5.2 software. A total of five studies involving 504 subjects were included in the meta-analysis, with the purpose of analyzing the association of miRNA-21 expression with EC prognosis. The pooled HR of elevated versus decreased miR-21 expression in EC was 1.87 [95% confidence interval (CI): 1.37-2.55, P < 0.001], with elevated miR-21 expression being associated with poorer prognosis for patients with EC. Our results support a prognostic role for miR-21 in EC.

  13. Association between cholesterol intake and pancreatic cancer risk: evidence from a meta-analysis.

    PubMed

    Chen, Hongqiang; Qin, Shiyong; Wang, Minghai; Zhang, Tao; Zhang, Shuguang

    2015-02-04

    Quantification of the association between the intake of cholesterol and risk of pancreatic cancer is still conflicting. We therefore conducted a meta-analysis to summarize the evidence from epidemiological studies of cholesterol intake and the risk of pancreatic cancer. Pertinent studies were delivered by PubMed and Web of Knowledge issued through April of 2014. A random effects model was used to process the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationship was assessed by restricted cubic spline and variance-weighted least squares regression analysis. With 4513 pancreatic cases exemplified, 16 articles were applied in the meta-analysis. Pooled results suggest that cholesterol intake level was significantly associated with the risk of pancreatic cancer [summary relative risk (RR) = 1.371, 95%CI = 1.155-1.627, I(2) = 58.2%], especially in America [summary RR = 1.302, 95%CI = 1.090-1.556]. A linear dose-response relation was attested that the risk of pancreatic cancer rises by 8% with 100 mg/day of cholesterol intake. [summary RR = 1.08, 95% CI = 1.04-1.13]. In conclusion, our analysis suggests that a high intake of cholesterol might increase the risk of pancreatic cancer, especially in America.

  14. Association between neutrophil-to-lymphocyte ratio and differentiated thyroid cancer: a meta-analysis

    PubMed Central

    Liu, Ji-Feng; Ba, Luo; Lv, Hong; Lv, Dan; Du, Jin-Tao; Jing, Xiao-Mei; Yang, Ning-Jing; Wang, Shao-Xin; Li, Chao; Li, Xiao-Xia

    2016-01-01

    The association between neutrophil-to-lymphocyte ratio (NLR) and differentiated thyroid cancer (DTC) is undecided. To rectify this question, we conducted a systematic meta-analysis based on 7 prospective cohort studies published between 2013 and 2015, comprising 7349 patients. Six of these cohorts included pretreatment (baseline) NLR data for patients with thyroid nodules. The meta-analysis of these 6 cohorts showed that the NLR of patients with DTC (4617 cases) was statistically similar to patients with benign nodules only (1666 cases), with a mean difference (MD) of 0.19 (95% CI: −0.09 to 0.46; I2 = 93%; P < 0.001). No significant difference in NLR was found between patients with DTC and patients with benign nodules. Two studies addressed an association between NLR and papillary thyroid carcinoma in patients stratified by age <45 and ≥45 years (496 and 891 cases, respectively); the pooled MD was 0.09 (95% CI: −0.37 to 0.55; I2 = 92.2%, P < 0.001). An elevated NLR seems not a reliable indicator of progressing DTC in patients with goiters, and there was no difference in NLR between patients aged <45 years and those aged ≥45 years. Well-designed and large-scale investigations are warranted to understand the value of NLR in the prognosis of DTC. PMID:27941815

  15. Acute Tc-99m DMSA scan for identifying dilating vesicoureteral reflux in children: a meta-analysis.

    PubMed

    Mantadakis, Elpis; Vouloumanou, Evridiki K; Georgantzi, Georgia G; Tsalkidis, Aggelos; Chatzimichael, Athanassios; Falagas, Matthew E

    2011-07-01

    Controversy exists regarding the type and/or sequence of imaging studies needed during the first febrile urinary tract infection (UTI) in young children. Several investigators have claimed that because acute-phase Tc-99m dimercaptosuccinic acid (DMSA) renal-scan results are abnormal in the presence of dilating vesicoureteral reflux, a normal DMSA-scan result makes voiding cystourethrography (VCUG) unnecessary in the primary examination of infants with UTI. To evaluate the accuracy of acute-phase DMSA scanning in identifying dilating (grades III through V) vesicoureteral reflux documented by VCUG in children with a first febrile UTI, we performed a meta-analysis of the accuracy of diagnostic tests as reported from relevant studies identified through the PubMed and Scopus databases. Patient-based and renal unit-based analyses were performed. Overall, 13 cohort studies were identified. Nine studies involved patients younger than 2 years, 3 involved children aged 16 years or younger, and 1 involved exclusively neonates. Girls constituted 22% to 85% of the involved children. Pooled (95% confidence intervals) sensitivity and specificity rates of DMSA scanning were 79% and 53%, respectively, for the patient-based analysis (8 studies) and 60% and 65% for the renal unit-based analysis (5 studies). The respective areas under the hierarchical summary receiver operating curves were 0.71 and 0.67. Marked statistical heterogeneity was observed in both analyses, as indicated by I(2) test values of 91% and 87%, respectively. Acute-phase DMSA renal scanning cannot be recommended as replacement for VCUG in the evaluation of young children with a first febrile UTI.

  16. Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis.

    PubMed

    Bao, Ji-Ming; Song, Xian-Lu; Hong, Ying-Qia; Zhu, Hai-Li; Li, Cui; Zhang, Tao; Chen, Wei; Zhao, Shan-Chao; Chen, Qing

    2014-01-01

    Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR = 1.36, 95% CI = 1.10-1.69, P= 0.005; OR = 1.20, 95% CI = 1.04-1.37, P= 0.01; OR = 1.27, 95% CI = 1.10-1.46, P= 0.001; OR = 1.14, 95% CI = 1.01-1.27 and OR = 1.24, 95% CI = 1.07-1.43, P= 0.003, respectively). Analysis stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR = 1.54, 95% CI = 1.33-1.79, P < 0.001; OR = 1.38, 95% CI = 1.15-1.66, P= 0.001; and OR = 1.39, 95% CI = 1.15-1.67, P= 0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a significant association of five FOXO3A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

  17. A Meta-Analysis of Serological Response Associated with Yellow Fever Vaccination

    PubMed Central

    Jean, Kévin; Donnelly, Christl A.; Ferguson, Neil M.; Garske, Tini

    2016-01-01

    Despite previous evidence of high level of efficacy, no synthetic metric of yellow fever (YF) vaccine efficacy is currently available. Based on the studies identified in a recent systematic review, we conducted a random-effects meta-analysis of the serological response associated with YF vaccination. Eleven studies conducted between 1965 and 2011 representing 4,868 individual observations were included in the meta-analysis. The pooled estimate of serological response was 97.5% (95% confidence interval [CI] = 82.9–99.7%). There was evidence of between-study heterogeneity (I2 = 89.1%), but this heterogeneity did not appear to be related to study size, study design, or seroconversion measurement or definition. Pooled estimates were significantly higher (P < 0.0001) among studies conducted in nonendemic settings (98.9%, 95% CI = 98.2–99.4%) than among those conducted in endemic settings (94.2%, 95% CI = 83.8–98.1%). These results provide background information against which to evaluate the efficacy of fractional doses of YF vaccine that may be used in outbreak situations. PMID:27928091

  18. Association of IL10 Polymorphisms and Leprosy: A Meta-Analysis.

    PubMed

    Alvarado-Arnez, Lucia Elena; Amaral, Evaldo P; Sales-Marques, Carolinne; Durães, Sandra M B; Cardoso, Cynthia C; Nunes Sarno, Euzenir; Pacheco, Antonio G; Lana, Francisco C F; Moraes, Milton Ozório

    2015-01-01

    Leprosy is a chronic infectious disease that depends on the interplay of several factors. Single nucleotide polymorphisms (SNPs) in host immune related genes have been consistently suggested as participants in susceptibility towards disease. Interleukin-10 (IL-10) is a crucial immunomodulatory cytokine in mycobacterial pathogenesis and especially the -819C>T SNP (rs1800871) has been tested in several case-control studies indicating association with leprosy risk, although a recent consensus estimate is still missing. In this study, we evaluated the association of the -819C>T SNP and leprosy in two new Brazilian family-based populations. Then, we performed meta-analysis for this polymorphism summarizing published studies including these Brazilian family-based groups. Finally, we also retrieved published studies for other distal and proximal IL10 polymorphisms: -3575 T>A (rs1800890), -2849 G>A (rs6703630), -2763 C>A (rs6693899), -1082 G>A (rs1800896) and -592 C>A (rs1800872). Results from meta-analysis supported a significant susceptibility association for the -819T allele, with pooled Odds Ratio of 1.22 (CI = 1.11-1.34) and P-value = 3x10(-5) confirming previous data. This result remained unaltered after inclusion of the Brazilian family-based groups (OR = 1.2, CI = 1.10-1.31, P-value = 2x10(-5)). Also, meta-analysis confirmed association of -592 A allele and leprosy outcome (OR = 1.24, CI = 1.03-1.50, P-value = 0.02). In support of this, linkage disequilibrium analysis in 1000 genomes AFR, EUR, ASN and AMR populations pointed to r(2) = 1.0 between the -592C>A and -819C>T SNPs. We found no evidence of association for the other IL10 polymorphisms analyzed for leprosy outcome. Our results reinforce the role of the -819C>T as a tag SNP (rs1800871) and its association with leprosy susceptibility.

  19. Association between Helicobacter pylori infection and angiographically demonstrated coronary artery disease: A meta-analysis

    PubMed Central

    Yu, Xin-Juan; Yang, Xuan; Feng, Lei; Wang, Li-Li; Dong, Quan-Jiang

    2017-01-01

    Coronary artery disease (CAD) is a leading cause of mortality globally. However, the etiology and pathogenesis of CAD are not fully understood. The aim of the present meta-analysis was to estimate the association between the risk of CAD and Helicobacter pylori (H. pylori) infection. A literature search was performed to identify eligible studies published prior to August 14, 2014. Fixed or random effect meta-analytical methods were used to pool the data and perform the subgroup analyses. The effect measures estimated were the odds ratios (OR) for dichotomous data reported with 95% confidence intervals (95% CI). Of the 109 studies identified using the search parameters, 26 cross-sectional studies were eligible involving 3,901 CAD patients and 2,751 controls. H. pylori infection was associated with an increased risk of CAD (OR: 1.96, 95% CI: 1.47–2.63, P<0.00001). When the adjusted ORs were used to conduct another meta-analysis, the OR value decreased, but the association remained significant (OR: 1.42, 95% CI: 1.09–1.86, P=0.008). The association between H. pylori infection and CAD risk was stronger in younger individuals than in older individuals (OR: 2.36, 95% CI 1.50–3.73 vs. OR: 1.59, 95% CI: 1.19–2.11). A significant association was observed in studies from Europe (OR: 2.11, 95% CI: 1.54–2.88, P=0.01) and the USA (OR: 1.43, 95% CI: 1.08–1.91, P=0.36). There is a potential association between H. pylori infection and the risk of CAD. The association may be influenced by age and ethnicity.

  20. 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

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

    PubMed

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

    2017-01-21

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

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

    PubMed Central

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

    2017-01-01

    We performed expression studies to identify tissue non-specific genes and pathways of diabetes by meta-analysis. We searched curated datasets of the Gene Expression Omnibus (GEO) database and identified 13 and five expression studies of diabetes and insulin responses at various tissues, respectively. We tested differential gene expression by empirical Bayes-based linear method and investigated gene set expression association by knowledge-based enrichment analysis. Meta-analysis by different methods was applied to identify tissue non-specific genes and gene sets. We also proposed pathway mapping analysis to infer functions of the identified gene sets, and correlation and independent analysis to evaluate expression association profile of genes and gene sets between studies and tissues. Our analysis showed that PGRMC1 and HADH genes were significant over diabetes studies, while IRS1 and MPST genes were significant over insulin response studies, and joint analysis showed that HADH and MPST genes were significant over all combined data sets. The pathway analysis identified six significant gene sets over all studies. The KEGG pathway mapping indicated that the significant gene sets are related to diabetes pathogenesis. The results also presented that 12.8% and 59.0% pairwise studies had significantly correlated expression association for genes and gene sets, respectively; moreover, 12.8% pairwise studies had independent expression association for genes, but no studies were observed significantly different for expression association of gene sets. Our analysis indicated that there are both tissue specific and non-specific genes and pathways associated with diabetes pathogenesis. Compared to the gene expression, pathway association tends to be tissue non-specific, and a common pathway influencing diabetes development is activated through different genes at different tissues. PMID:28117714

  3. Association between the MDR1 gene variant C3435T and risk of leukaemia: a meta-analysis.

    PubMed

    Zhang, B-B; Xuan, C; Deng, K-F; Wu, N; Lun, L-M

    2013-09-01

    Although a number of genetic studies have attempted to link the multidrug resistance (MDR1) C3435T polymorphism to risk of leukaemia, the results were often inconsistent. The present study aimed at investigating the pooled association using a meta-analysis on the published studies. 1933 cases and 2215 controls of 11 published studies in English before June 2012 were involved in the updated meta-analysis. Furthermore, subgroup analysis was performed in different ethnic and leukaemia subtype groups. This meta-analysis suggests that the MDR1 C3435T polymorphism associate with risk of leukaemia. The effect of the variant on the expression levels and the possible functional role of the variant in leukaemia should be addressed in further studies.

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

    PubMed

    Baurecht, Hansjörg; Hotze, Melanie; Rodríguez, Elke; Manz, Judith; Weidinger, Stephan; Cordell, Heather J; Augustin, Thomas; Strauch, Konstantin

    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.

  5. Association between SERPING1 rs2511989 polymorphism and age-related macular degeneration: Meta-analysis

    PubMed Central

    Dong, Yi; Li, Ze-Dong; Fang, Xin-Yu; Shi, Xue-Feng; Chen, Song; Tang, Xin

    2015-01-01

    AIM To investigate the association between SERPING1 rs2511989 (G>A) polymorphism and age-related macular degeneration (AMD). METHODS A number of electronic databases (up to July 15, 2014) were searched independently by two investigators. A Meta-analysis was performed on the association between SERPING1 rs2511989 polymorphism and AMD. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. RESULTS Eight studies with 16 cohorts consisting of 9163 cases and 6813 controls were included in this Meta-analysis. There was no significant association between rs2511989 polymorphism and AMD under all genetic models in overall estimates (A vs G: OR= 0.938, 95%CI =0.858-1.025; AA vs GG:OR =0.871, 95%CI =0.719-1.056; AG vs GG: OR =0.944, 95%CI =0.845-1.054; AA+AG vs GG: OR =0.927, 95% CI =0.823-1.044; AA vs AG+GG: OR =0.890, 95%CI =0.780-1.034). Cumulative Meta-analyses also showed a trend of no association between rs2511989 polymorphism and AMD as information accumulated by year. Subgroup analysis and Meta-regression analysis indicated that age-matching status was the main source of heterogeneity. Sensitivity analysis found the results in overall comparisons and subgroup comparisons of white subjects under the allele model were found to have significantly statistical differences after studies deviating from Hardy-Weinberg equilibrium (HWE) were excluded (overall: OR=0.918, 95%CI = 0.844-0.999, P =0.049; whites: OR =0.901, 95%CI = 0.817-0.994, P =0.038). However, the results were not sufficiently robust for further sensitivity analysis and statistical differences disappeared on applying Bonferroni correction (with a significance level set at 0.05/25). CONCLUSION This Meta-analysis indicates that SERPING1 rs2511989 polymorphism and AMD tend to have no association with each other. Age matching status is a big confounding factor, and more studies with subtle designs are warranted in future. PMID:25938061

  6. Associations between sedentary behaviour and physical activity in children and adolescents: a meta-analysis.

    PubMed

    Pearson, N; Braithwaite, R E; Biddle, S J H; van Sluijs, E M F; Atkin, A J

    2014-08-01

    Physical activity and sedentary behaviour are associated with metabolic and mental health during childhood and adolescence. Understanding the inter-relationships between these behaviours will help to inform intervention design. This systematic review and meta-analysis synthesized evidence from observational studies describing the association between sedentary behaviour and physical activity in young people (<18 years). English-language publications up to August 2013 were located through electronic and manual searches. Included studies presented statistical associations between at least one measure of sedentary behaviour and one measure of physical activity. One hundred sixty-three papers were included in the meta-analysis, from which data on 254 independent samples was extracted. In the summary meta-analytic model (k = 230), a small, but significant, negative association between sedentary behaviour and physical activity was observed (r = -0.108, 95% confidence interval [CI] = -0.128, -0.087). In moderator analyses, studies that recruited smaller samples (n < 100, r = -0.193, 95% CI = -0.276, -0.109) employed objective methods of measurement (objectively measured physical activity; r = -0.233, 95% CI = -0.330, -0.137) or were assessed to be of higher methodological quality (r = -0.176, 95% CI = -0.215, -0.138) reported stronger associations, although effect sizes remained small. The association between sedentary behaviour and physical activity in young people is negative, but small, suggesting that these behaviours do not directly displace one another.

  7. Association of Thrombomodulin Gene Polymorphisms with Susceptibility to Atherosclerotic Diseases: A Meta-Analysis.

    PubMed

    Xu, Jie; Jin, Jun; Tan, Sheng

    2016-05-01

    Previous studies have proved that the dysfunction of thrombomodulin (TM) plays an important role in the pathogenesis of atherosclerotic diseases. In order to reveal their inherent relationship, we conducted a meta-analysis to uncover the association between two polymorphisms -33G/A and Ala455Val (c.1418C>T) in the TM gene and atherosclerotic diseases. We carried out a systematic search in PubMed, Science Direct, BIOSIS Previews, SpringerLink, the Cochrane library, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Database, the Wei Pu database, and the Wanfang Database. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were computed to show the association. We included 22 eligible studies which involved 5472 patients and 7786 controls. There were statistically significant associations between -33G/A polymorphisms in TM and the MI group under the Allele and Recessive models in Asians (G vs. A: OR = 0.67, 95%CI = 0.56-0.78, P < 0.00001; GG vs. GA+AA: OR = 0.66, 95%CI = 0.56-0.78, P < 0.00001). However, these findings of the overall and subgroups showed that Ala455Val polymorphisms did not have any relationship with atherosclerotic diseases. After Bonferroni correction, the above associations remained statistically significant. This meta-analysis provides robust evidence of association between the -33G/A polymorphism in the TM gene and the risk of myocardial infarction in Asians. The A allele may increase the incidence of MI in Asians. However, the Ala455Val variant was not associated with atherosclerotic risk. Further studies with adequate sample size are needed to verify our findings.

  8. Association between promoter methylation of DAPK gene and HNSCC: A meta-analysis

    PubMed Central

    Cai, Fucheng; Xiao, Xiyue; Niu, Xun; Zhong, Yi

    2017-01-01

    Background The death-associated protein kinase (DAPK) is a tumor suppressor gene, which is a mediator of cell death of INF-γ–induced apoptosis. Aberrant methylation of DAPK promoter has been reported in patients with head and neck squamous cell carcinoma (HNSCC). However, the results of these studies are inconsistent. Hence, the present study aimed to evaluate the association between the promoter methylation of DAPK gene and HNSCC. Methods Relevant studies were systematically searched in PubMed, Web of Science, Ovid, and Embase. The association between DAPK promoter methylation and HNSCC was assessed by odds ratio (ORs) and 95% confidence intervals (CI). To evaluate the potential sources of heterogeneity, we conducted the meta-regression analysis and subgroup analysis. Results Eighteen studies were finally included in the meta-analysis. The frequency of DAPK promoter methylation in patients with HNSCC was 4.09-fold higher than the non-cancerous controls (OR = 3.96, 95%CI = 2.26–6.95). A significant association between DAPK promoter methylation and HNSCC was found among the Asian region and the Non-Asia region (Asian region, OR = 4.43, 95% CI = 2.29–8.58; Non-Asia region, OR = 3.39, 95% CI = 1.18–9.78). In the control source, the significant association between DAPK promoter methylation and HNSCC was seen among the autologous group and the heterogeneous group (autologous group, OR = 2.71, 95% CI = 1.49–4.93; heterogeneous group, OR = 9.50, 95% CI = 2.98–30.27). DAPK promoter methylation was significantly correlated with alcohol status (OR = 1.85, 95% CI = 1.07–3.21). Conclusion The results of this meta-analysis suggested that aberrant methylation of DAPK promoter was associated with HNSCC. PMID:28249042

  9. 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

  10. 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

  11. Colorectal cancer association with metabolic syndrome and its components: a systematic review with meta-analysis.

    PubMed

    Esposito, Katherine; Chiodini, Paolo; Capuano, Annalisa; Bellastella, Giuseppe; Maiorino, Maria Ida; Rafaniello, Concetta; Panagiotakos, Demosthenes B; Giugliano, Dario

    2013-12-01

    We performed a systematic review and meta-analysis of the empirical evidence on the association of metabolic syndrome and its components with colorectal cancer incidence and mortality. A systematic literature search of multiple electronic databases was conducted and complemented by cross-referencing to identify studies published before 31 October 2012. Every included study was to report risk estimates with 95 % confidence intervals for the association between metabolic syndrome and colorectal cancer (incidence or mortality). Core items of identified studies were independently extracted by two reviewers, and results were summarized by standard methods of meta-analysis. We identified 17 studies, which reported on 49 data sets with 11,462 cancer cases. Metabolic syndrome was associated with an increased risk of colorectal cancer incidence and mortality in both men (RR: 1.33, 95 % CI 1.18-1.50, and 1.36, 1.25-1.48, respectively) and women (RR: 1.41, 1.18-1.70, and 1.16, 1.03-1.30, respectively). The risk estimates changed little depending on type of study (cohort vs non cohort), populations (US, Europe, Asia), cancer site (colon and rectum), or definition of the syndrome. The risk estimates for any single factor of the syndrome were significant for higher values of BMI/waist (RR: 1.19, 95 % CI 1.10-1.28), dysglycemia (RR: 1.29, 1.11-1.49), and higher blood pressure (RR: 1.09, 1.01-1.18). Dysglycemia and/or higher BMI/waist explained most of the risk associated with metabolic syndrome. Metabolic syndrome is associated with an increased risk of colorectal cancer incidence and mortality in both sexes. The risk conveyed by the full syndrome is not superior to the sum of its parts.

  12. 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

  13. Association between Dairy Intake and Gastric Cancer: A Meta-Analysis of Observational Studies

    PubMed Central

    Tian, Shu-bo; Yu, Jian-chun; Kang, Wei-ming; Ma, Zhi-qiang; Ye, Xin; Cao, Zhan-jiang

    2014-01-01

    Purpose Observational studies have given inconsistent findings on the relationship between intake of dairy products and gastric cancer. We therefore conducted a systematic review with a meta-analysis of observational studies to summarize available evidence on this point. Methods We searched the electronic literature databases of PubMed (Medline), EMBASE and the Chinese Biomedical Literature Database up until August 30, 2013. All studies were limited to the English language. Random-effects models were used to pool study results between dairy products consumption and the risk of gastric cancer. We also performed subgroup, publication bias and sensitivity analysis. Results Eight prospective studies and 18 case-control studies were included in our analysis, with a total number of 7272 gastric cancer cases and 223,355 controls. Pooled relative risks of all studies showed no significant association between dairy intake and gastric cancer (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 0.96–1.25). When study design was separately analyzed, population-based case-control studies showed a positive association between dairy intake and gastric cancer risk (OR: 1.36; 95% CI: 1.07–1.74), whereas no associations were shown by hospital-based case-control studies (OR: 0.86, 95% CI: 0.72–1.02) or cohort studies (OR = 1.01, 95% CI = 0.91–1.13). Conclusions The meta-analysis shows that no clear association apparently exists between consumption of dairy products and gastric cancer risk. Further well-designed cohort and intervention studies should be conducted to verify this lack of association. PMID:25006674

  14. 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

  15. Meta-analysis of the association between APC promoter methylation and colorectal cancer

    PubMed Central

    Ding, Zhenyu; Jiang, Tong; Piao, Ying; Han, Tao; Han, Yaling; Xie, Xiaodong

    2015-01-01

    Previous studies investigating the association between adenomatous polyposis coli (APC) gene promoter methylation and colorectal cancer (CRC) have yielded conflicting results. The aim of this study was to comprehensively evaluate the potential application of the detection of APC promoter methylation to the prevention and treatment of CRC. PubMed, Embase, and MEDLINE (results updated to October 2014) were searched for relevant studies. The effect size was defined as the weighted odds ratio (OR), which was calculated using either the fixed-effects or random-effects model. Prespecified subgroup and sensitivity analyses were conducted to evaluate potential heterogeneity among the included studies. Nineteen studies comprising 2,426 participants were selected for our meta-analysis. The pooled results of nine studies comprising a total of 740 subjects indicated that APC promoter methylation was significantly associated with CRC risk (pooled OR 5.53; 95% confidence interval [CI] 3.50–8.76; P<0.01). Eleven studies with a total of 1,219 patients evaluated the association between APC promoter methylation and the presence of CRC metastasis, and the pooled OR was 0.80 (95% CI 0.44–1.46; P=0.47). A meta-analysis conducted with four studies with a total of 467 patients found no significant correlation between APC promoter methylation and the presence of colorectal adenoma (pooled OR 1.85; 95% CI 0.67–5.10; P=0.23). No significant correlation between APC promoter methylation and patients’ Dukes’ stage, TNM stage, differentiation grade, age, or sex was identified. In conclusion, APC promoter methylation was found to be significantly associated with a higher risk of developing CRC. The findings indicate that APC promoter methylation may be a potential biomarker for the carcinogenesis of CRC. PMID:25632237

  16. Left ventricular hypertrophy in association with cognitive impairment: a systematic review and meta-analysis.

    PubMed

    Georgakis, Marios K; Synetos, Andreas; Mihas, Constantinos; Karalexi, Maria A; Tousoulis, Dimitrios; Seshadri, Sudha; Petridou, Eleni Th

    2017-02-16

    Left ventricular hypertrophy (LVH) is a marker of prolonged exposure to high blood pressure and a predictor of cardiovascular disease risk. The objective of the current study was to investigate its association with cognitive function. Following standard guidelines, pairs of independent reviewers screened 2359 articles to search for studies that addressed the research question, extracted data and evaluated the quality of the studies using the Newcastle-Ottawa scale; authors were contacted for additional data. A random-effects meta-analysis and a meta-regression analysis were performed. Eighteen eligible studies using various methodologies and of varying quality were identified. However, both cross-sectional and prospective studies were indicative of a positive association between LVH and cognitive impairment or cognitive performance and decline in both population-based and patient-based subjects. The meta-analysis showed an increased risk of cognitive impairment among subjects with LVH in population-based studies (9 studies; 28 648 subjects; odds ratio (OR): 1.40, 95% confidence interval (CI): 1.18-1.66) and studies exclusively on hypertensive subjects (3 studies; 1262 subjects; OR: 2.14, 95% CI: 1.39-3.30). The effect was stronger when assessing LVH by echocardiography rather than electrocardiogram and was retained in the sensitivity analyses of prospective and highest quality studies and studies adjusting for hypertension or blood pressure levels. No heterogeneity or publication bias was documented, whereas the presence of hypertension seemed to reinforce the reported association, as derived from the meta-regression analysis. There is evidence suggesting an independent association of LVH with cognitive impairment. Because of the highly heterogeneous methodologies, future large prospective studies with clinically defined dementia outcomes are needed to replicate the findings.Hypertension Research advance online publication, 16 February 2017; doi:10.1038/hr.2017.11.

  17. Association of smoking status with prognosis in bladder cancer: A meta-analysis

    PubMed Central

    Dai, Meng; Chen, Pengliang; Zhao, Hongfan; Wei, Qiang; Li, Fei; Tan, Wanlong

    2017-01-01

    There is considerable controversy regarding the association between smoking and prognosis in surgically treated bladder cancer. The present meta-analysis was performed to quantify the role of smoking status in bladder cancer recurrence, progression and patient survival by pooling the available previous data. Pubmed, Embase and the Cochrane Library databases were searched for eligible studies published prior to April 2016. Random and fixed effects models were used to calculate the summary relative risk estimates (SRRE). A total of 10,192 patients from 15 studies were included in the meta-analysis. There was evidence of positive associations between current smoking and the risk of recurrence (SRRE=1.23; 95% CI, 1.05–1.45) and mortality (SRRE=1.28; 95% CI, 1.07-1.52) in bladder cancer. Furthermore, former smoking had positive associations with bladder cancer recurrence (SRRE=1.22; 95% CI, 1.09-1.37) and mortality (SRRE=1.20; 95% CI, 1.03-1.41). However, there was no significant association between bladder cancer progression risk and current (SRRE=1.11; 95% CI, 0.71-1.75) or previous smoking (SRRE=1.16; 95% CI, 0.92-1.46). The findings indicate that current and former smoking increase the risk of recurrence and mortality in patients with bladder cancer. However, due to the nonrandomized and retrospective nature of the current study, patients may be prone to potential selection bias. Prospective and larger epidemiological studies with a longer follow-up are required to confirm these findings. PMID:27902481

  18. Association between Gout and Erectile Dysfunction: A Systematic Review and Meta-Analysis

    PubMed Central

    Song, Wen; Zhou, Xiang; Lv, Zheng-tao

    2016-01-01

    Background The aim of this systematic review and meta-analysis was to assess the possible association between gout and erectile dysfunction (ED). Methods Studies were identified by extensively searching EMBASE, Pubmed, CENTRAL and ISI Web of Science. Four electronic databases were searched from their inception date to the latest issue (March 2016), without language restriction. Each reviewer screened articles independently and was blinded to the findings of the other reviewer. Data was extracted in adherence to the predetermined data collection form and meta-analysis was conducted via RevMan 5.3. Results Five studies involving 56465 patients (mean age: 49.11 years) with gout and 155636 non-gout subjects (mean age: 48.76 years) were selected. The combination of unadjusted odds ratio (OR) showed that patients with gout were 1.44 times more likely to be diagnosed with ED when compared with control (95% confidence interval (95%CI) 1.20, 1.72). After adjustment for age and comorbidities, the heightened risk to develop ED was still present (1.18, 95%CI 1.02, 1.38). Subgroup-analysis by age showed statistically significant association of gout and ED in all age groups. However, evidence supporting a causal effect of gout on ED was insufficient. Conclusion The findings of this review indicated a positive association of gout and ED, but this work is hampered by the heterogeneity among included studies, to some extent. Future studies with larger community-based homogeneous population and randomized controlled trials aimed to evaluate the effect of gout treatment on ED associated outcomes are needed at this point. PMID:28036397

  19. Meta-analysis of the association between APC promoter methylation and colorectal cancer.

    PubMed

    Ding, Zhenyu; Jiang, Tong; Piao, Ying; Han, Tao; Han, Yaling; Xie, Xiaodong

    2015-01-01

    Previous studies investigating the association between adenomatous polyposis coli (APC) gene promoter methylation and colorectal cancer (CRC) have yielded conflicting results. The aim of this study was to comprehensively evaluate the potential application of the detection of APC promoter methylation to the prevention and treatment of CRC. PubMed, Embase, and MEDLINE (results updated to October 2014) were searched for relevant studies. The effect size was defined as the weighted odds ratio (OR), which was calculated using either the fixed-effects or random-effects model. Prespecified subgroup and sensitivity analyses were conducted to evaluate potential heterogeneity among the included studies. Nineteen studies comprising 2,426 participants were selected for our meta-analysis. The pooled results of nine studies comprising a total of 740 subjects indicated that APC promoter methylation was significantly associated with CRC risk (pooled OR 5.53; 95% confidence interval [CI] 3.50-8.76; P<0.01). Eleven studies with a total of 1,219 patients evaluated the association between APC promoter methylation and the presence of CRC metastasis, and the pooled OR was 0.80 (95% CI 0.44-1.46; P=0.47). A meta-analysis conducted with four studies with a total of 467 patients found no significant correlation between APC promoter methylation and the presence of colorectal adenoma (pooled OR 1.85; 95% CI 0.67-5.10; P=0.23). No significant correlation between APC promoter methylation and patients' Dukes' stage, TNM stage, differentiation grade, age, or sex was identified. In conclusion, APC promoter methylation was found to be significantly associated with a higher risk of developing CRC. The findings indicate that APC promoter methylation may be a potential biomarker for the carcinogenesis of CRC.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Meta-analysis of the association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese.

    PubMed

    Jin, Bin; Dong, Pin; Li, Keyong; Shen, Bin; Xie, Jin

    2014-01-01

    Glutathione S-transferase T1 (GSTT1) null genotype has been proven to be associated with risks of many cancers. There were also many studies assessing on the association between GSTT1 null genotype and nasopharyngeal carcinoma risk in Chinese, but the findings from those studies were inconsistent. We performed a meta-analysis to provide a more precise assessment on the effect of GSTT1 null genotype on nasopharyngeal carcinoma risk. The PubMed and Wanfang databases were searched to identify eligible case-control studies on the association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese. The pooled odds ratios (OR) with corresponding 95% confidence intervals (95% CI) were used to assess the association. Eight case-control studies with a total of 3,702 individuals were finally included in the meta-analysis. Meta-analysis of a total of eight studies showed that GSTT1 null genotype was significantly associated with increased risk of nasopharyngeal carcinoma in Chinese (OR = 2.27; 95% CI 1.41-3.67; P = 0.001). The finding from cumulative meta-analysis showed that there was a trend of more obvious association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese as data accumulated by publication year. Therefore, the GSTT1 null genotype is significantly associated with increased risk of nasopharyngeal carcinoma in Chinese.

  7. 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

  8. Meta-analysis of genome-wide association studies of anxiety disorders

    PubMed Central

    Otowa, Takeshi; Hek, Karin; Lee, Minyoung; Byrne, Enda M.; Mirza, Saira S.; Nivard, Michel G.; Bigdeli, Timothy; Aggen, Steven H.; Adkins, Daniel; Wolen, Aaron; Fanous, Ayman; Keller, Matthew C.; Castelao, Enrique; Kutalik, Zoltan; Van der Auwera, Sandra; Homuth, Georg; Nauck, Matthias; Teumer, Alexander; Milaneschi, Yuri; Hottenga, Jouke-Jan; Direk, Nese; Hofman, Albert; Uitterlinden, Andre; Mulder, Cornelis L.; Henders, Anjali K.; Medland, Sarah E.; Gordon, Scott; Heath, Andrew C.; Madden, Pamela A.F.; Pergadia, Michelle; van der Most, Peter J.; Nolte, Ilja M.; van Oort, Floor V.A.; Hartman, Catharina A.; Oldehinkel, Albertine J.; Preisig, Martin; Grabe, Hans Jörgen; Middeldorp, Christel M.; Penninx, Brenda WJH; Boomsma, Dorret; Martin, Nicholas G.; Montgomery, Grant; Maher, Brion S.; van den Oord, Edwin J.; Wray, Naomi R.; Tiemeier, Henning; Hettema, John M.

    2015-01-01

    Anxiety disorders, namely generalized anxiety disorder, panic disorder, and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based upon clinical presentation, anxiety disorders likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based anxiety disorders, we applied two phenotypic approaches: (1) comparisons between categorical anxiety disorder cases and super-normal controls, and (2) quantitative phenotypic factor scores derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65×10−8); for factor scores, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86×10−9). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of anxiety disorders. PMID:26754954

  9. Association of Adiponectin Gene (ADIPOQ) rs2241766 Polymorphism with Obesity in Adults: A Meta-Analysis

    PubMed Central

    Wu, Jingjing; Liu, Zheng; Meng, Kai; Zhang, Ling

    2014-01-01

    Background Adiponectin plays an important role in regulating glucose levels and fatty acid oxidation. Multiple studies have assessed the association between rs2241766 polymorphism in the adiponectin (ADIPOQ) gene and obesity susceptibility. However, the results are inconsistent and inconclusive. The aim of this meta-analysis was to investigate this association in adults. Method Several electronic databases were searched for relevant literature published up to November 2013. Statistical analyses were performed using software Review Manager (Version 5.02) and STATA (Version 10.0). The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a random-effects model or a fixed-effect model depending on heterogeneity among studies. Q tests and Egger’s tests were performed to assess heterogeneity and publication bias. Sensitivity analysis was conducted to confirm the reliability and stability of the meta-analysis. Results A total of 2,819 obese and 3,024 controls in 18 case-control studies were included in the meta-analysis. The results indicated that compared with TT genotype, the ADIPOQ-rs2241766 GG genotype was associated with an increased risk for obesity (OR = 1.39, 95% CI: 1.11–1.73, P for heterogeneity = 0.520, I2 = 0%) in overall studies. Whereas, GT genotype was associated with a borderland increased risk for obesity (OR = 1.13, 95% CI: 0.94–1.36, P for heterogeneity = 0.006, I2 = 51%). The susceptibility of obesity was increased based on genotypes of TT

  10. Evaluation of a Two-Stage Approach in Trans-Ethnic Meta-Analysis in Genome-Wide Association Studies.

    PubMed

    Hong, Jaeyoung; Lunetta, Kathryn L; Cupples, L Adrienne; Dupuis, Josée; Liu, Ching-Ti

    2016-05-01

    Meta-analysis of genome-wide association studies (GWAS) has achieved great success in detecting loci underlying human diseases. Incorporating GWAS results from diverse ethnic populations for meta-analysis, however, remains challenging because of the possible heterogeneity across studies. Conventional fixed-effects (FE) or random-effects (RE) methods may not be most suitable to aggregate multiethnic GWAS results because of violation of the homogeneous effect assumption across studies (FE) or low power to detect signals (RE). Three recently proposed methods, modified RE (RE-HE) model, binary-effects (BE) model and a Bayesian approach (Meta-analysis of Transethnic Association [MANTRA]), show increased power over FE and RE methods while incorporating heterogeneity of effects when meta-analyzing trans-ethnic GWAS results. We propose a two-stage approach to account for heterogeneity in trans-ethnic meta-analysis in which we clustered studies with cohort-specific ancestry information prior to meta-analysis. We compare this to a no-prior-clustering (crude) approach, evaluating type I error and power of these two strategies, in an extensive simulation study to investigate whether the two-stage approach offers any improvements over the crude approach. We find that the two-stage approach and the crude approach for all five methods (FE, RE, RE-HE, BE, MANTRA) provide well-controlled type I error. However, the two-stage approach shows increased power for BE and RE-HE, and similar power for MANTRA and FE compared to their corresponding crude approach, especially when there is heterogeneity across the multiethnic GWAS results. These results suggest that prior clustering in the two-stage approach can be an effective and efficient intermediate step in meta-analysis to account for the multiethnic heterogeneity.

  11. 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

  12. Association between serum Fe levels and obesity: a meta-analysis.

    PubMed

    Yang, Lijuan; Chen, Yi; Lu, Mi; Liu, Lei; Shi, Liuxia

    2015-06-01

    The purpose of this study is to clarify the association between serum Fe levels and Obesity using a meta-analysis approach. We searched eligible papers on the relevance published between 2006 and 2014 from the PubMed and the Chinese National Knowledge Infrastructure. Review Manage software was used to collect and analysis the date cited in the papers.6 eligible articles with 934 subjects from 40 case-control studies were identified. Overall,polled analysis indicated that subjects with obesity had lower Fe levels than healthy controls [standardized mean difference (SMD) = -0.738,95%confidence interval (CI) = (-1.228,-0.247)]. Thus, dietary supplement of Fe is recommended to prevent obesity.

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

    PubMed

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

    2017-02-23

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

  14. 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

  15. 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

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

    PubMed Central

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

    2017-01-01

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

  17. Association between serum level of magnesium and postmenopausal osteoporosis: a meta-analysis.

    PubMed

    Zheng, Jianmao; Mao, Xueli; Ling, Junqi; He, Qun; Quan, Jingjing; Jiang, Hongbo

    2014-06-01

    There are conflicting reports as to the association between serum level of magnesium (Mg) and postmenopausal osteoporosis (OP). The purpose of the present study is to clarify the association between serum level of Mg and postmenopausal OP using a meta-analysis approach. We searched articles indexed in Pubmed and the Chinese Journal Full-text Database (CJFD) published as of October 2013 that met our predefined criteria. Seven eligible studies involving 1,349 postmenopausal women from 12 case-control study arms were identified. Overall, pooled analysis indicated that postmenopausal osteoporotic women had a lower serum level of Mg than the healthy controls (standardized mean difference [SMD]=-0.55, 95 % confidence interval [CI]=-0.83 to -0.26). Further subgroup analysis found a similar pattern in Turkey (SMD=-0.66, 95% CI=-0.99 to -0.32) and Belgium (SMD=-0.98, 95% CI=-1.91 to -0.05), but not in China (SMD=0.02, 95% CI=-0.21 to 0.26). And the difference of serum level of Mg between postmenopausal osteoporotic women and healthy controls below the age of 60 years (SMD=-0.61, 95% CI=-1.09 to -0.13) was similar to that among the population over 60 years (SMD=-0.49, 95% CI=-0.80 to -0.18).In conclusion, this meta-analysis suggests that the low serum level of Mg seems to be a risk factor for OP among the postmenopausal women. 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 study to obtain better understanding of causal relationships between serum Mg and postmenopausal OP.

  18. Anxiety Disorders are Associated with Reduced Heart Rate Variability: A Meta-Analysis

    PubMed Central

    Chalmers, John A.; Quintana, Daniel S.; Abbott, Maree J.-Anne; Kemp, Andrew H.

    2014-01-01

    Background: Anxiety disorders increase risk of future cardiovascular disease (CVD) and mortality, even after controlling for confounds including smoking, lifestyle, and socioeconomic status, and irrespective of a history of medical disorders. While impaired vagal function, indicated by reductions in heart rate variability (HRV), may be one mechanism linking anxiety disorders to CVD, prior studies have reported inconsistent findings highlighting the need for meta-analysis. Method: Studies comparing resting-state HRV recordings in patients with an anxiety disorder as a primary diagnosis and healthy controls were considered for meta-analysis. Results: Meta-analyses were based on 36 articles, including 2086 patients with an anxiety disorder and 2294 controls. Overall, anxiety disorders were characterized by lower HRV [high frequency (HF): Hedges’ g = −0.29. 95% CI: −0.41 to −0.17, p < 0.001; time domain: Hedges’ g = −0.45, 95% CI: −0.57 to −0.33, p < 0.001] than controls. Panic disorder (n = 447), post-traumatic stress disorder (n = 192), generalized anxiety disorder (n = 68), and social anxiety disorder (n = 90), but not obsessive–compulsive disorder (n = 40), displayed reductions in HF HRV relative to controls (all ps < 0.001). Conclusion: Anxiety disorders are associated with reduced HRV, findings associated with a small-to-moderate effect size. Findings have important implications for future physical health and well-being of patients, highlighting a need for comprehensive cardiovascular risk reduction. PMID:25071612

  19. 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.

  20. 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

  1. The Association between VDR Gene Polymorphisms and Diabetic Retinopathy Susceptibility: A Systematic Review and Meta-Analysis

    PubMed Central

    Xia, Wei; Lu, Ping

    2016-01-01

    Aims. Studies on the associations of vitamin D receptor (VDR) gene polymorphisms with diabetic retinopathy (DR) susceptibility reported conflicting results. A systematic meta-analysis was undertaken to clarify this topic. Methods. A systematic search of electronic databases (PubMed, EMBASE, and CNKI) was carried out until March 31, 2016. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association. Results. A total of 7 studies fulfilling the inclusion criteria were included in this meta-analysis (649 cases and 707 controls). Pooled ORs showed a significant association between FokI polymorphism and DR risk in all the four genetic models (OR = 1.612 (1.354~1.921), 1.988 (1.481~2.668), 1.889 (1.424~2.505), and 2.674 (1.493~4.790) in allelic, dominant, recessive, and additive models, resp., PZ < 0.01), but not for TaqI or BsmI polymorphism (PZ > 0.05). Similar results were found in the subgroup analysis. Sensitivity analysis indicated that the results were relatively stable and reliable. Results of Begg's and Egger's tests suggested a lack of publication bias. Conclusions. Our meta-analysis demonstrated that DR was significantly associated with VDR gene FokI polymorphism. However, due to the relatively small sample size in this meta-analysis, further studies with a larger sample size should be done to confirm the findings. PMID:27891515

  2. Associations of Parenting Styles and Dimensions with Academic Achievement in Children and Adolescents: A Meta-Analysis

    ERIC Educational Resources Information Center

    Pinquart, Martin

    2016-01-01

    Parents and researchers alike are interested in how to promote children's academic competence. The present meta-analysis integrates the results of 308 empirical studies on associations of general parenting dimensions and styles with academic achievement of children and adolescents assessed via grade point average or academic achievement tests.…

  3. Airborne asbestos exposures associated with gasket and packing replacement: a simulation study and meta-analysis.

    PubMed

    Madl, Amy K; Hollins, Dana M; Devlin, Kathryn D; Donovan, Ellen P; Dopart, Pamela J; Scott, Paul K; Perez, Angela L

    2014-08-01

    Exposures to airborne asbestos during the removal and installation of internal gaskets and packing associated with a valve overhaul were characterized and compared to published data according to different variables (e.g., product, equipment, task, tool, setting, duration). Personal breathing zone and area samples were collected during twelve events simulating gasket and packing replacement, clean-up and clothing handling. These samples were analyzed using PCM and TEM methods and PCM-equivalent (PCME) airborne asbestos concentrations were calculated. A meta-analysis was performed to compare these data with airborne asbestos concentrations measured in other studies involving gaskets and packing. Short-term mechanic and assistant airborne asbestos concentrations during valve work averaged 0.013f/cc and 0.008f/cc (PCME), respectively. Area samples averaged 0.008f/cc, 0.005f/cc, and 0.003f/cc (PCME) for center, bystander, and remote background, respectively. Assuming a tradesman conservatively performs 1-3 gasket and/or packing replacements daily, an average 8-h TWA was estimated to be 0.002-0.010f/cc (PCME). Combining these results in a meta-analysis of the published exposure data showed that the majority of airborne asbestos exposures during work with gaskets and packing fall within a consistent and low range. Significant differences in airborne concentrations were observed between power versus manual tools and removal versus installation tasks. Airborne asbestos concentrations resulting from gasket and packing work during a valve overhaul are consistent with historical exposure data on replacement of asbestos-containing gasket and packing materials involving multiple variables and, in nearly all plausible scenarios, result in average airborne asbestos concentrations below contemporaneous occupational exposure limits for asbestos.

  4. Meta-Analysis of the Association between Vitiligo and Human Leukocyte Antigen-A

    PubMed Central

    Ren, Jianwen; Niu, Xinwu; Xu, Qingqiang; Wang, Xiaopeng; Liu, Yale

    2016-01-01

    Objective. The objective of this study was to systematically evaluate the association between vitiligo and human leukocyte antigen- (HLA-) A. Methods. PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, and reference lists were searched for relevant original articles. Results. Nineteen case-control studies comprising 3042 patients and 5614 controls were included, in which 33 HLA-A alleles were reported. Overall, three alleles (HLA-A⁎02, A⁎33, and Aw⁎31) were significantly associated with increased risk of vitiligo, two (HLA-A⁎09 and Aw⁎19) were associated with decreased risk, and the remaining 28 were unassociated. Twelve alleles, seven alleles, and 19 alleles were common to three ethnicities, both types of vitiligo, and both typing methods, respectively. In the subgroup analysis by ethnicity and typing methods, the association of six alleles and five alleles was inconsistent in three populations and both typing methods, respectively. In the subgroup analysis by clinical type, the association of all seven alleles was consistent in both types of vitiligo. Conclusion. The meta-analysis suggests that HLA-A⁎02, A⁎33, and Aw⁎31 are associated with increased risk of vitiligo, while HLA-A⁎09 and Aw⁎19 are associated with decreased risk of vitiligo. The association of some alleles varies in terms of ethnicity and typing methods. PMID:27689083

  5. Factors Associated with Poststroke Anxiety: A Systematic Review and Meta-Analysis.

    PubMed

    Wright, Francesca; Wu, Simiao; Chun, Ho-Yan Yvonne; Mead, Gillian

    2017-01-01

    Background and Purpose. Anxiety affects 25% of stroke survivors. There are no effective treatments. Poststroke depression, prestroke anxiety and depression, locus of control, coping, confidence, fatigue, and sleep are factors that may be associated with poststroke anxiety and can potentially be targeted by therapy. We systematically reviewed the literature and performed a meta-analysis to identify associations with these factors. Methods. We searched electronic databases from January 2014 to July 2015 to complement a literature search performed from inception to May 2014. Study quality was assessed using an internationally endorsed checklist. We used odds ratios (ORs) to estimate the strength of associations and random-effects modelling to calculate summary effect sizes. Results. There were 24 studies recruiting 15448 patients. Quality of reporting was satisfactory. 13 studies with 2408 patients reported associations between poststroke anxiety and poststroke depression (OR = 4.66, 95% confidence interval: 2.23, 9.74). One study reported association with prestroke anxiety, three with prestroke depression, one with fatigue, and two with sleep. No studies reported on locus of control, coping, or confidence. Conclusion. Poststroke anxiety was associated with depression but there are limited data on other modifiable associations. Further research is needed to identify potential targets for treatment.

  6. Factors Associated with Poststroke Anxiety: A Systematic Review and Meta-Analysis

    PubMed Central

    Wu, Simiao

    2017-01-01

    Background and Purpose. Anxiety affects 25% of stroke survivors. There are no effective treatments. Poststroke depression, prestroke anxiety and depression, locus of control, coping, confidence, fatigue, and sleep are factors that may be associated with poststroke anxiety and can potentially be targeted by therapy. We systematically reviewed the literature and performed a meta-analysis to identify associations with these factors. Methods. We searched electronic databases from January 2014 to July 2015 to complement a literature search performed from inception to May 2014. Study quality was assessed using an internationally endorsed checklist. We used odds ratios (ORs) to estimate the strength of associations and random-effects modelling to calculate summary effect sizes. Results. There were 24 studies recruiting 15448 patients. Quality of reporting was satisfactory. 13 studies with 2408 patients reported associations between poststroke anxiety and poststroke depression (OR = 4.66, 95% confidence interval: 2.23, 9.74). One study reported association with prestroke anxiety, three with prestroke depression, one with fatigue, and two with sleep. No studies reported on locus of control, coping, or confidence. Conclusion. Poststroke anxiety was associated with depression but there are limited data on other modifiable associations. Further research is needed to identify potential targets for treatment. PMID:28321357

  7. The Association Between Apolipoprotein E and Functional Outcome After Traumatic Brain Injury: A Meta-Analysis.

    PubMed

    Li, Lizhuo; Bao, Yijun; He, Songbai; Wang, Gang; Guan, Yanlei; Ma, Dexuan; Wu, Rile; Wang, Pengfei; Huang, Xiaolong; Tao, Shanwei; Liu, Qiwen; Wang, Yunjie; Yang, Jingyun

    2015-11-01

    Traumatic brain injury (TBI) is a leading cause of death and disability. Previous studies have investigated the association of apolipoprotein E (APOE) ε4 with functional outcome after TBI and reported inconsistent results.The purpose of this study was to perform a systematic literature search and conduct meta-analyses to examine whether APOE ε4 is associated with poorer functional outcome in patients with TBI.We performed a systematic literature search in PubMed, Cochrane Library, Embase, Google Scholar, and HuGE.The eligibility criteria of this study included the following: Patients had TBI; the studies reported APOE genotype data or provided odds ratios (ORs) and the corresponding 95% confidence intervals (CIs); the functional outcome was assessed using the Glasgow Outcome Scale (GOS) or the Glasgow Outcome Scale Extended (GOSE); and patients were followed for at least 3 months after TBI.In all meta-analyses, we used random-effects models to calculate the odds ratio as a measure of association. We examined the association of APOE ε4 with functional outcome at different time points after TBI.A total of 12 studies met the eligibility criteria and were included in the meta-analyses. We did not find a significant association between APOE ε4 and functional outcome at 6 (P = 0.23), 12 (P = 0.44), and 24 months (P = 0.85) after TBI. However, APOE ε4 was associated with an increased risk of unfavorable long-term (≥6 months) functional outcome after TBI (OR = 1.36, 95% CI: 1.07-1.74, P = 0.01).Limitations of this study include The sample size was limited; the initial severity of TBI varied within and across studies; we could not control for potential confounding factors, such as age at injury and sex; a meta-analysis of the genotype dosage effect was not feasible; and we could not examine the association with specific factors such as neurobehavioral or specific cognitive functions.Our meta-analysis indicates APOE ε4 is associated with the long

  8. Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas

    PubMed Central

    Parra, E. J.; Below, J. E.; Krithika, S.; Valladares, A.; Barta, J. L.; Cox, N. J.; Hanis, C. L.; Wacher, N.; Garcia-Mena, J.; Hu, P.; Shriver, M. D.; Kumate, J.; McKeigue, P. M.; Escobedo, J.; Cruz, M.

    2013-01-01

    Aims/hypothesis We report a genome-wide association study of type 2 diabetes in an admixed sample from Mexico City and describe the results of a meta-analysis of this study and another genome-wide scan in a Mexican-American sample from Starr County, TX, USA. The top signals observed in this meta-analysis were followed up in the Diabetes Genetics Replication and Meta-analysis Consortium (DIAGRAM) and DIAGRAM+ datasets. Methods We analysed 967 cases and 343 normoglycaemic controls. The samples were genotyped with the Affymetrix Genome-wide Human SNP array 5.0. Associations of genotyped and imputed markers with type 2 diabetes were tested using a missing data likelihood score test. A fixed-effects meta-analysis including 1,804 cases and 780 normoglycaemic controls was carried out by weighting the effect estimates by their inverse variances. Results In the meta-analysis of the two Hispanic studies, markers showing suggestive associations (p<10−5) were identified in two known diabetes genes, HNF1A and KCNQ1, as well as in several additional regions. Meta-analysis of the two Hispanic studies and the recent DIAGRAM+ dataset identified genome-wide significant signals (p<5×10−8) within or near the genes HNF1A and CDKN2A/CDKN2B, as well as suggestive associations in three additional regions, IGF2BP2, KCNQ1 and the previously unreported C14orf70. Conclusions/interpretation We observed numerous regions with suggestive associations with type 2 diabetes. Some of these signals correspond to regions described in previous studies. However, many of these regions could not be replicated in the DIAGRAM datasets. It is critical to carry out additional studies in Hispanic and American Indian populations, which have a high prevalence of type 2 diabetes. PMID:21573907

  9. A genome-wide association meta-analysis on apolipoprotein A-IV concentrations.

    PubMed

    Lamina, Claudia; Friedel, Salome; Coassin, Stefan; Rueedi, Rico; Yousri, Noha A; Seppälä, Ilkka; Gieger, Christian; Schönherr, Sebastian; Forer, Lukas; Erhart, Gertraud; Kollerits, Barbara; Marques-Vidal, Pedro; Ried, Janina; Waeber, Gerard; Bergmann, Sven; Dähnhardt, Doreen; Stöckl, Andrea; Kiechl, Stefan; Raitakari, Olli T; Kähönen, Mika; Willeit, Johann; Kedenko, Ludmilla; Paulweber, Bernhard; Peters, Annette; Meitinger, Thomas; Strauch, Konstantin; Study Group, Kora; Lehtimäki, Terho; Hunt, Steven C; Vollenweider, Peter; Kronenberg, Florian

    2016-08-15

    Apolipoprotein A-IV (apoA-IV) is a major component of HDL and chylomicron particles and is involved in reverse cholesterol transport. It is an early marker of impaired renal function. We aimed to identify genetic loci associated with apoA-IV concentrations and to investigate relationships with known susceptibility loci for kidney function and lipids. A genome-wide association meta-analysis on apoA-IV concentrations was conducted in five population-based cohorts (n = 13,813) followed by two additional replication studies (n = 2,267) including approximately 10 M SNPs. Three independent SNPs from two genomic regions were significantly associated with apoA-IV concentrations: rs1729407 near APOA4 (P = 6.77 × 10 (-)  (44)), rs5104 in APOA4 (P = 1.79 × 10(-)(24)) and rs4241819 in KLKB1 (P = 5.6 × 10(-)(14)). Additionally, a look-up of the replicated SNPs in downloadable GWAS meta-analysis results was performed on kidney function (defined by eGFR), HDL-cholesterol and triglycerides. From these three SNPs mentioned above, only rs1729407 showed an association with HDL-cholesterol (P = 7.1 × 10 (-)  (07)). Moreover, weighted SNP-scores were built involving known susceptibility loci for the aforementioned traits (53, 70 and 38 SNPs, respectively) and were associated with apoA-IV concentrations. This analysis revealed a significant and an inverse association for kidney function with apoA-IV concentrations (P = 5.5 × 10(-)(05)). Furthermore, an increase of triglyceride-increasing alleles was found to decrease apoA-IV concentrations (P = 0.0078). In summary, we identified two independent SNPs located in or next the APOA4 gene and one SNP in KLKB1 The association of KLKB1 with apoA-IV suggests an involvement of apoA-IV in renal metabolism and/or an interaction within HDL particles. Analyses of SNP-scores indicate potential causal effects of kidney function and by lesser extent triglycerides on apoA-IV concentrations.

  10. A genome-wide association meta-analysis on apolipoprotein A-IV concentrations

    PubMed Central

    Lamina, Claudia; Friedel, Salome; Coassin, Stefan; Rueedi, Rico; Yousri, Noha A.; Seppälä, Ilkka; Gieger, Christian; Schönherr, Sebastian; Forer, Lukas; Erhart, Gertraud; Kollerits, Barbara; Marques-Vidal, Pedro; Ried, Janina; Waeber, Gerard; Bergmann, Sven; Dähnhardt, Doreen; Stöckl, Andrea; Kiechl, Stefan; Raitakari, Olli T.; Kähönen, Mika; Willeit, Johann; Kedenko, Ludmilla; Paulweber, Bernhard; Peters, Annette; Meitinger, Thomas; Strauch, Konstantin; Study Group, KORA; Lehtimäki, Terho; Hunt, Steven C.; Vollenweider, Peter; Kronenberg, Florian

    2016-01-01

    Apolipoprotein A-IV (apoA-IV) is a major component of HDL and chylomicron particles and is involved in reverse cholesterol transport. It is an early marker of impaired renal function. We aimed to identify genetic loci associated with apoA-IV concentrations and to investigate relationships with known susceptibility loci for kidney function and lipids. A genome-wide association meta-analysis on apoA-IV concentrations was conducted in five population-based cohorts (n = 13,813) followed by two additional replication studies (n = 2,267) including approximately 10 M SNPs. Three independent SNPs from two genomic regions were significantly associated with apoA-IV concentrations: rs1729407 near APOA4 (P = 6.77 × 10 − 44), rs5104 in APOA4 (P = 1.79 × 10−24) and rs4241819 in KLKB1 (P = 5.6 × 10−14). Additionally, a look-up of the replicated SNPs in downloadable GWAS meta-analysis results was performed on kidney function (defined by eGFR), HDL-cholesterol and triglycerides. From these three SNPs mentioned above, only rs1729407 showed an association with HDL-cholesterol (P = 7.1 × 10 − 07). Moreover, weighted SNP-scores were built involving known susceptibility loci for the aforementioned traits (53, 70 and 38 SNPs, respectively) and were associated with apoA-IV concentrations. This analysis revealed a significant and an inverse association for kidney function with apoA-IV concentrations (P = 5.5 × 10−05). Furthermore, an increase of triglyceride-increasing alleles was found to decrease apoA-IV concentrations (P = 0.0078). In summary, we identified two independent SNPs located in or next the APOA4 gene and one SNP in KLKB1. The association of KLKB1 with apoA-IV suggests an involvement of apoA-IV in renal metabolism and/or an interaction within HDL particles. Analyses of SNP-scores indicate potential causal effects of kidney function and by lesser extent triglycerides on apoA-IV concentrations. PMID

  11. 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

  12. 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.

  13. Are Shunt Revisions Associated with IQ in Congenital Hydrocephalus? A Meta -Analysis.

    PubMed

    Arrington, C Nikki; Ware, Ashley L; Ahmed, Yusra; Kulesz, Paulina A; Dennis, Maureen; Fletcher, Jack M

    2016-12-01

    Although it is generally acknowledged that shunt revisions are associated with reductions in cognitive functions in individuals with congenital hydrocephalus, the literature yields mixed results and is inconclusive. The current study used meta-analytic methods to empirically synthesize studies addressing the association of shunt revisions and IQ in individuals with congenital hydrocephalus. Six studies and three in-house datasets yielded 11 independent samples for meta-analysis. Groups representing lower and higher numbers of shunt revisions were coded to generate effect sizes for differences in IQ scores. Mean effect size across studies was statistically significant, but small (Hedges' g = 0.25, p < 0.001, 95 % CI [0.08, 0.43]) with more shunt revisions associated with lower IQ scores. Results show an association of lower IQ and more shunt revisions of about 3 IQ points, a small effect, but within the error of measurement associated with IQ tests. Although clinical significance of this effect is not clear, results suggest that repeated shunt revisions because of shunt failure is associated with a reduction in cognitive functions.

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

    PubMed Central

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

    2016-01-01

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

  15. 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

  16. Associations between XRCC1 Gene Polymorphisms and Coronary Artery Disease: A Meta-Analysis

    PubMed Central

    Ma, Wen-Qi; Han, Xi-Qiong; Wang, Xin; Wang, Ying; Zhu, Yi; Liu, Nai-Feng

    2016-01-01

    Genetic variations that influence DNA repair efficiency may contribute to coronary artery disease (CAD) susceptibility. Previous studies have investigated whether there was evidence of an association between polymorphisms at the X-ray repair cross complementing 1 (XRCC1) gene and susceptibility to CAD, but findings have been inconclusive. We identified eligible studies through a comprehensive literature search to determine whether an association exists between XRCC1 gene polymorphisms and CAD susceptibility. Findings were assessed using the odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed- or random-effects model, based on the heterogeneity of the studies. Ten eligible studies were finally included in this meta-analysis. Our pooled analysis found that XRCC1 polymorphisms were significantly associated with CAD susceptibility under recessive (Arg194Trp: OR = 1.47, 95% CI = 1.13–1.93; Arg399Gln: OR = 1.45, 95% CI = 1.12–1.89), homozygous (Arg194Trp: OR = 1.37, 95% CI = 1.03–1.81; Arg399Gln: OR = 1.56, 95% CI = 1.19–2.05), and allele (Arg399Gln: OR = 1.18, 95% CI = 1.06–1.32) genetic models. Following subgroup analysis by ethnicity, in Asian populations, we found evidence of associations between the XRCC1 Arg194Trp polymorphism and CAD under recessive and homozygous genetic models, and between the XRCC1 Arg399Gln polymorphism and CAD under recessive, homozygous, and allele genetic models. Subgroup analysis stratified by control source revealed associations between the Arg194Trp and Arg399Gln polymorphisms and susceptibility to CAD under recessive and homozygous modes of inheritance, respectively. In addition, subgroup analysis stratified by sample size found that findings of the Arg194Trp polymorphism in large sample sizes were comparable to those found using pooled eligible studies. Based on our meta-analysis, we concluded that the XRCC1 gene polymorphisms, Arg194Trp and Arg399Gln, are associated with CAD

  17. Association between allergies and multiple sclerosis: a systematic review and meta-analysis.

    PubMed

    Monteiro, L; Souza-Machado, A; Menezes, C; Melo, A

    2011-01-01

    Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that expresses a typical type 1 immune response (Th1). Allergies, on the other hand, present with high levels of type 2 (Th2) cytokines. Some authors observed that Th1 and Th2 diseases could coexist in the same subject. Besides its biological plausibility, the association between MS and allergies remains controversial. The aim of this systematic review and meta-analysis was to determine if there is an association between allergic diseases and MS. All clinical and epidemiological studies on patients with MS published up to July 2009, that assessed the association between allergic diseases and MS were reviewed. A total of 1010 articles were retrieved from search, and ten epidemiological studies were included in the analysis. The results showed that there is no evidence supporting an association between allergic diseases (OR: 0.91; CI 95%: 0.68-1.23), asthma (OR: 0.83; CI 95%: 0.48-1.44), allergic rhinitis (OR: 0.81; CI 95%: 0.59-1.12), eczema (OR: 0.93; CI 95%: 0.71-1.23) and MS. Additional prospective studies in this field might help to elucidate the nature of these associations.

  18. 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

  19. Metabolic syndrome is associated with increased breast cancer risk: a systematic review with meta-analysis.

    PubMed

    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 I (2) 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; I (2) = 69.55%). No publication bias was observed. Conclusions. MS is associated with increased breast cancer risk in adult women.

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

    PubMed

    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

    2014-06-15

    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.

  1. Association between bipolar spectrum disorder and bone health: a meta-analysis and systematic review protocol

    PubMed Central

    Brennan-Olsen, Sharon L; Stuart, Amanda L; Pasco, Julie A; Berk, Michael; Hodge, Jason M; Williams, Lana J

    2017-01-01

    Introduction Bipolar spectrum disorder is a chronic, episodic illness, associated with significant personal, social and economic burden. It is estimated to affect ∼2.4% of the population worldwide and is commonly associated with psychological and/or physiological comorbidities. Osteoporosis is one such comorbidity, a disease of bone that is asymptomatic until a fracture occurs. This systematic review attempts to capture, collate, assess and discuss the literature investigating the association between bipolar spectrum disorder and bone health. Methods and analysis We aim to identify articles that investigate the association between bipolar spectrum disorder and bone health in adults by systematically searching the MEDLINE, PubMed, OVID and CINAHL databases. Two independent reviewers will determine eligibility of studies according to predetermined criteria, and methodological quality will be assessed using a previously published scoring system. A meta-analysis will be conducted, and statistical methods will be used to identify and control for heterogeneity, if possible. If numerical syntheses are prevented due to statistical heterogeneity, a best evidence synthesis will be conducted to assess the level of evidence for associations between bipolar spectrum disorder and bone health. Ethics and dissemination Ethical permission will not be required for this systematic review since only published data will be used. This protocol will be registered with PROSPERO. Findings of the review will be published in a peer-reviewed scientific journal, and will be presented to clinical and population health audiences at national and international conferences. PMID:28246138

  2. 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

  3. 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

  4. 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

  5. Guidance for the utility of linear models in meta-analysis of genetic association studies of binary phenotypes.

    PubMed

    Cook, James P; Mahajan, Anubha; Morris, Andrew P

    2017-02-01

    Linear mixed models are increasingly used for the analysis of genome-wide association studies (GWAS) of binary phenotypes because they can efficiently and robustly account for population stratification and relatedness through inclusion of random effects for a genetic relationship matrix. However, the utility of linear (mixed) models in the context of meta-analysis of GWAS of binary phenotypes has not been previously explored. In this investigation, we present simulations to compare the performance of linear and logistic regression models under alternative weighting schemes in a fixed-effects meta-analysis framework, considering designs that incorporate variable case-control imbalance, confounding factors and population stratification. Our results demonstrate that linear models can be used for meta-analysis of GWAS of binary phenotypes, without loss of power, even in the presence of extreme case-control imbalance, provided that one of the following schemes is used: (i) effective sample size weighting of Z-scores or (ii) inverse-variance weighting of allelic effect sizes after conversion onto the log-odds scale. Our conclusions thus provide essential recommendations for the development of robust protocols for meta-analysis of binary phenotypes with linear models.

  6. Association between esophageal cancer risk and EPHX1 polymorphisms: A meta-analysis

    PubMed Central

    Li, Qin-Tao; Kang, Wei; Wang, Man; Yang, Jun; Zuo, Yang; Zhang, Wei; Su, Dan-Ke

    2014-01-01

    AIM: To summarize the relationship between p.Tyr113His and p.His139Arg polymorphisms in microsomal epoxide hydrolase (EPHX1) and risk for esophageal cancer (EC). METHODS: The MEDLINE/PubMed and EMBASE databases were searched for studies of the association between EPHX1 polymorphisms and EC risk that were published from the database inception date to April 2013. A total of seven case-control studies, including seven on p.Tyr113His (cases, n = 1118; controls, n = 1823) and six on p.His139Arg (cases, n = 861; controls, n = 1571), were included in the meta-analysis. After data extraction by two investigators working independently, the meta-analyses were carried out with STATA 11.0 software. Pooled odds ratios and 95%CI were calculated using a fixed-effects model or a random-effects model, as appropriate. RESULTS: The pooled EPHX1 p.Tyr113His polymorphism data showed no significant association with EC in any of the genetic models (OR = 1.00, 95%CI: 0.70-1.48 for Tyr/His vs Tyr/Tyr; OR = 1.10, 95%CI: 0.77-1.57 for His/His vs Tyr/Tyr; OR = 1.06, 95%CI: 0.75-1.49 for a dominant model; OR = 1.09, 95%CI: 0.89-1.34 for a recessive model). Similar results were obtained from the p.His139Arg polymorphism analysis (Arg/His vs His/His: OR = 1.02, 95%CI: 0.84-1.23; Arg/Arg vs His/His: OR = 0.96, 95%CI: 0.60-1.54; OR = 1.03, 95%CI: 0.78-1.37 for the dominant model; OR = 0.97, 95%CI: 0.61-1.56 for the recessive model). Subgroup analyses for ethnicity, subtype of EC, and source of controls (population-based or hospital-based) showed trends that were consistent with the pooled analysis (reported above), with no significant associations found. CONCLUSION: This meta-analysis suggests that the p.Tyr113His and p.His139Arg polymorphisms in EPHX1 may not be associated with EC development. PMID:24803829

  7. 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

  8. 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

  9. 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

  10. Association of the 5HTR2A gene with suicidal behavior: CASE-control study and updated meta-analysis

    PubMed Central

    2013-01-01

    Background The polymorphism rs6313 (T102C) has been associated with suicidal behavior in case–control and meta-analysis studies, but results and conclusions remain controversial. The aim of the present study was to examine the association between T102C with suicidal behavior in a case–control study and, to assess the combined evidence – this case–control study and available data from other related studies – we carried out a meta-analysis. Methods We conducted a case–control study that included 161 patients with suicide attempts and 244 controls; we then performed a meta-analysis. The following models were evaluated in the meta-analysis: A) C allele vs T allele; B) T allele vs C allele; C) Caucasian population, D) Asian population, and E) suicide attempters with schizophrenia. Results We found an association between attempted suicide and control participants for genotype (χ2=6.28, p=0.04, df=2) and allele (χ2=6.17, p=0.01, df=1, OR 1.48 95% IC: 1.08-2.03) frequencies in the case–control study. The meta-analysis, comprising 23 association studies (including the present one), showed that the rs6313 polymorphism is not associated with suicidal behavior for the following comparisons:T allele vs C allele (OR: 1.03; 95% CI 0.93-1.13; p(Z)=0.44); C allele vs T allele: (OR:0.99; 95% CI: 0.90-1.08; p(Z)=0.22); Caucasians (OR:1.09; 95% CI: 0.96-1.23), and Asians (OR:0.96; 95% CI: 0.84-1.09). Conclusion Our results showed association between the rs6313 (T102C) polymorphism and suicidal behavior in the case–control study. However, the meta-analysis showed no evidence of association. Therefore, more studies are necessary to determine conclusively an association between T102C and suicidal behavior. PMID:23311440

  11. 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

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

    PubMed

    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.

  13. CTLA-4 polymorphisms associate with breast cancer susceptibility in Asians: a meta-analysis

    PubMed Central

    Liu, Xinghan; Lin, Shuai; Yang, Pengtao; Liu, Kang; Zheng, Yi; Xu, Peng; Liu, Meng; Yang, Xuewen

    2017-01-01

    Previous studies have investigated the association between cytotoxic T-lymphocyte antigen-4 (CTLA-4) polymorphisms and breast cancer susceptibility, but the results remained inconsistent. Therefore, we evaluated the relationship between four common CTLA-4 polymorphisms and breast cancer risk by a meta-analysis, aiming to derive a comprehensive and precise conclusion. We searched EMBASE, Pubmed, Web of Science, CNKI, and Wanfang databases until July 18th, 2016. Finally, ten eligible studies involving 4,544 breast cancer patients and 4,515 cancer-free controls were included; all these studies were from Asia. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the breast cancer risk in five genetic models. The results indicated that the CTLA-4 +49A>G (rs231775) polymorphism had a significant association with decreased breast cancer risk in allelic, homozygous, dominant and recessive models. Also, the +6230G>A (rs3087243) polymorphism reduced breast cancer risk especially in the Chinese population under homozygous and recessive models. In contrast, the −1661A>G (rs4553808) polymorphism increased breast cancer risk in allelic, heterozygous and dominant models, whereas −1722 T>C (rs733618) did not relate to breast cancer risk. In conclusion, CTLA-4 polymorphisms significantly associate with breast cancer susceptibility in Asian populations, and different gene loci may have different effects on breast cancer development. Further large-scale studies including multi-racial populations are required to confirm our findings. PMID:28097051

  14. Association between MTR A2756G polymorphism and childhood acute lymphoblastic leukemia: a meta-analysis.

    PubMed

    Xia, Jia; Wang, Yadan; Zhang, Hang; Hu, Yu

    2014-06-01

    Abstract To date, many studies on the association between methionine synthase (MTR) A2756G and childhood acute lymphoblastic leukemia (ALL) have provided either controversial or inconclusive results. To clarify the effect of MTR A2756G on the risk of childhood acute lymphoblastic leukemia, a meta-analysis of all relevant studies was performed. The fixed effects model showed that the 2756A allele was associated with a decreased risk of childhood ALL compared with the G allele (ORA vs. G = 0.872; 95% CI 0.782-0.974; p = 0.015, I(2) = 46.9%). Additionally, when comparing subjects with ALL and controls with AA vs. AG or AA vs. AG + GG (dominant model), significant differences were found in the fixed effects model (ORAA vs. AG = 0.869; 95% CI 0.760-0.994; p = 0.040, I(2) = 26.4%; ORAA vs. AG+ GG = 0.858; 95% CI 0.754-0.976; p = 0.020, I(2) = 39.6%). In a subgroup analysis in a population with the same background, individuals with the AA genotype had a reduced risk of developing ALL compared to individuals with the AG genotype. In conclusion, our study provides evidence suggesting that MTR A2756G is associated with a reduced risk of developing childhood ALL.

  15. 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

  16. CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches.

    PubMed

    Werling, Anna Maria; Bobrowski, Elise; Taurines, Regina; Gundelfinger, Ronnie; Romanos, Marcel; Grünblatt, Edna; Walitza, Susanne

    2016-03-01

    The Contactin Associated Protein-like 2 (CNTNAP2) gene has been discussed to be associated with different symptoms of autism spectrum disorders (ASDs) and other neurodevelopmental disorders. We aimed to elucidate the genetic association of CNTNAP2 within high functioning ASD (HFA), focusing on autism specific symptoms and reducing intelligence related factors. Furthermore, we compared our findings conducting a meta-analysis in patients with ASD and HFA only. A case-control association study was performed for HFA (HFA, n = 105; controls, n = 133). Moreover, we performed a family-based association study (DFAM) analysis (HFA, n = 44; siblings, n = 57). Individuals were genotyped for the two most frequently reported single nucleotide polymorphisms (SNPs) in the CNTNAP2 gene (rs2710102, rs7794745). Furthermore, a meta-analysis using the MIX2 software integrated our results with previously published data. A significant association for the carriers of the T-allele of the rs7794745 with HFA was found in the case-control sample [OR = 1.547; (95 % CI 1.056-2.266); p = 0.025]. No association could be found by DFAM with any of the CNTNAP2 SNPs with HFA. The meta-analysis of both SNPs did not show a significant association with either ASD or with HFA. Overall, including case-control, sibs, and meta-analysis, we could not detect any significant association with the CNTNAP2 gene and HFA. Our results point in the direction that CNTNAP2 may not play a major role in HFA, but rather seems to have a significance in neurodevelopmental disorders or in individuals displaying intellectual delays.

  17. Association between Circulating Vitamin D Level and Urolithiasis: A Systematic Review and Meta-Analysis.

    PubMed

    Hu, Henglong; Zhang, Jiaqiao; Lu, Yuchao; Zhang, Zongbiao; Qin, Baolong; Gao, Hongbin; Wang, Yufeng; Zhu, Jianning; Wang, Qing; Zhu, Yunpeng; Xun, Yang; Wang, Shaogang

    2017-03-18

    Many studies compared the serum/plasma 1,25 dihydroxyvitamin D₃ (1,25(OH)₂D) and 25 hydroxyvitamin D₃ (25(OH)D) between people with and without nephrolithiasis, and their results were conflicting. After systematically searching PubMed, Web of Science, The Cochrane Library, CNKI, and the Wanfang Database, we conducted a meta-analysis. Thirty-two observational studies involving 23,228 participants were included. Meta-analysis of these studies showed that of stone formers (SFs), calcium SFs had significantly higher concentrations of 1,25(OH)₂D (weighted mean difference (WMD), 10.19 pg/mL; 95% confidence interval (CI), 4.31-16.07; p = 0.0007 and WMD, 11.28 pg/mL; 95% CI, 4.07-18.50; p = 0.002, respectively) than non-stone formers, while the levels of 25(OH)D (WMD, 0.88 ng/mL; 95% CI, -1.04-2.80; p = 0.37 and WMD, -0.63 ng/mL; 95% CI, -2.72-1.47; p = 0.56, respectively) are similar. Compared with controls and normocalciuria SFs, hypercalciuria SFs had increased circulating 1,25(OH)₂D (WMD, 9.41 pg/mL; 95% CI, 0.15-18.67; p = 0.05 and WMD, 2.75 pg/mL; 95% CI, -0.20-5.69; p = 0.07, respectively) and markedly higher 25(OH)D (WMD, 5.02 ng/mL; 95% CI, 0.99-9.06; p = 0.01 and WMD, 5.02 ng/mL; 95% CI, 2.14-7.90; p = 0.0006, respectively). Normocalciuria SFs had elevated 1,25(OH)₂D level (WMD, 6.85 pg/mL; 95% CI, -5.00-18.71; p = 0.26) and comparable 25(OH)D (WMD, 0.94 ng/mL; 95% CI, -3.55-5.43; p = 0.68). Sensitivity analysis generated similar results. Current evidence suggests that increased circulating 1,25(OH)₂D is associated with urinary stones and a higher level of circulating 25(OH)D is significantly associated with hypercalciuria urolithiasis. Further studies are still needed to reconfirm and clarify the role of vitamin D in the pathogenesis of stones.

  18. Association between Circulating Vitamin D Level and Urolithiasis: A Systematic Review and Meta-Analysis

    PubMed Central

    Hu, Henglong; Zhang, Jiaqiao; Lu, Yuchao; Zhang, Zongbiao; Qin, Baolong; Gao, Hongbin; Wang, Yufeng; Zhu, Jianning; Wang, Qing; Zhu, Yunpeng; Xun, Yang; Wang, Shaogang

    2017-01-01

    Many studies compared the serum/plasma 1,25 dihydroxyvitamin D3 (1,25(OH)2D) and 25 hydroxyvitamin D3 (25(OH)D) between people with and without nephrolithiasis, and their results were conflicting. After systematically searching PubMed, Web of Science, The Cochrane Library, CNKI, and the Wanfang Database, we conducted a meta-analysis. Thirty-two observational studies involving 23,228 participants were included. Meta-analysis of these studies showed that of stone formers (SFs), calcium SFs had significantly higher concentrations of 1,25(OH)2D (weighted mean difference (WMD), 10.19 pg/mL; 95% confidence interval (CI), 4.31–16.07; p = 0.0007 and WMD, 11.28 pg/mL; 95% CI, 4.07–18.50; p = 0.002, respectively) than non-stone formers, while the levels of 25(OH)D (WMD, 0.88 ng/mL; 95% CI, −1.04–2.80; p = 0.37 and WMD, −0.63 ng/mL; 95% CI, −2.72–1.47; p = 0.56, respectively) are similar. Compared with controls and normocalciuria SFs, hypercalciuria SFs had increased circulating 1,25(OH)2D (WMD, 9.41 pg/mL; 95% CI, 0.15–18.67; p = 0.05 and WMD, 2.75 pg/mL; 95% CI, −0.20–5.69; p = 0.07, respectively) and markedly higher 25(OH)D (WMD, 5.02 ng/mL; 95% CI, 0.99–9.06; p = 0.01 and WMD, 5.02 ng/mL; 95% CI, 2.14–7.90; p = 0.0006, respectively). Normocalciuria SFs had elevated 1,25(OH)2D level (WMD, 6.85 pg/mL; 95% CI, −5.00–18.71; p = 0.26) and comparable 25(OH)D (WMD, 0.94 ng/mL; 95% CI, −3.55–5.43; p = 0.68). Sensitivity analysis generated similar results. Current evidence suggests that increased circulating 1,25(OH)2D is associated with urinary stones and a higher level of circulating 25(OH)D is significantly associated with hypercalciuria urolithiasis. Further studies are still needed to reconfirm and clarify the role of vitamin D in the pathogenesis of stones. PMID:28335477

  19. Association between glutathione S-transferase M1 null genotype and risk of gallbladder cancer: a meta-analysis.

    PubMed

    Sun, Hong-Li; Han, Bing; Zhai, Hong-Peng; Cheng, Xin-Hua; Ma, Kai

    2014-01-01

    Glutathione S-transferases (GSTs) are a family of enzymes which are involved in the detoxification of potential carcinogens. Glutathione S-transferase M1 (GSTM1) null genotype can impair the enzyme activity of GSTs and is suspected to increase the susceptibility to gallbladder cancer. Previous studies investigating the association between GSTM1 null genotype and risk of gallbladder cancer reported inconsistent findings. To quantify the association between GSTM1 null genotype and risk of gallbladder cancer, we performed a meta-analysis of published studies. We searched PubMed, Embase, and Wanfang databases for all possible studies. We estimated the pooled odds ratio (OR) with its 95% confidence interval (95% CI) to assess the association. Meta-analysis of total included studies showed that GSTM1 null genotype was not associated with gallbladder cancer risk (OR = 1.13, 95% CI 0.88-1.46, P = 0.332). Subgroup analysis by ethnicity showed that there was no association between GSTM1 null genotype and risk of gallbladder cancer in both Caucasians and Asians. However, meta-analysis of studies with adjusted estimations showed that GSTM1 null genotype was associated with increased risk of gallbladder cancer (OR = 1.46, 95% CI 1.02-2.09, P = 0.038). Thus, this meta-analysis shows that GSTM1 null genotype is likely to be associated with risk of gallbladder cancer. More studies with well design and large sample size are needed to further validate the association between GSTM1 null genotype and gallbladder cancer.

  20. Prevention of ventilator-associated pneumonia through aspiration of subglottic secretions: a systematic review and meta-analysis.

    PubMed

    Leasure, A Renee; Stirlen, Joan; Lu, Shu Hua

    2012-01-01

    Ventilator-associated pneumonia (VAP) is a subset of hospital-acquired pneumonias and is a serious, sometimes fatal, complication in patients who need mechanical ventilation. In addition, pay-for-performance initiative has placed increased emphasis on preventing nosocomial infections including VAP. Facilities may not be reimbursed for costs associated with prevalence infections. This article presents a review and meta-analysis of the prevention of VAP through the aspiration of subglottic secretion.

  1. GSTM1 Null Genotype and GSTP1 Ile105Val Polymorphism Are Associated with Alzheimer's Disease: a Meta-Analysis.

    PubMed

    Wang, Mo; Li, Yu; Lin, Lulu; Song, Guijun; Deng, Teng

    2016-03-01

    Published studies on the associations between glutathione S-transferase (GST) polymorphisms and Alzheimer's disease reported controversial findings. A meta-analysis of published studies was performed to assess the associations between polymorphisms of GSTM1, GSTT1 and GSTP1, and Alzheimer's disease. PubMed, Embase, and other databases were searched for case-control on the associations between polymorphisms of GSTM1, GSTT1 and GSTP1, and Alzheimer's disease. The odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the associations. Eleven articles were finally included into the meta-analysis, including eight studies on GSTM1 null genotype, six studies on GSTT1 null genotype, and six studies on GSTP1 Ile105Val polymorphism. Overall, GSTM1 null genotype was associated with increased risk of Alzheimer's disease (fixed effect OR = 1.34, 95% CI 1.10-1.64, P = 0.004). GSTT1 null genotype was not associated with risk of Alzheimer's disease (random effect OR = 1.15, 95% CI 0.68-1.92, P = 0.60). Besides, GSTP1 Ile105Val polymorphism was significantly associated with increased risk of Alzheimer's disease (Val vs Ile: OR = 1.45, 95% CI 1.05-1.99, P = 0.023; ValVal vs IleIle: OR = 1.87, 95% CI 1.30-2.69, P = 0.001; ValVal vs IleIle + IleVal: OR = 1.76, 95% CI 1.24-2.51, P = 0.002). No obvious risk of publication bias was observed in the meta-analysis. GSTM1 null genotype and GSTP1 Ile105Val polymorphism are associated with increased risk of Alzheimer's disease. More studies with large sample size are needed to validate the findings in the meta-analysis.

  2. FMRI signals associated with memory strength in the medial temporal lobes: a meta-analysis.

    PubMed

    Wais, Peter E

    2008-12-01

    To identify patterns of memory-related neural activity in the medial temporal lobes (MTL), a quantitative meta-analysis of 17 functional magnetic resonance imaging (fMRI) studies was performed. The analysis shows that increased activity in the hippocampus and the parahippocampal cortex predicts subsequent memory strength. During retrieval, activity in the hippocampus increases in association with strong memory. In the perirhinal cortex, increased activity predicts subsequent recognition, whether based on weak or strong memory, whereas during retrieval activity decreases below the level for misses in association with both weak and strong memory. The results are consistent with the claim that the hippocampus selectively subserves recollection, whereas adjacent structures subserve familiarity [Eichenbaum, H., Yonelinas, A., & Ranganath, C. (2007). The medial temporal lobe and recognition memory. The Annual Review of Neuroscience, 30, 123-152]. However, this conclusion depends on a specific dual-process theory of recognition memory that has been used to interpret the results. An alternative dual-process model holds that the behavioral methods used to differentiate recollection from familiarity instead separate strong memories from weak memories. When the fMRI data are interpreted in terms of the alternative theory, the fMRI results do not point to selective roles for the hippocampus or the adjacent MTL structures. The fMRI data alone cannot distinguish between these two models, so other methods are needed to resolve the issue.

  3. 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.

  4. 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

  5. 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

    2016-03-09

    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.

  6. 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

  7. Association between the methionine synthase A2756G polymorphism and neural tube defect risk: a meta-analysis.

    PubMed

    Yang, Mei; Yang, Liping; Qi, Ling; Guo, Yiyang; Lin, Xiaofang; Zhang, Yu; Du, Yukai

    2013-05-10

    Many studies have accessed the association between methionine synthase (MTR) A2756G polymorphism and neural tube defect (NTD). However, the conclusions are inconsistent. Our study aimed to clarify the nature of the genetic risks contributed by this polymorphism for NTD using meta-analysis. We searched electronic literature from the PubMed, EMBASE, and Medline databases, from which 10 articles were selected according to the inclusion criteria. The meta-analysis was conducted in 3 groups, namely, NTD patients, mothers with NTD offspring and fathers with NTD offspring. Pooled odds ratios (ORs) and 95% confidence intervals were used to evaluate the strength of the association and the result was corrected by multiple testing. To sum up, no associations between the MTR A2756G polymorphism and NTD risk were found among the 3 groups in all genetic models. However, as their sample size is not large enough, this result needs further research.

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

    PubMed

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

    2015-09-03

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

  9. Thiazolidinediones and associated risk of bladder cancer: a systematic review and meta-analysis

    PubMed Central

    Turner, Richard M; Kwok, Chun S; Chen-Turner, Chen; Maduakor, Chinedu A; Singh, Sonal; Loke, Yoon K

    2014-01-01

    Aims To determine whether thiazolidinedione use is associated with a risk of bladder cancer. Methods We searched MEDLINE and EMBASE in June 2012 (with PubMed update to July 2013) and conducted meta-analysis on the overall risks of bladder cancer with pioglitazone or rosiglitazone and the risk with different categories of cumulative dose or duration of drug use. Results We screened 230 citations and included 18 studies, comprising five randomized controlled trials (RCTs) and 13 observational studies. Meta-analysis showed a significantly higher overall risk of bladder cancer with pioglitazone in RCTs [7878 participants; odds ratio (OR) 2.51, 95% confidence interval (CI) 1.09–5.80] and observational studies (>2.6 million patients; OR for ‘ever’ users vs. non-users 1.21, 95% CI 1.09–1.35). Subgroup analysis of observational studies by cumulative dose showed the risk of bladder cancer to be greatest with >28.0 g of pioglitazone (OR 1.64, 95% CI 1.28–2.12). A significantly increased risk was found with both 12–24 months (OR 1.41, 95% CI 1.16–1.71) and >24 months (OR 1.51, 95% CI 1.26–1.81) cumulative durations of pioglitazone exposure. No significant risk was seen with rosiglitazone in RCTs (OR 0.84, 95% CI 0.35–2.04) or ‘ever’ users vs. non-users in observational studies (OR 1.03, 95% CI 0.94–1.12); the evidence for any relationship between bladder cancer risk and rosiglitazone cumulative duration is limited and inconsistent. Direct comparison of pioglitazone to rosiglitazone ‘ever’ users yielded an OR of 1.25 (95% CI 0.91–1.72). Conclusions A modest but clinically significant increase in the risk of bladder cancer with pioglitazone was found, which appears to be related to cumulative dose and duration of exposure. We recommend that prescribers limit pioglitazone use to shorter durations. PMID:24325197

  10. Association between cytochrome P450 1A1 MspI polymorphism and endometrial cancer risk: a meta-analysis.

    PubMed

    Han, Linxiao; Liu, Yanyan; Cao, Weiwei; Yuan, Xiuying; Li, Cuifeng

    2013-10-01

    Many studies proposed that cytochrome P450 1A1 (CYP1A1) MspI polymorphism may be associated with endometrial cancer risk, but the findings from previous studies reported conflicting results. A meta-analysis of all relevant studies was performed to get a comprehensive assessment of the association between CYP1A1 MspI polymorphism and endometrial cancer risk. Eligible studies were searched in PubMed and China National Knowledge Infrastructure databases. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to evaluate the association. Twelve studies with a total of 2,111 cases and 2,894 controls were finally included into the meta-analysis. Overall, meta-analysis of a total of 12 studies showed that there was no obvious association between CYP1A1 MspI polymorphism and endometrial cancer risk (ORC vs. T = 0.97, 95 % CI 0.77-1.22, P OR = 0.808; ORCC vs. TT = 1.00, 95 % CI 0.57-1.76, P OR = 0.994; ORCC vs. TT/TC = 0.88, 95 % CI 0.65-1.20, P OR = 0.425; ORCC/TC vs. TT = 0.98, 95 % CI 0.74-1.29, P OR = 0.861). Subgroup analyses by ethnicity further showed that there was no obvious association between CYP1A1 MspI polymorphism and endometrial cancer risk in both Caucasians and Asians. There was no obvious risk of publication bias. Therefore, the meta-analysis suggests that CYP1A1 MspI polymorphism is not associated with endometrial cancer risk.

  11. Traumatic brain injury is associated with subsequent neurologic and psychiatric disease: a meta-analysis

    PubMed Central

    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.

    2016-01-01

    Object Mild traumatic brain injury (TBI) has been proposed as a risk factor for 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 subsequent diagnosis (i.e., at least one year post-injury) of neurologic or psychiatric disease. Methods All studies from 1995–2012 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 design and characteristics. Results 57 studies met inclusion criteria. A random effects meta-analysis revealed a significant association of prior TBI with subsequent neurologic and psychiatric diagnosis. The pooled odds ratio (OR) for TBI on development of any illness was 1.67 (95% CI 1.44–1.93, p<.001). Prior TBI was independently associated with both neurologic [OR 1.55 (95% CI 1.31–1.83, p<.001)] and psychiatric [OR 2.00 (95% CI 1.50–2.66, p<.001)] outcomes. Analyses of individual diagnoses found higher odds of Alzheimer’s disease, Parkinson’s disease, mild cognitive impairment, depression, mixed affective disorders, and bipolar disorder in individuals with previous TBI 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 found 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 neurologic and psychiatric illness. This indicates that either TBI is a risk factor for heterogeneous pathologic processes or that TBI may contribute to a common pathologic mechanism. PMID:26315003

  12. A comprehensive meta-analysis of genetic associations between five key SNPs and colorectal cancer risk

    PubMed Central

    Li, Wei; Liu, Dahai; He, Kan

    2016-01-01

    Genome-wide association studies (GWAS) on colorectal cancer (CRC) have identified dozens of single nucleotide polymorphisms (SNPs) in more than 19 independent loci associated with CRC. Due to the heterogeneity of the studied subjects and the contrary results, it is challenging to verify the certainty of the association between these loci and CRC. We conducted a critical review of the published studies of SNPs associated with CRC. Five most frequently reported SNPs, which are rs6983267/8q24.21, rs4939827/18q21.1, rs10795668/10p14, rs4444235/14q22.2 and rs4779584/ 15q13.3, were selected for the current study from the qualified studies. Then meta-analyses based on larger sample sizes with average of 33,000 CRC cases and 34,000 controls were performed to assess the association between SNPs and CRC risk. Heterogeneity among studies and publication bias were assessed by the χ2-based Q statistic test Begg's funnel plot or Egger's test, respectively. Our meta-analysis confirmed significant associations of the five SNPs with CRC risk under different genetic models. Two risk variants at rs6983267 {Odds Ratio (OR) 1.388, 95% Confidence Interval (CI) 1.180-1.8633} and rs10795668 (OR 1.323, 95% CI 1.062-1.648) had the highest ORs in homogeneous model. While ORs of the other three variants at rs4939827 {OR 1.298, 95% CI 1.135-1.483}, rs4779584 (OR 1.261, 95% CI 1.146-1.386) and rs4444235 (OR 1.160, 95% CI 1.106-1.216) were also statistically significant. Sensitivity analyses and publication bias assessment indicated the robust stability and reliability of the results. PMID:27661122

  13. 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

  14. 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

  15. 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

  16. Meta-analysis of association of the matrix metalloproteinase 2 (-735 C/T) polymorphism with cancer risk.

    PubMed

    Kim, Su Kang; Kang, Sang Wook; Park, Hae Jeong; Ban, Ju Yeon; Oh, Chung-Hun; Chung, Joo-Ho; Oh, In-Hwan; Cho, Kyu Bong; Park, Min-Su

    2015-01-01

    The association between matrix metalloproteinase 2 (MMP2) gene polymorphisms and cancer risk has been investigated in many published studies; however, the currently available results are inconclusive. Therefore, we performed a meta-analysis to provide conclusive evidence for an association between the MMP2 polymorphism (-735 C/T) and cancer risk. Sixteen case-control studies with 11792 individuals were included in this meta-analysis. The odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Overall, the MMP2 polymorphism (-735 C/T) was not associated with cancer risk in any of the models. However, the subgroup analysis revealed that dominant model (C/T+T/T vs. C/C: OR=1.24, 95% CI=1.01-1.53) and codominant 1 model (C/T vs. C/C: OR=1.30, 95% CI=1.05-1.62) were significantly associated with cancer risk in the Caucasian population. In conclusion, our meta-analysis indicated that the MMP2 polymorphism (-735 C/T) might be genetic risk factor for the carcinogenesis in Caucasians. However, more studies with a larger sample size are needed to provide more precise evidence.

  17. 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.

  18. Meta-analysis and imputation refines the association of 15q25 with smoking quantity.

    PubMed

    Liu, Jason Z; Tozzi, Federica; Waterworth, Dawn M; Pillai, Sreekumar G; Muglia, Pierandrea; Middleton, Lefkos; Berrettini, Wade; Knouff, Christopher W; Yuan, Xin; Waeber, Gérard; Vollenweider, Peter; Preisig, Martin; Wareham, Nicholas J; Zhao, Jing Hua; Loos, Ruth J F; Barroso, Inês; Khaw, Kay-Tee; Grundy, Scott; Barter, Philip; Mahley, Robert; Kesaniemi, Antero; McPherson, Ruth; Vincent, John B; Strauss, John; Kennedy, James L; Farmer, Anne; McGuffin, Peter; Day, Richard; Matthews, Keith; Bakke, Per; Gulsvik, Amund; Lucae, Susanne; Ising, Marcus; Brueckl, Tanja; Horstmann, Sonja; Wichmann, H-Erich; Rawal, Rajesh; Dahmen, Norbert; Lamina, Claudia; Polasek, Ozren; Zgaga, Lina; Huffman, Jennifer; Campbell, Susan; Kooner, Jaspal; Chambers, John C; Burnett, Mary Susan; Devaney, Joseph M; Pichard, Augusto D; Kent, Kenneth M; Satler, Lowell; Lindsay, Joseph M; Waksman, Ron; Epstein, Stephen; Wilson, James F; Wild, Sarah H; Campbell, Harry; Vitart, Veronique; Reilly, Muredach P; Li, Mingyao; Qu, Liming; Wilensky, Robert; Matthai, William; Hakonarson, Hakon H; Rader, Daniel J; Franke, Andre; Wittig, Michael; Schäfer, Arne; Uda, Manuela; Terracciano, Antonio; Xiao, Xiangjun; Busonero, Fabio; Scheet, Paul; Schlessinger, David; St Clair, David; Rujescu, Dan; Abecasis, Gonçalo R; Grabe, Hans Jörgen; Teumer, Alexander; Völzke, Henry; Petersmann, Astrid; John, Ulrich; Rudan, Igor; Hayward, Caroline; Wright, Alan F; Kolcic, Ivana; Wright, Benjamin J; Thompson, John R; Balmforth, Anthony J; Hall, Alistair S; Samani, Nilesh J; Anderson, Carl A; Ahmad, Tariq; Mathew, Christopher G; Parkes, Miles; Satsangi, Jack; Caulfield, Mark; Munroe, Patricia B; Farrall, Martin; Dominiczak, Anna; Worthington, Jane; Thomson, Wendy; Eyre, Steve; Barton, Anne; Mooser, Vincent; Francks, Clyde; Marchini, Jonathan

    2010-05-01

    Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.

  19. The association between B vitamins supplementation and adverse cardiovascular events: a meta-analysis

    PubMed Central

    Li, Wen-Feng; Zhang, Dan-Dan; Xia, Ji-Tian; Wen, Shan-Fan; Guo, Jun; Li, Zi-Cheng

    2014-01-01

    This study is to explore the association of adverse cardiovascular events with B vitamins supplementation. Rev.Man 5.1 and Stata 11.0 software were applied for the meta-analysis. The number of cardiovascular events was collected and calculated using indicates of odds ratio and 95% confidence intervals in a fixed-effects or a random-effects model when appropriate. The study includes 15 studies which consists of 37,358 study objects (experimental group: 19,601; control group: 17,757). This study showed that the pooled ORs was 1.01 (95% CI = 0.96~1.06, P > 0.05) for objects with Experimental group (B vitamins supplementation) vs. Control group (placebo or regular treatment), which suggests no significant differences were found in the overall effect of the number of cardiovascular events between the two groups. Further stratification of subgroup analysis indicates no significant differences were found between the two groups as well. There were also no publication bias existing by the Egger’s linear regression test (P > 0.05). Our result indicates that the number of cardiovascular events in experimental group using B vitamins supplementation during the treatment is equal to placebo or regular treatment group thus further studies is necessary. PMID:25232372

  20. 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.

  1. Association between MTHFD1 G1958A Polymorphism and Neural Tube Defects Susceptibility: A Meta-Analysis

    PubMed Central

    Jiang, Jianxin; Zhang, Yanfei; Wei, Liang; Sun, Zhiyang; Liu, Zhongmin

    2014-01-01

    Objectives The methylenetetrahydrofolate dehydrogenase (MTHFD1) gene, as one of the key genes involved in the folate pathway, has been reported to play a critical role in the pathogenesis of neural tube defects (NTDs). However, the results of published studies are contradictory and inconclusive. Thus, this meta-analysis aimed to evaluate the effect of the common polymorphism in the MTHFD1 gene, the G1958A (R653Q, dbSNP ID: rs2236225) variant, on the risk of NTDs in all eligible studies. Methods Relevant literature published before January 3, 2014 was retrieved from the MEDLINE, EMBASE, Cochrane Library, and CBM databases. Pooled crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between the MTHFD1 G1958A polymorphism and NTDs risk. Results We performed a meta-analysis of nine studies with a total of 4,302 NTDs patients and 4,238 healthy controls. Our results demonstrated a significant correlation between the MTHFD1 G1958A polymorphism and NTDs in an overall meta-analysis. For family-based studies, the study subjects were classified as NTD cases, mothers with NTDs offspring, and fathers with NTDs offspring. We found no association between any of the fathers’ genotypes and NTDs, whereas there was a clear excess of the 1958A allele in the mothers of children with NTDs compared with controls individuals. Conclusions In summary, our meta-analysis strongly suggests that the MTHFD1 G1958A polymorphism might be associated with maternal risk for NTDs in Caucasian populations. However, the evidence of this association should be interpreted with caution due to the selective nature of publication of genetic association studies. PMID:24977710

  2. 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.; Zillikens, M. Carola; Amouyel, Philippe; Boehm, Bernhard O.; Boerwinkle, Eric; Boomsma, Dorret I.; Caulfield, Mark J.; Chanock, Stephen J.; Cupples, L. Adrienne; Cusi, Daniele; Dedoussis, George V.; Erdmann, Jeanette; Eriksson, Johan G.; Franks, Paul W.; Froguel, Philippe; Gieger, Christian; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hengstenberg, Christian; Hicks, Andrew A.; Hingorani, Aroon; Hinney, Anke; Hofman, Albert; Hovingh, Kees G.; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Keinanen-Kiukaanniemi, Sirkka M.; Kiemeney, Lambertus A.; Kuh, Diana; Laakso, Markku; Lehtimäki, Terho; Levinson, Douglas F.; Martin, Nicholas G.; Metspalu, Andres; Morris, Andrew D.; Nieminen, Markku S.; Njølstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J.; Ouwehand, Willem H.; Palmer, Lyle J.; Penninx, Brenda; Power, Chris; Province, Michael A.; Psaty, Bruce M.; Qi, Lu; Rauramaa, Rainer; Ridker, Paul M.; Ripatti, Samuli; Salomaa, Veikko; Samani, Nilesh J.; Snieder, Harold; Sørensen, Thorkild I.A.; Spector, Timothy D.; Stefansson, Kari; Tönjes, Anke; Tuomilehto, Jaakko; Uitterlinden, André G.; Uusitupa, Matti; van der Harst, Pim; Vollenweider, Peter; Wallaschofski, Henri; Wareham, Nicholas J.; Watkins, Hugh; Wichmann, H.-Erich; Wilson, James F.; Abecasis, Goncalo R.; Assimes, Themistocles L.; Barroso, Inês; Boehnke, Michael; Borecki, Ingrid B.; Deloukas, Panos; Fox, Caroline S.; Frayling, Timothy; Groop, Leif C.; Haritunian, Talin; Heid, Iris M.; Hunter, David; Kaplan, Robert C.; Karpe, Fredrik; Moffatt, Miriam; Mohlke, Karen L.; O’Connell, Jeffrey R.; Pawitan, Yudi; Schadt, Eric E.; Schlessinger, David; Steinthorsdottir, Valgerdur; Strachan, David P.; Thorsteinsdottir, Unnur; van Duijn, Cornelia M.; Visscher, Peter M.; Di Blasio, Anna Maria; Hirschhorn, Joel N.; Lindgren, Cecilia M.; Morris, Andrew P.; Meyre, David; Scherag, André; McCarthy, Mark I.; Speliotes, Elizabeth K.; North, Kari E.; Loos, Ruth J.F.; Ingelsson, Erik; Hirschhorn, Joel; North, Kari E.; Ingelsson, Erik; Lin, Dan-Yu

    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

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

    PubMed Central

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

    2016-01-01

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

  4. SDF1-3′A polymorphism is associated with increased risk of hematological malignancy: a meta-analysis

    PubMed Central

    Zhang, Xiaowen; Fan, Yang; Li, Zhijie

    2017-01-01

    CXCL12 (also named SDF1), a member of the chemokine family, has been demonstrated to play an important role in the progression of multiple types of hematological malignancy. Several recent studies have shown that SDF1-3′A polymorphism (rs1801157) is associated with susceptibility to hematological malignancy, but published studies’ results are disputed. Therefore, we performed a meta-analysis to evaluate the relationship between SDF1-3′A polymorphism and the risk of hematological malignancy based on the existing literature. We carried out a comprehensive literature search using the Web of Science, PubMed, Cochrane Library, Chinese Wan Fang, and Chinese National Knowledge Infrastructure databases. And the raw data were extracted and calculated in standard steps of meta-analysis. Overall, nine qualified studies containing 1,576 cases and 1,674 controls were included in the ultimate meta-analysis. The pooled results displayed that AA genotype significantly increased the risk of hematological malignancy. The result of subgroup analysis further indicated that SDF1-3′A polymorphism was significantly associated with increased risk of chronic myeloid leukemia, Hodgkin’s lymphoma and multiple myeloma, but was not associated with increased risk of acute myeloid leukemia and non-Hodgkin’s lymphoma. In addition, SDF1-3′A polymorphism was associated with increased risk of hematological malignancy in Africans and Asians, but not in Caucasians. In conclusion, our meta-analysis firstly demonstrated that SDF1-3′A polymorphism may be associated with increased risk of hematological malignancy, especially for chronic myeloid leukemia, Hodgkin’s lymphoma, multiple myeloma and the non-Caucasian population. Nevertheless, these conclusions should be reconfirmed by more evidence from large sample sized studies. PMID:28352190

  5. Association between the XRCC3 polymorphisms and breast cancer risk: meta-analysis based on case-control studies.

    PubMed

    He, Xiao-Feng; Wei, Wu; Su, Jiao; Yang, Zi-Xuan; Liu, Yi; Zhang, Ying; Ding, Da-Peng; Wang, Wei

    2012-05-01

    The previous published data on the association between X-ray repair cross-complementing group 3 (XRCC3) T241M, A4541G, and A17893G polymorphisms and breast cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between breast cancer and XRCC3 T241M (21,910 cases and 23,961 controls), A4541G (9,633 cases and 10,994 controls), and A17893G polymorphisms (10,761 cases and 12,235 controls) in different inheritance models. When all the eligible studies were pooled into the meta-analysis of XRCC3 T241M polymorphism, significantly increased risk of breast cancer was observed in recessive model (odds' ratio [OR] = 1.10, 95% confidence interval [CI] = 1.04-1.16) and in additive model (OR = 1.10, 95% CI = 1.03-1.16). No significant association was found between A4541G polymorphism and breast cancer risk. When all the eligible studies were pooled into the meta-analysis of XRCC3 A17893G polymorphism, no significant association was found in any genetic model. Additionally, when one study was deleted in the sensitive analysis, the results of XRCC3 A17893G were changed in the additive model (OR = 0.90, 95% CI = 0.82-0.99) and dominant model (OR = 0.94, 95% CI = 0.89-0.99). In summary, this meta-analysis indicates that T241M polymorphism show an increased breast cancer risk and A17893G polymorphism may be associated with decreased breast cancer risk. A study with the larger sample size is needed to further evaluated gene-environment interaction on XRCC3 T241M, A4541G, and A17893G polymorphisms and breast cancer risk.

  6. 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

    2013-08-08

    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.

  7. 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

  8. Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis.

    PubMed

    Mbanefo, Evaristus Chibunna; Ahmed, Ali Mahmoud; Titouna, Afaf; Elmaraezy, Ahmed; Trang, Nguyen Thi Huyen; Phuoc Long, Nguyen; Hoang Anh, Nguyen; Diem Nghi, Tran; The Hung, Bui; Van Hieu, Mai; Ky Anh, Nguyen; Huy, Nguyen Tien; Hirayama, Kenji

    2017-04-06

    Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency overlaps with malaria endemicity although it predisposes carriers to hemolysis. This fact supports the protection hypothesis against malaria. The aim of this systematic review is to assess the presence and the extent of protective association between G6PD deficiency and malaria. Thirteen databases were searched for papers reporting any G6PD alteration in malaria patients. Twenty-eight of the included 30 studies were eligible for the meta-analysis. Results showed absence of negative association between G6PD deficiency and uncomplicated falciparum malaria (odds ratio (OR), 0.77; 95% confidence interval (CI), 0.59-1.02; p = 0.07). However, this negative association happened in Africa (OR, 0.59; 95% CI, 0.40-0.86; p = 0.007) but not in Asia (OR, 1.24; 95% CI, 0.96-1.61; p = 0.10), and in the heterozygotes (OR, 0.70; 95% CI, 0.57-0.87; p = 0.001) but not the homo/hemizygous (OR, 0.70; 95% CI, 0.46-1.07; p = 0.10). There was no association between G6PD deficiency and total severe malaria (OR, 0.82; 95% CI, 0.61-1.11; p = 0.20). Similarly, there was no association with other malaria species. G6PD deficiency can potentially protect against uncomplicated malaria in African countries, but not severe malaria. Interestingly, this protection was mainly in heterozygous, being x-linked thus related to gender.

  9. Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis

    PubMed Central

    Mbanefo, Evaristus Chibunna; Ahmed, Ali Mahmoud; Titouna, Afaf; Elmaraezy, Ahmed; Trang, Nguyen Thi Huyen; Phuoc Long, Nguyen; Hoang Anh, Nguyen; Diem Nghi, Tran; The Hung, Bui; Van Hieu, Mai; Ky Anh, Nguyen; Huy, Nguyen Tien; Hirayama, Kenji

    2017-01-01

    Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency overlaps with malaria endemicity although it predisposes carriers to hemolysis. This fact supports the protection hypothesis against malaria. The aim of this systematic review is to assess the presence and the extent of protective association between G6PD deficiency and malaria. Thirteen databases were searched for papers reporting any G6PD alteration in malaria patients. Twenty-eight of the included 30 studies were eligible for the meta-analysis. Results showed absence of negative association between G6PD deficiency and uncomplicated falciparum malaria (odds ratio (OR), 0.77; 95% confidence interval (CI), 0.59–1.02; p = 0.07). However, this negative association happened in Africa (OR, 0.59; 95% CI, 0.40–0.86; p = 0.007) but not in Asia (OR, 1.24; 95% CI, 0.96–1.61; p = 0.10), and in the heterozygotes (OR, 0.70; 95% CI, 0.57–0.87; p = 0.001) but not the homo/hemizygous (OR, 0.70; 95% CI, 0.46–1.07; p = 0.10). There was no association between G6PD deficiency and total severe malaria (OR, 0.82; 95% CI, 0.61–1.11; p = 0.20). Similarly, there was no association with other malaria species. G6PD deficiency can potentially protect against uncomplicated malaria in African countries, but not severe malaria. Interestingly, this protection was mainly in heterozygous, being x-linked thus related to gender. PMID:28382932

  10. Association between Myocardial Infarction and Periodontitis: A Meta-Analysis of Case-Control Studies.

    PubMed

    Shi, Quan; Zhang, Bin; Huo, Na; Cai, Chuan; Liu, Hongchen; Xu, Juan

    2016-01-01

    Background and Objective: Many clinical researches have been carried out to investigate the relationship between myocardial infarction (MI) and periodontitis. Despite most of them indicated that the periodontitis may be associated with an increased risk of MI, the findings and study types of these studies have been inconsistent. The goal of this meta-analysis was to critically assess the strength of the association between MI and periodontitis in case-control studies. Methods: PubMed and the Cochrane Library were searched for eligible case-control studies reporting relevant parameters that compared periodontal status between MI and control subjects. The odds ratios (ORs) and 95% confidence intervals (CIs) from each study were pooled to estimate the strength of the association between MI and periodontitis. The mean differences and 95% CIs for periodontal-related parameters were calculated to determine their overall effects. Results: Seventeen studies including a total of 3456 MI patients and 3875 non-MI control subjects were included. The pooled OR for the association between MI and periodontitis was 2.531 (95% CI: 1.927-3.324). The mean differences (95% CIs) for clinical attachment loss, probing depth, bleeding on probing, plaque index, and the number of missing teeth were 1.000 (0.726-1.247), 1.209 (0.538-1.880), 0.342 (0.129-0.555), 0.383 (0.205-0.560), and 4.122 (2.012-6.232), respectively. Conclusion: With the current evidence, the results support the presence of a significant association between MI and periodontitis. Moreover, MI patients had worse periodontal and oral hygiene status and fewer teeth than did control subjects. More high-quality and well-designed studies focusing on the casual relationship between MI and periodontitis should be conducted in the future.

  11. Association between dietary patterns and coronary heart disease: a meta-analysis of prospective cohort studies

    PubMed Central

    Hou, Lina; Li, Fei; Wang, Yuanyuan; Ou, Zejin; Xu, Dingli; Tan, Wanlong; Dai, Meng

    2015-01-01

    The associations of dietary patterns with coronary heart disease (CHD) risk remain unclear. Thereby, a meta-analysis was conducted to examine potential relations between dietary patterns and CHD. PubMed and EMBASE databases were searched up to March 2014 for eligible prospective cohort studies regarding the relationships between common dietary patterns and CHD. Random-effects models were applied to calculate the summary relative risk estimates (SRRE) for the highest versus the lowest category of dietary pattern. Sensitivity analyses were conducted and publication bias was assessed using Begg or Egger’s tests. Twelve prospective cohort studies were included involving 409,780 participants and 6298 CHD cases. There was an inverse association between prudent/healthy dietary pattern and CHD risk (SRRE = 0.80, 95% CI: 0.74-0.87, P-value for heterogeneity = 0.497, I2 = 0%). Furthermore, no significant association was observed between western/unhealthy dietary pattern and risk of CHD (SRRE = 1.05, 95% CI: 0.86-1.27, P-value for heterogeneity = 0.007, I2 = 61.9%). However, increased risk was detected between western/unhealthy dietary pattern and CHD in the United States (USA) (SRRE = 1.45, 95% CI: 1.15-1.82, P-value for heterogeneity = 0.930, I2 = 0%). In conclusion, our analysis provides evidence of an inverse association between prudent/healthy dietary pattern and CHD risk, and suggests null association between western/unhealthy dietary pattern and CHD. However, greater adherence to western/unhealthy pattern possibily increases by 45% the risk of CHD in USA. Further efforts are warranted to confirm these findings and clarify the role of dietary patterns and CHD risk. PMID:25785058

  12. BDNF Val66Met and cognition: all, none, or some? A meta-analysis of the genetic association.

    PubMed

    Mandelman, S D; Grigorenko, E L

    2012-03-01

    The Val66Met, G196A (rs6265) polymorphism in the brain-derived neurotrophic factor gene, BDNF, located at 11p13, has been associated with a wide range of cognitive functions. Yet, the pattern of results is complex and conflicting. In this study, we conducted a meta-analysis that included 23 publications containing 31 independent samples comprised of 7095 individuals. The phenotypes that were examined in this analysis covered a wide variety of cognitive functions and included indicators of general cognitive ability, memory, executive function, visual processing skills and cognitive fluency. The meta-analysis did not establish significant genetic associations between the Val66Met polymorphism and any of the phenotypes that were included.

  13. Association of tumor necrosis factor-α gene G-308A polymorphism with dilated cardiomyopathy: a meta-analysis.

    PubMed

    Luo, Rong; Li, Xiaoping; Fan, Xiongwei; Yuan, Wuzhou; Wu, Xiushan

    2013-03-01

    Published data on the association between tumor necrosis factor-α (TNF-α) G-308A gene polymorphism and dilated cardiomyopathy (DCM) risk are inconclusive. To clarify the association of TNF-α G-308A gene polymorphism and DCM, a meta-analysis of case-control studies was performed. Some databases, such as PubMed and Embase, were searched to indentify related studies. Search terms included dilated cardiomyopathy, tumor necrosis factor-alpha or TNF-α or TNF alpha or tumor necrosis factor alpha, and polymorphism or mutation. Eight case-control studies involving 1487 DCM cases and 1734 normal controls were included in the meta-analysis to assess the purported association between the TNF-α G-308A gene polymorphism and the risk of DCM. A dominant genetic model was used and the comparison of GA/AA genotype versus GG genotype was performed in the present meta-analysis. The odds ratio was 1.42 (95% confidence interval: 1.05, 1.93, P=0.02), manifesting frequency of the TNF-α-308 GA/AA genotype was higher in DCM patients than the control group. TNF-α G-308A nucleotide transition might be associated with the risk of DCM.

  14. Association between individual differences in non-symbolic number acuity and math performance: a meta-analysis.

    PubMed

    Chen, Qixuan; Li, Jingguang

    2014-05-01

    Many recent studies have examined the association between number acuity, which is the ability to rapidly and non-symbolically estimate the quantity of items appearing in a scene, and symbolic math performance. However, various contradictory results have been reported. To comprehensively evaluate the association between number acuity and symbolic math performance, we conduct a meta-analysis to synthesize the results observed in previous studies. First, a meta-analysis of cross-sectional studies (36 samples, N = 4705) revealed a significant positive correlation between these skills (r = 0.20, 95% CI = [0.14, 0.26]); the association remained after considering other potential moderators (e.g., whether general cognitive abilities were controlled). Moreover, a meta-analysis of longitudinal studies revealed 1) that number acuity may prospectively predict later math performance (r = 0.24, 95% CI = [0.11, 0.37]; 6 samples) and 2) that number acuity is retrospectively correlated to early math performance as well (r = 0.17, 95% CI = [0.07, 0.26]; 5 samples). In summary, these pieces of evidence demonstrate a moderate but statistically significant association between number acuity and math performance. Based on the estimated effect sizes, power analyses were conducted, which suggested that many previous studies were underpowered due to small sample sizes. This may account for the disparity between findings in the literature, at least in part. Finally, the theoretical and practical implications of our meta-analytic findings are presented, and future research questions are discussed.

  15. Association between a functional genetic polymorphism (rs2230199) and age-related macular degeneration risk: a meta-analysis.

    PubMed

    Zhang, M X; Zhao, X F; Ren, Y C; Geng, T T; Yang, H; Feng, T; Jin, T B; Chen, C

    2015-10-16

    The association between the rs2230199 C>G single nucleotide polymorphism (SNP) in complement component 3 and age-related macular degeneration (AMD) risk has been examined extensively but the results are not consistent among studies. The aim of this study was to perform a meta-analysis of all available studies on this SNP in relation to AMD. The comprehensive databases of PubMed, Medline, Web of Knowledge, CNKI, and Google Scholar were searched for case-control studies investigating the association between the rs2230199 polymorphism and AMD susceptibility. ORs with 95%CIs were estimated to assess the association. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were also performed. A total of 15 published studies including 5593 cases and 5181 controls were used in this meta-analysis. Overall, the rs2230299 SNP was significantly associated with the risk of AMD in the overall population under the additive model (OR = 1.571, 95%CI = 1.414-1.745, P = 0.000), dominant model (OR = 1.681, 95%CI = 1.521-1.858, P = 0.000), and allelic model (OR = 1.597, 95%CI = 1.470-1.734, P = 0.000). In the subgroup analysis by ethnicity, the same results were found in Caucasian populations, while no significant correlations were found in Asian populations for all comparison models. In conclusion, our meta-analysis provides evidence that the rs2230199 polymorphism contributes to the development of AMD. Further large-scale multicenter epidemiological studies are warranted to confirm this finding.

  16. Revealing the association between cerebrovascular accidents and ambient temperature: a meta-analysis

    NASA Astrophysics Data System (ADS)

    Zorrilla-Vaca, Andrés; Healy, Ryan Jacob; Silva-Medina, Melissa M.

    2016-10-01

    The association between cerebrovascular accidents (CVA) and weather has been described across several studies showing multiple conflicting results. In this paper, we aim to conduct a meta-analysis to further clarify this association, as well as to find the potential sources of heterogeneity. PubMed, EMBASE, and Google Scholar were searched from inception through 2015, for articles analyzing the correlation between the incidence of CVA and temperature. A pooled effect size (ES) was estimated using random effects model and expressed as absolute values. Subgroup analyses by type of CVA were also performed. Heterogeneity and influence of covariates—including geographic latitude of the study site, male percentage, average temperature, and time interval—were assessed by meta-regression analysis. Twenty-six articles underwent full data extraction and scoring. A total of 19,736 subjects with CVA from 12 different countries were included and grouped as ischemic strokes (IS; n = 14,199), intracerebral hemorrhages (ICH; n = 3798), and subarachnoid hemorrhages (SAH; n = 1739). Lower ambient temperature was significantly associated with increase in incidence of overall CVA when using unadjusted (pooled ES = 0.23, P < 0.001) and adjusted data (pooled ES = 0.03, P = 0.003). Subgroup analyses showed that lower temperature has higher impact on the incidence of ICH (pooled ES = 0.34, P < 0.001), than that of IS (pooled ES = 0.22, P < 0.001) and SAH (pooled ES = 0.11, P = 0.012). In meta-regression analysis, the geographic latitude of the study site was the most influencing factor on this association (Z-score = 8.68). Synthesis of the existing data provides evidence supporting that a lower ambient temperature increases the incidence of CVA. Further population-based studies conducted at negative latitudes are needed to clarify the influence of this factor.

  17. Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels

    PubMed Central

    Kwan, Johnny S.H.; Hsu, Yi-Hsiang; Cheung, Ching-Lung; Dupuis, Josée; Saint-Pierre, Aude; Eriksson, Joel; Handelman, Samuel K.; Aragaki, Aaron; Karasik, David; Pramstaller, Peter P.; Kooperberg, Charles; Lacroix, Andrea Z.; Larson, Martin G.; Lau, Kam-Shing; Lorentzon, Mattias; Pichler, Irene; Sham, Pak C.; Taliun, Daniel; Vandenput, Liesbeth; Kiel, Douglas P.; Hicks, Andrew A.; Jackson, Rebecca D.; Ohlsson, Claes; Benjamin, Emelia J.; Kung, Annie W.C.

    2014-01-01

    Osteoprotegerin (OPG) is involved in bone homeostasis and tumor cell survival. Circulating OPG levels are also important biomarkers of various clinical traits, such as cancers and atherosclerosis. OPG levels were measured in serum or in plasma. In a meta-analysis of genome-wide association studies in up to 10 336 individuals from European and Asian origin, we discovered that variants >100 kb upstream of the TNFRSF11B gene encoding OPG and another new locus on chromosome 17q11.2 were significantly associated with OPG variation. We also identified a suggestive locus on chromosome 14q21.2 associated with the trait. Moreover, we estimated that over half of the heritability of OPG levels could be explained by all variants examined in our study. Our findings provide further insight into the genetic regulation of circulating OPG levels. PMID:25080503

  18. A meta-analysis of the association of serum ischaemia-modified albumin levels with human hypothyroidism and hyperthyroidism

    PubMed Central

    Reddy, Varikasuvu Seshadri; Bukke, Suman; Mahato, Khageshwar; Kumar, Vinod; Reddy, Netala Vasudeva; Munikumar, Manne; Vodelu, Bramahanapally

    2016-01-01

    Serum levels of ischaemia-modified albumin (IMA) have been studied as a novel and simple measure of oxidative stress (OXS) in different thyroid pathologies. However, results of available studies in the literature were not consistent. This meta-analysis was attempted to quantify the overall effect size for serum IMA levels in human hypothyroidism (HT) and hyperthyroidism (HYT) and to study its associations with the thyroid profile. Databases of PubMed/Medline, EMBASE, Google Scholar, Web of Science and Science Direct were searched for articles. Data on serum IMA levels in HT, HYT patients and euthyroid controls were extracted to compute standardized mean differences (SMD) by the random-effects model. The associations between IMA and thyroid profile were computed by the meta-analysis of correlation coefficients. IMA levels in HT patients (SMD=1.12; Z=2.76; P=0.006) and HYT patients (SMD=1.64; Z=2.57; P=0.01) were significantly higher than in euthyroid controls and the thyroid treatment showed a favourble effect on serum IMA levels. There were strong and significant correlations between IMA and hormonal status in HT and HYT groups. This meta-analysis showing increased IMA level in both HT and HYT patients and its association with thyroid profile suggests that serum IMA could be used as a simple measure of increased OXS in thyroid dysfunction. PMID:27920278

  19. A meta-analysis of the association of serum ischaemia-modified albumin levels with human hypothyroidism and hyperthyroidism.

    PubMed

    Reddy, Varikasuvu Seshadri; Bukke, Suman; Mahato, Khageshwar; Kumar, Vinod; Reddy, Netala Vasudeva; Munikumar, Manne; Vodelu, Bramahanapally

    2017-02-28

    Serum levels of ischaemia-modified albumin (IMA) have been studied as a novel and simple measure of oxidative stress (OXS) in different thyroid pathologies. However, results of available studies in the literature were not consistent. This meta-analysis was attempted to quantify the overall effect size for serum IMA levels in human hypothyroidism (HT) and hyperthyroidism (HYT) and to study its associations with the thyroid profile. Databases of PubMed/Medline, EMBASE, Google Scholar, Web of Science and Science Direct were searched for articles. Data on serum IMA levels in HT, HYT patients and euthyroid controls were extracted to compute standardized mean differences (SMD) by the random-effects model. The associations between IMA and thyroid profile were computed by the meta-analysis of correlation coefficients. IMA levels in HT patients (SMD=1.12; Z=2.76; P=0.006) and HYT patients (SMD=1.64; Z=2.57; P=0.01) were significantly higher than in euthyroid controls and the thyroid treatment showed a favourble effect on serum IMA levels. There were strong and significant correlations between IMA and hormonal status in HT and HYT groups. This meta-analysis showing increased IMA level in both HT and HYT patients and its association with thyroid profile suggests that serum IMA could be used as a simple measure of increased OXS in thyroid dysfunction.

  20. HBV X gene point mutations are associated with the risk of hepatocellular carcinoma: A systematic review and meta-analysis

    PubMed Central

    WANG, YULAN; ZENG, LI; CHEN, WEIQING

    2016-01-01

    Previous evidence suggests that the accumulation of the hepatitis B virus (HBV) X gene region point mutations may be associated with the development of hepatocellular carcinoma (HCC). However, the pathogenesis of HCC remains to be elucidated. The aim of the present meta-analysis was to investigate the association between the HBV X gene point mutations and the risk of HCC. Studies were collected regarding the association between HBV X gene point mutations and the risk of HCC, which were identified in PubMed, EMBASE and China National Knowledge Infrastructure databases. The results were evaluated by use of odds ratios (ORs) and its 95% confidence intervals (CIs), which were pooled by random or fixed effects. A total of 11 studies involving 2,502 patients were included in this meta-analysis. Statistical summary ORs of HBV X gene point mutations were obtained for T1653 (OR, 3.11; 95% CI, 2.22–4.36), V1753 (OR, 2.55; 95% CI, 1.66–3.92), and T1762/A1764 (OR, 4.49; 95% CI, 2.86–7.07). HBV X gene point mutations T1653, V1753 and T1762/A1764 could increase the risk of HCC significantly, particularly the T1762/A1764 double mutations. These mutations may be predictive for hepatocarcinogenesis. However, these results of the meta-analysis should be treated carefully due to a low level of evidence. PMID:27284442

  1. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection.

    PubMed

    Brown, Kevin A; Khanafer, Nagham; Daneman, Nick; Fisman, David N

    2013-05-01

    The rising incidence of Clostridium difficile infection (CDI) could be reduced by lowering exposure to high-risk antibiotics. The objective of this study was to determine the association between antibiotic class and the risk of CDI in the community setting. The EMBASE and PubMed databases were queried without restriction to time period or language. Comparative observational studies and randomized controlled trials (RCTs) considering the impact of exposure to antibiotics on CDI risk among nonhospitalized populations were considered. We estimated pooled odds ratios (OR) for antibiotic classes using random-effect meta-analysis. Our search criteria identified 465 articles, of which 7 met inclusion criteria; all were observational studies. Five studies considered antibiotic risk relative to no antibiotic exposure: clindamycin (OR = 16.80; 95% confidence interval [95% CI], 7.48 to 37.76), fluoroquinolones (OR = 5.50; 95% CI, 4.26 to 7.11), and cephalosporins, monobactams, and carbapenems (CMCs) (OR = 5.68; 95% CI, 2.12 to 15.23) had the largest effects, while macrolides (OR = 2.65; 95% CI, 1.92 to 3.64), sulfonamides and trimethoprim (OR = 1.81; 95% CI, 1.34 to 2.43), and penicillins (OR = 2.71; 95% CI, 1.75 to 4.21) had lower associations with CDI. We noted no effect of tetracyclines on CDI risk (OR = 0.92; 95% CI, 0.61 to 1.40). In the community setting, there is substantial variation in the risk of CDI associated with different antimicrobial classes. Avoidance of high-risk antibiotics (such as clindamycin, CMCs, and fluoroquinolones) in favor of lower-risk antibiotics (such as penicillins, macrolides, and tetracyclines) may help reduce the incidence of CDI.

  2. Association between Helicobacter pylori and end-stage renal disease: A meta-analysis

    PubMed Central

    Wijarnpreecha, Karn; Thongprayoon, Charat; Nissaisorakarn, Pitchaphon; Lekuthai, Natasorn; Jaruvongvanich, Veeravich; Nakkala, Kiran; Rajapakse, Ridhmi; Cheungpasitporn, Wisit

    2017-01-01

    AIM To investigate the prevalence and association of Helicobacter pylori (H. pylori) with end-stage renal disease (ESRD). METHODS SA comprehensive literature search was completed from inception until October 2016. Studies that reported prevalence, relative risks, odd ratios, hazard ratios or standardized incidence ratio of H. pylori among ESRD patients were included. Participants without H. pylori were used as comparators to assess the association between H. pylori infection and ESRD. Pooled risk ratios and 95%CI was calculated using a random-effect model. Adjusted point estimates from each study were combined by the generic inverse variance method of DerSimonian and Laird. RESULTS Of 4546 relevant studies, thirty-seven observational studies met all inclusion criteria. Thirty-five cross-sectional studies were included in the analyses to assess the prevalence and association of H. pylori with ESRD. The estimated prevalence of H. pylori among ESRD patients was 44% (95%CI: 40%-49%). The pooled RR of H. pylori in patients with ESRD was 0.77 (95%CI: 0.59-1.00) when compared with the patients without ESRD. Subgroup analysis showed significantly reduced risk of H. pylori in adult ESRD patients with pooled RR of 0.71 (95%CI: 0.55-0.94). The data on the risk of ESRD in patients with H. pylori were limited. Two cohort studies were included to assess the risk of ESRD in patients with H. pylori. The pooled risk RR of ESRD in patients with H. pylori was 0.61 (95%CI: 0.03-12.20). CONCLUSION The estimated prevalence of H. pylori in ESRD patients is 44%. Our meta-analysis demonstrates a decreased risk of H. pylori in adult ESRD patients. PMID:28293097

  3. Meta-analysis for genome-wide association studies using case-control design: application and practice

    PubMed Central

    2016-01-01

    This review aimed to arrange the process of a systematic review of genome-wide association studies in order to practice and apply a genome-wide meta-analysis (GWMA). The process has a series of five steps: searching and selection, extraction of related information, evaluation of validity, meta-analysis by type of genetic model, and evaluation of heterogeneity. In contrast to intervention meta-analyses, GWMA has to evaluate the Hardy–Weinberg equilibrium (HWE) in the third step and conduct meta-analyses by five potential genetic models, including dominant, recessive, homozygote contrast, heterozygote contrast, and allelic contrast in the fourth step. The ‘genhwcci’ and ‘metan’ commands of STATA software evaluate the HWE and calculate a summary effect size, respectively. A meta-regression using the ‘metareg’ command of STATA should be conducted to evaluate related factors of heterogeneities. PMID:28092928

  4. Meta-analysis for genome-wide association studies using case-control design: application and practice.

    PubMed

    Shim, Sungryul; Kim, Jiyoung; Jung, Wonguen; Shin, In-Soo; Bae, Jong-Myon

    2016-01-01

    This review aimed to arrange the process of a systematic review of genome-wide association studies in order to practice and apply a genome-wide meta-analysis (GWMA). The process has a series of five steps: searching and selection, extraction of related information, evaluation of validity, meta-analysis by type of genetic model, and evaluation of heterogeneity. In contrast to intervention meta-analyses, GWMA has to evaluate the Hardy-Weinberg equilibrium (HWE) in the third step and conduct meta-analyses by five potential genetic models, including dominant, recessive, homozygote contrast, heterozygote contrast, and allelic contrast in the fourth step. The 'genhwcci' and 'metan' commands of STATA software evaluate the HWE and calculate a summary effect size, respectively. A meta-regression using the 'metareg' command of STATA should be conducted to evaluate related factors of heterogeneities.

  5. Association of fruit and vegetables with the risk of nasopharyngeal cancer: Evidence from a meta-analysis

    PubMed Central

    Jin, Jian; Ouyang, Zhiguo; Wang, Zhaoyan

    2014-01-01

    Quantification of the association between the intake of vegetables and fruit and risk of nasopharyngeal cancer (NPC) is controversial. Thus, we conducted a meta-analysis to assess the relationship between vegetables and fruit and NPC risk. Pertinent studies were identified by a search in PubMed, Web of Knowledge and Wan Fang Med Online. Random-effects models were used to calculate summary relative risks (RRs) and the corresponding 95% confidence intervals (CIs). Publication bias was estimated using Egger's regression asymmetry test. Finally, 15 articles comprising 8208 NPC cases were included in this meta-analysis. The combined results showed that there was significant association between vegetables and fruit intake and NPC risk. The pooled RRs were 0.60 (95% CI = 0.47–0.76) for vegetables and 0.63 (95% CI = 0.56–0.70) for fruit. No publication bias was detected. Our analysis indicated that intake of vegetables and fruit may have a protective effect on NPC. Since the potential biases and confounders could not be ruled out completely in this meta-analysis, further studies are needed. PMID:25008797

  6. Association of trauma exposure with proinflammatory activity: a transdiagnostic meta-analysis

    PubMed Central

    Tursich, M; Neufeld, R W J; Frewen, P A; Harricharan, S; Kibler, J L; Rhind, S G; Lanius, R A

    2014-01-01

    Exposure to psychological trauma (for example, childhood/early life adversity, exposure to violence or assault, combat exposure, accidents or natural disasters) is known to increase one's risk of developing certain chronic medical conditions. Clinical and population studies provide evidence of systemic inflammatory activity in trauma survivors with various psychiatric and nonpsychiatric conditions. This transdiagnostic meta-analysis quantitatively integrates the literature on the relationship of inflammatory biomarkers to trauma exposure and related symptomatology. We conducted random effects meta-analyses relating trauma exposure to log-transformed inflammatory biomarker concentrations, using meta-regression models to test the effects of study quality and psychiatric symptomatology on the inflammatory outcomes. Across k=36 independent samples and n=14 991 participants, trauma exposure was positively associated with C-reactive protein (CRP), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α (mean rs =0.2455, 0.3067, 0.2890, and 0.2998, respectively). No significant relationships were noted with fibrinogen, IL-2, IL-4, IL-8, or IL-10. In meta-regression models, the presence of psychiatric symptoms was a significant predictor of increased effect sizes for IL-1β and IL-6 (β=1.0175 and 0.3568, respectively), whereas study quality assessment scores were associated with increased effect sizes for IL-6 (β=0.3812). Positive correlations between inflammation and trauma exposure across a range of sample types and diagnoses were found. Although reviewed studies spanned an array of populations, research on any one specific psychiatric diagnosis was generally limited to one or two studies. The results suggest that chronic inflammation likely represents one potential mechanism underlying risk of health problems in trauma survivors. PMID:25050993

  7. The Association between Barrett’s Esophagus and Helicobacter pylori Infection: A Meta-Analysis

    PubMed Central

    Fischbach, Lori A.; Nordenstedt, Helena; Kramer, Jennifer R.; Gandhi, Subi; Dick-Onuoha, Sam; Lewis, Anthony; El-Serag, Hashem B.

    2011-01-01

    Objective The effect of Helicobacter pylori on Barrett’s esophagus is poorly understood. We conducted a meta-analysis to summarize the existing literature examining the effect that H pylori has on Barrett’s esophagus. Design We performed a comprehensive search to identify studies pertaining to the association between H pylori and Barrett’s esophagus. We conducted meta-regression analyses to identify sources of variation in the effect of H pylori on Barrett’s esophagus. Results Our analysis included a total of 49 studies that examined the effect of H pylori on Barrett’s esophagus and 7 studies that examined the effect of cag A positivity on Barrett’s esophagus. Overall, H pylori, and even more so cag A, tended to be protective for Barrett’s esophagus in most studies; however there was obvious heterogeneity across studies. The effect of H pylori on Barrett’s esophagus varied by geographic location and in the presence of selection and information biases. Only 4 studies were found without obvious selection and information bias, and these showed a protective effect of H pylori on Barrett’s esophagus (Relative Risk = 0.46 [95% CI: 0.35, 0.60]). Conclusions Estimates for the effect of H pylori on Barrett’s esophagus were heterogeneous across studies. We identified selection and information bias as potential sources of this heterogeneity. Few studies without obvious selection and information bias have been conducted to examine the effect of H pylori on Barrett’s esophagus, but in these, H pylori infection is associated with a reduced risk of Barrett’s esophagus. PMID:22515353

  8. 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

  9. 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…

  10. 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

  11. Meta-analysis of the association between dietary lycopene intake and ovarian cancer risk in postmenopausal women

    PubMed Central

    Li, Xinli; Xu, Jiuhong

    2014-01-01

    Accumulating evidence suggests the protective role of dietary lycopene against the risk of ovarian cancer due to its antioxidant activity, but not all relevant studies have deduced positive results. The aim of the present study was to investigate the exact relationship between dietary lycopene intake and ovarian cancer risk by conducting a meta-analysis. The 10 studies included in our meta-analysis were selected from the PubMed database, and final risk estimates were calculated by using a random-effects model. Our study demonstrated an insignificant reverse association between dietary lycopene and ovarian cancer risk (OR, 0.963; 95% CI, 0.859–1.080), and subgroup analysis stratified by study design, location, histological type of ovarian cancer, and length of dietary recall showed no statistically significant results. No heterogeneity was observed (p = 0.336, I2 = 11.6%). Our present meta-analysis suggests the potential role of dietary lycopene against the risk of ovarian cancer among postmenopausal women, which provides opportunity for developments in the prevention of ovarian cancer. PMID:24810584

  12. 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

  13. 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

  14. SULT1A1 Arg213His Polymorphism is Associated with Bladder Cancer Risk: A Meta-Analysis

    PubMed Central

    Li, Wencheng; Gu, Min

    2014-01-01

    Background The evidence of an association between the Sulfotransferase 1A1 (SULT1A1) Arg213His polymorphism (rs9282861) and bladder cancer risk is still conflicting. We conducted a meta-analysis to assess the association between this polymorphism and bladder cancer risk. Material/Methods PubMed, EMBASE, HuGE Navigator, and Web of Science databases were searched for correlative articles. The risk (odds ratio, OR) was used to estimate the association between SULT1A1 Arg213His polymorphism and bladder cancer risk. All of the studies used either fixed-effects or random-effects models. For assessing the credibility of an association, we applied the Venice criteria. Results Seven published case-control studies with 1688 cases and 2842 controls were included in this meta-analysis. There were 5 studies of Caucasians and 2 studies of Asians. Four studies reported data on smoking behavior. The percentage of Arg/Arg was higher in Asians and non-smokers than that in Caucasians and smokers, respectively. A significant association of this polymorphism with bladder cancer was found (OR=1.45, 95% CI 1.18–1.78, P=0.0004). In the subgroup analysis by ethnicity, a significant association was found among Caucasians (OR=1.43, 95% CI 1.16–1.77, P=0.0008) but not among Asians (OR=1.89, 95% CI 0.68–5.26, P=0.22). In the subgroup analysis by smoking behavior, increased bladder cancer risk was found in the smokers (OR=1.39, 95% CI 1.01–1.91, P=0.04) and non-smokers (OR=1.74, 95% CI 1.24–2.43, P=0.001). Conclusions In conclusion, this meta-analysis indicated that SULT1A1 Arg213His polymorphism is associated with bladder cancer risk. PMID:25194687

  15. 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

  16. 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.

  17. Association between the FCGR2A gene H131R polymorphism and risk of Kawasaki disease: a meta-analysis.

    PubMed

    Lin, L; Wang, S Y; Yang, S B; Xiao, F C

    2015-06-11

    Several previous studies have investigated whether the FCGR2A gene H131R polymorphism confers an increased risk of Kawasaki disease (KD), but conflicting results have been reported. To further explore the association of this polymorphism with KD susceptibility, we performed an extensive search of relevant studies and conducted a meta-analysis to obtain a more precise estimate of risk. Systematic searches of the electronic databases Embase, PubMed, and Google Scholar were performed to identify relevant studies. Odds ratios (ORs) and their 95% confidence intervals (CIs) were used for statistical analysis. Six studies were included in the meta-analysis, involving 1709 patients with KD and 3207 controls. Significant association was found between the FCGR2A gene H131R polymorphism and KD risk in analysis of the total population (HH vs RR: OR = 1.97, 95%CI = 1.55-2.50; HH vs HR: OR = 1.38, 95%CI = 1.21-1.57; the dominant model: OR = 0.69, 95%CI = 0.60-0.78; and the recessive model: OR = 1.65, 95%CI = 1.32-2.07). In subgroup analysis by ethnicity, significant association was found between the H131R polymorphism and KD risk in Asians, but not in Caucasians. In addition, we found no significant association between the FCGR2A gene H131R polymorphism and risk of KD-associated coronary artery lesions. In conclusion, this meta-analysis suggested that the H131R polymorphism in the FCGR2A gene might be associated with susceptibility to KD in Asians.

  18. Association between the XRCC3 Thr241Met Polymorphism and Gastrointestinal Cancer Risk: A Meta-Analysis

    PubMed

    Sahami-Fard, Mohammad Hossein; Mousa Mayali, Ali Reza; Tajehmiri, Ahmad

    2016-10-01

    Background: The x-ray repair cross-complementing group 3 (XRCC3) encodes a protein involved in the homologous recombination repair (HRR) pathway for double-strand DNA repair. Associations of the XRCC3 Thr241Met polymorphism with various cancers have been widely reported. However, published data on links between XRCC3 Thr241Met and gastrointestinal (GI) cancer risk are inconsistent. Objective and Methods: A meta-analysis was conducted to characterize the relationship between XRCC3 Thr241Met polymorphisms and GI cancer risk. Pooled odds ratios (ORs) and 95.0% confidence intervals were assessed using random- or fixed- effect models for 28.0 relevant articles with 30.0 studies containing 7,649.0 cases and 11,123.0 controls. Results: The results of the overall meta-analysis suggested a borderline association between the XRCC3 Thr241Met polymorphism and GI cancer susceptibility (T vs. C: OR=1.18, 9 % CI=1.0–1.4, POR=0.04; TT vs. CT+CC: OR=1.3, 95 % CI=1.0–1.6, POR=0.04). After removing studies not conforming to Hardy–Weinberg equilibrium (HWE), however, this association disappeared (T vs. C: OR=1.00, 95 % CI=0.9–1.1, POR=0.96; TT vs. CT+CC: OR=0.9, 95 % CI=0.8–1.1, POR=0.72). When stratified by ethnicity, source of controls or cancer type, although some associations between XRCC3 Thr241Met polymorphism and GI cancer susceptibility were detected, these associations no longer existed after removing studies not conforming to HWE. Conclusion: Our meta-analysis suggests that the XRCC3 Thr241Met polymorphism is not associated with risk of GI cancer based on current evidence.

  19. Associations between polymorphisms of the ADIPOQ gene and hypertension risk: a systematic and meta-analysis

    PubMed Central

    Fan, Weina; Qu, Xiaowei; Li, Jing; Wang, Xingning; Bai, Yanping; Cao, Qingmei; Ma, Liqun; Zhou, Xiaoyao; Zhu, Wei; Liu, Wei; Ma, Qiang

    2017-01-01

    ADIPOQ gene polymorphisms have been indicated to be associated with hypertension; however, published studies have reported inconsistent results. Eligible studies were retrieved by searching the PubMed, Embase and China National Knowledge Infrastructure databases. The case group consisted of patients with hypertension, and the control group consisted of subjects with normal blood pressure. Based on eleven published articles, involving 4837 cases and 5618 controls, the pooled results from rs2241766 polymorphism showed increased risk in the allelic model (G VS T: OR = 1.16, 95%CI = 1.06–1.27), recessive model (GG VS GT + TT: OR = 1.34, 95%CI = 1.10–1.63), dominant model (GG + GT VS TT: OR = 1.15, 95%CI = 1.02–1.30) and homozygote model (GG VS TT: OR = 1.38, 95%CI = 1.21–1.69). In addition, rs266729 polymorphism showed increased risk for hypertension in the recessive model (GG VS GC + CC: OR = 1.43, 95%CI = 1.02–2.01). In the Caucasian subgroup, rs1501299 polymorphism showed decreased risk of hypertension in the allelic model (T VS G: OR = 0.75, 95%CI = 0.58–0.97), dominant model (TT + TG VS GG: OR = 0.83, 95%CI = 0.71–0.98) and heterozygote model (TG VS GG: OR = 0.82, 95%CI = 0.68–0.99). The rs2241766 polymorphism was associated with a significant increase in hypertension risk based on our analysis. Moreover, an increased risk of rs266729 in hypertension patients was also detected. Our meta-analysis suggests that the rs1501299 polymorphism may play a protective role in hypertension in Caucasian subgroup; however, this finding requires further study. PMID:28181566

  20. Association between cyclin D1 (CCND1) G870A polymorphism and gastric cancer risk: a meta-analysis

    PubMed Central

    Zhang, Yafei; Zeng, Xianling; Lu, Hongwei; Ji, Hong; Zhao, Enfa; Li, Yiming

    2016-01-01

    Published data on the association between cyclin D1 (CCND1) G870A polymorphism and gastric cancer (GC) risk are inconclusive. Thus, we conducted a meta-analysis to evaluate the relationship between CCND1 G870A polymorphism and GC risk. We searched PubMed, EMBASE, Web of science and the Cochrane Library up to June 12, 2015 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. Nine studies published from 2003 to 2014, with a total of 1813 cases and 2173 controls, were included in this meta-analysis. The pooled results showed that there was no association between CCND1 G870A polymorphism and GC risk in any genetic model. The subgroup analysis stratified by ethnicity showed an increased breast cancer risk in Caucasian based on heterozygote comparison (GA vs. GG: OR=1.49, 95% CI=1.06-2.10, P=0.02). We found the same association in population based (PB) stratified analyses by Source of controls (AA vs. GG: OR=1.39, 95% CI=1.01-1.93, 0.05). When stratifying by the type, Sex and H. pylori infection in dominant model, Interestingly, we found the opposite result in Male (AA + GA vs. GG: OR=0.5, 95% CI=0.33-0.76, P=0.001), there were no association between CCND1 G870A polymorphism and GC risk in any other subgroup. This meta-analysis suggests that CCND1 G870A polymorphism is a risk factor for susceptibility to GC in Caucasians and in general populations. While, CCND1 G870A polymorphism plays a possible protective effect in GC in Male. Further large scale multicenter epidemiological studies are warranted to confirm this finding. PMID:27623072

  1. Association between the -607 C > A polymorphism in interleukin-18 gene promoter with gastrointestinal cancer risk: a meta-analysis.

    PubMed

    Yao, J; Li, Z H; Li, Y X; Zhang, R; Zhang, D G; Xu, Z L; Wang, L S; Wang, J Y

    2015-12-14

    The interleukin-18 (IL-18) gene -607 C/A polymorphism has been reported to be associated with gastrointestinal cancer, but there are conflicting results from previous studies on said topic. Therefore, the aim of this meta-analysis is to derive a more precise estimation of the association between the -607 C/A polymorphism in the IL-18 gene and gastrointestinal cancer risk. Literature searches of PubMed, Google Scholar, and Web of Science databases were carried out in 2015. Five studies were assessed with a total of 1618 cases and 1155 healthy controls. When results from all eligible studies were pooled into the meta-analysis, we found significant association between the IL-18 gene -607 C/A polymorphism and gastrointestinal cancer risk (CC vs AA: OR = 0.93, 95%CI = 0.72- 1.20; CC vs CA: OR = 0.76, 95%CI = 0.62-0.92; dominant model: OR = 1.25, 95%CI = 1.03-1.50; recessive model: OR = 1.09, 95%CI = 0.87-1.37). In the subgroup analysis, significant associations between the -607 C/A polymorphism and gastrointestinal cancer risk were found in esophageal cancer. However, this polymorphism did not appear to have any influence on gastric cancer and colorectal cancer susceptibility. In conclusion, this meta-analysis suggests that the -607 C/A polymorphism in the IL-18 gene may be associated with susceptibility to esophageal cancer. Further studies with large sample sizes are needed to confirm these conclusions.

  2. Association between CYP1A2 and CYP1B1 Polymorphisms and Colorectal Cancer Risk: A Meta-Analysis

    PubMed Central

    Liu, Zhi-Zhong; Xie, Jian-Jun; Wang, Wei; Du, Ya-Ping; Chen, Yu; Si, Hui-Qiang; Liu, Qing; Wu, Li-Xia; Wei, Wu

    2014-01-01

    Background The previous published data on the association between CYP1A2*F (rs762551), CYP1B1 Leu432Val (rs1056836), Asn453Ser (rs180040), and Arg48Gly (rs10012) polymorphisms and colorectal cancer risk remained controversial. Methodology/Principal Findings The purpose of this study is to evaluate the role of CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly genotypes in colorectal cancer susceptibility. We performed a meta-analysis on all the eligible studies that provided 5,817 cases and 6,544 controls for CYP1A2*F (from 13 studies), 9219 cases and 10406 controls for CYP1B1 Leu432Val (from 12 studies), 6840 cases and 7761 controls for CYP1B1 Asn453Ser (from 8 studies), and 4302 cases and 4791 controls for CYP1B1Arg48Gly (from 6 studies). Overall, no significant association was found between CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly and colorectal cancer risk when all the eligible studies were pooled into the meta-analysis. And in the subgroup by ethnicity and source of controls, no evidence of significant association was observed in any subgroup analysis. Conclusions/Significance In summary, this meta-analysis indicates that CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly polymorphisms do not support an association with colorectal cancer, and further studies are needed to investigate the association. In addition, our work also points out the importance of new studies for CYP1A2*F polymorphism in Asians, because high heterogeneity was found (dominant model: I2 = 81.3%; heterozygote model: I2 = 79.0). PMID:25115775

  3. 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.

  4. Association of CYP1B1 gene polymorphisms with susceptibility to endometrial cancer: a meta-analysis.

    PubMed

    Wang, Fang; Zou, Yan-Feng; Sun, Guo-Ping; Su, Hong; Huang, Fen

    2011-03-01

    The objective of this meta-analysis was to quantitatively summarize the association of CYP1B1 gene polymorphisms and endometrial cancer risk. Data were collected from the following electronic databases: PubMed,Elsevier Science Direct, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure and Wanfang, with the last report up to June 2010. Meta-analysis was conducted in a fixed/random effect model. Out of the 715 papers retrieved 12 studies (3605 cases and 5692 controls) on the association of CYP1B1 gene polymorphisms with endometrial cancer risk in different ethnic groups were identified. Meta-analysis was performed for CYP1B1 gene polymorphisms: R48G (C/G, five studies), L432V (C/G, 12 studies), N453S (A/G, four studies), and A119S (G/T, five studies). We did not detect any association of CYP1B1 gene A119S polymorphism with endometrial cancer. An association of CYP1B1 gene R48G polymorphism with endometrial cancer was found [GG vs. GC+CC: odds ratio (OR)=0.55, 95% confidence interval (CI): 0.42-0.73, P<0.0001; GG vs. CC: OR=0.46, 95% CI: 0.23-0.91, P=0.03]. We found that CYP1B1 gene L432V polymorphism was associated with a significantly increased risk of endometrial cancer (G vs. C: OR=1.23, 95% CI: 1.06-1.43, P=0.007; GC+GG vs. CC:OR=1.24, 95% CI: 1.08-1.43, P=0.003; GC vs. CC: OR=1.16, 95% CI: 1.04-1.29, P=0.009). Moreover, we detected the association of CYP1B1 gene N453S polymorphism with endometrial cancer (G vs. A: OR=0.82,95% CI: 0.72-0.94, P=0.005; GA vs. AA: OR=0.81, 95% CI: 0.69-0.95, P=0.01). In conclusion, this meta-analysis provides strong evidence that CYP1B1 gene R48G, L432V, and N453S polymorphisms are associated with endometrial cancer risk, but not A119S.

  5. The Association of SNAP25 Gene Polymorphisms in Attention Deficit/Hyperactivity Disorder: a Systematic Review and Meta-Analysis.

    PubMed

    Liu, Yun-Sheng; Dai, Xuan; Wu, Wei; Yuan, Fang-Fen; Gu, Xue; Chen, Jian-Guo; Zhu, Ling-Qiang; Wu, Jing

    2017-04-01

    Attention deficit/hyperactivity disorder (ADHD) is one of the most highly heritable psychiatric disorders in childhood. The risk gene mutation accounts for about 60 to 90 % cases. Synaptosomal-associated protein of 25 kDa (SNAP-25) is a presynaptic plasma membrane protein which is expressed highly and specifically in the neuronal cells. A number of evidences have suggested the role of SNAP-25 in the etiology of ADHD. Notably, the animal model of coloboma mouse mutant bears a ∼2-cM deletion encompassing genes including SNAP25 and displays spontaneous hyperkinetic behavior. Previous investigators have reported association between SNPs in SNAP25 and ADHD, and controversial results were observed. In this study, we analyzed the possible association between six polymorphisms (rs3746544, rs363006, rs1051312, rs8636, rs362549, and rs362998) of SNAP25 and ADHD in a pooled sample of ten family-based studies and four case-control studies by using meta-analysis. The combined analysis results were significant only for rs3746544 (P = 0.010) with mild association (odds ratio (OR) = 1.14). And, the meta-analysis data for rs8636, rs362549, and rs362998 are the first time to be reported; however, no positive association was detected. In conclusion, we report some evidence supporting the association of SNAP25 to ADHD. Future research should emphasize genome-wide association studies in more specific subgroups and larger independent samples.

  6. The Association between RAD23B Ala249Val Polymorphism and Cancer Susceptibility: Evidence from a Meta-Analysis

    PubMed Central

    Ying, Xiaojiang; Song, Junmin; Zhang, Ruoxin; Li, Zhen; Chen, Hongliang; Ye, Pingjiang; Shen, Yi; Pan, Weihuo; Chen, Zhiliang

    2014-01-01

    Background A number of studies have investigated associations of genetic variation in RAD23B Ala249Val (rs1805329 C>T) with cancer susceptibility; however, the findings are inconsistent. We performed a meta-analysis to acquire a more precise estimation of the relationship. Method We searched literatures from PubMed, Embase and Web of Science. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association between Ala249Val polymorphism and cancer risk. Results A total of 23 studies consisting of 10837 cases and 13971 controls were included in this meta-analysis. Overall, no significant associations were found between RAD23B Ala249Val polymorphism and cancer risk (Val/Val vs. Ala/Ala: OR = 0.97, 95% CI = 0.75–1.25; Ala/Val vs. Ala/Ala: OR = 1.08, 95% CI = 0.96–1.22; recessive model: OR = 0.93, 95% CI = 0.76–1.14 and dominant model: OR = 1.07, 95% CI = 0.94–1.20). We did not find any significant associations in the further stratification analyses by cancer type, ethnicity and source of control. Conclusions Despite some limitations, this meta-analysis indicates that it is unlikely that the RAD23B 249Val/Val polymorphism may contribute to the individual susceptibility to cancer risk. However, further advanced designed studies with larger sample size and different ethnicities should be conducted to confirm our results. PMID:24643114

  7. 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.

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

    PubMed Central

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

    2017-01-01

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

  9. Association between shortened telomere length and systemic lupus erythematosus: a meta-analysis.

    PubMed

    Lee, Y H; Jung, J H; Seo, Y H; Kim, J-H; Choi, S J; Ji, J D; Song, G G

    2017-03-01

    Objective We aimed to evaluate the relationship between telomere length and systemic lupus erythematosus (SLE). Methods PUBMED and EMBASE databases were searched; meta-analyses were performed comparing telomere length in SLE patients and healthy controls, and on SLE patients in subgroups based on ethnicity, sample type, assay method and data type. Results Eight studies including 472 SLE patients and 365 controls were ultimately selected which showed that telomere length was significantly shorter in the SLE group than in the control group (standardized mean difference (SMD) = -0.835, 95% confidence interval (CI) = -1.291 to -0.380, p = 3.3 × 10(-4)). Stratification by ethnicity showed significantly shortened telomere length in the SLE group in Caucasian, Asian and mixed populations (SMD = -0.455, 95% CI = -0.763 to -0.147, p = 0.004; SMD = -0.887, 95% CI = -1.261 to -0.513, p = 3.4 × 10(-4); SMD = -0.535, 95% CI = -0.923 to -0.147, p = 0.007; respectively). Furthermore, telomere length was significantly shorter in the SLE group than in the control group in whole blood and peripheral blood mononuclear cell groups (SMD = -0.361, 95% CI = -0.553 to -0.169, p = 2.3 × 10(-4); SMD = -1.546, 95% CI = -2.583 to -0.510, p = 0.003; respectively); a similar trend was observed in leukocyte groups (SMD = -0.699, 95% CI = -1.511 to -0.114, p = 0.092). Meta-analyses based on assay method or data type revealed similar associations. Conclusions Our meta-analysis demonstrated that telomere length was significantly shorter in patients with SLE, regardless of ethnicity, sample type or assay method evaluated.

  10. Sequential sentinel SNP Regional Association Plots (SSS-RAP): an approach for testing independence of SNP association signals using meta-analysis data.

    PubMed

    Zheng, Jie; Gaunt, Tom R; Day, Ian N M

    2013-01-01

    Genome-Wide Association Studies (GWAS) frequently incorporate meta-analysis within their framework. However, conditional analysis of individual-level data, which is an established approach for fine mapping of causal sites, is often precluded where only group-level summary data are available for analysis. Here, we present a numerical and graphical approach, "sequential sentinel SNP regional association plot" (SSS-RAP), which estimates regression coefficients (beta) with their standard errors using the meta-analysis summary results directly. Under an additive model, typical for genes with small effect, the effect for a sentinel SNP can be transformed to the predicted effect for a possibly dependent SNP through a 2×2 2-SNP haplotypes table. The approach assumes Hardy-Weinberg equilibrium for test SNPs. SSS-RAP is available as a Web-tool (http://apps.biocompute.org.uk/sssrap/sssrap.cgi). To develop and illustrate SSS-RAP we analyzed lipid and ECG traits data from the British Women's Heart and Health Study (BWHHS), evaluated a meta-analysis for ECG trait and presented several simulations. We compared results with existing approaches such as model selection methods and conditional analysis. Generally findings were consistent. SSS-RAP represents a tool for testing independence of SNP association signals using meta-analysis data, and is also a convenient approach based on biological principles for fine mapping in group level summary data.

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

    PubMed Central

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

    2017-01-01

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

  12. 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

  13. Are proton pump inhibitors associated with the development of community-acquired pneumonia? A meta-analysis.

    PubMed

    Giuliano, Christopher; Wilhelm, Sheila M; Kale-Pradhan, Pramodini B

    2012-05-01

    This study was presented at the American College of Chest Physicians meeting in Pittsburgh (PA, USA) in October 2011. The study objective was to evaluate the association of proton pump inhibitors (PPIs) and community-acquired pneumonia (CAP). The design was a meta-analysis of nine case-controlled and cohort studies. 120,863 pneumonia cases from 1987 to 2006 were included in the meta-analysis. PubMed and Ovid Medline were searched from inception through May 2011 by two investigators independently using keywords: PPI, pneumonia, CAP, anti-ulcer, antacid, omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole. This meta-analysis only included case-controlled and cohort studies that were published in full in English and evaluated PPI use and CAP incidence. Studies were excluded if they included the following patients: pediatric, Helicobacter pylori treatment and critically ill. Bibliographies of recent review articles and systematic reviews were hand-searched. Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Two investigators independently extracted data into standardized data collection forms that were confirmed by a third investigator. Data were analyzed based on current use of PPIs, duration of PPI use (<30 days or >180 days) and PPI dose (high vs low). Overall association of PPI and CAP was analyzed using the random effects model (Comprehensive Meta analysis(®) Version 2.0). Nine studies met all criteria for the primary outcome. Newcastle-Ottawa Quality Assessment Scale scores ranged from 4 to 8 out of 9. Current use of PPIs (odds ratio [OR]: 1.39; 95% CI: 1.09-1.76), PPI use <30 days (OR: 1.65; 95% CI: 1.25-2.19), PPI high dose (OR: 1.50; 95% CI: 1.33-1.68) and PPI low dose (OR: 1.17; 95% CI: 1.11-1.24) were significantly associated with CAP. There was no association between CAP and PPI use >180 days (OR: 1.10; 95% CI: 1.00-1.21). In conclusion, patients currently receiving PPIs, particularly <30 days or high dose

  14. Associations between dopamine D2 receptor gene polymorphisms and schizophrenia risk: a PRISMA compliant meta-analysis

    PubMed Central

    He, Hairong; Wu, Huanhuan; Yang, Lihong; Gao, Fan; Fan, Yajuan; Feng, Junqin; Ma, Xiancang

    2016-01-01

    Objective To determine the relationships between dopamine D2 receptor gene polymorphisms and the risk of schizophrenia using meta-analysis. Method The PubMed, Embase, and China National Knowledge Infrastructure databases were searched to identify relevant literature published up to February 2016. The allele contrast model was used. Stata software was used for statistical analysis, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated to evaluate the associations between dopamine D2 receptor gene polymorphisms and the risk of schizophrenia. Meta-regression and publication bias, trim-and-fill, subgroup, sensitivity, cumulative, and fail-safe number analyses were also performed. Results This meta-analysis included 81 studies. The rs1801028 and rs1799732 were associated with schizophrenia risk among Asians (P=0.04, OR =1.25, 95% CI =1.01–1.55; P<0.01, OR =0.76, 95% CI =0.63–0.92, respectively), while the rs6277 was associated with schizophrenia risk in Caucasians (P<0.01, OR=0.72, 95% CI =0.66–0.79). The rs1800497 was also associated with schizophrenia risk in population-based controls (P<0.01, OR =0.84, 95% CI =0.72–0.97). The rs6275, rs1079597, and rs1800498 were not associated with schizophrenia risk. In addition, meta-regression indicated that the controls may be sources of heterogeneity for the rs1801028 single-nucleotide polymorphism (SNP), while ethnicity may be sources of heterogeneity for the rs6277 SNP. Publication bias was significant for the rs1801028 SNP, and this result changed after the publication bias was adjusted using the trim-and-fill method. Conclusion This meta-analysis demonstrated that the rs1801028 may be a risk factor for susceptibility to schizophrenia among Asians, while the rs1799732 may be a protective factor for that population. Large-sample studies are necessary to verify the results of this meta-analysis. PMID:28003749

  15. Association of the variants in the PPARG gene and serum lipid levels: a meta-analysis of 74 studies

    PubMed Central

    Li, Qing; Chen, Rong; Bie, Lizhan; Zhao, Dandan; Huang, Chunkai; Hong, Jiang

    2015-01-01

    Considerable studies have been carried out to investigate the relationship between the polymorphisms of PPARG (Pro12Ala, C161T and C1431T) and serum lipid levels, but the results were inconclusive. Hence, we conducted a meta-analysis to clarify the association. MEDLINE, EMBASE and the Cochrane Library databases were searched systematically. The subgroup analysis was performed based on ethnicity. Seventy-four studies with 54,953 subjects were included in this meta-analysis. In Pro12Ala, the group with the ‘PP’ (C/C genotype) genotype group had lower levels of total cholesterol (TC) (mean difference, MD: −0.02, P < 0.00001; I2 = 28%), low-density lipoprotein cholesterol (LDL-C) (MD: −0.02, P < 0.00001; I2 = 30%) and higher levels of triglyceride (TG) (MD: 0.06, P < 0.00001; I2 = 30%) than the combined ‘PA+AA’ (PA = C/G genotype, AA = G/G genotype) genotype group in Asian population, and the group with the ‘PP’ genotype had higher levels of TG (MD: 0.07, P < 0.02; I2 = 67%) than the combined ‘PA+AA’ genotype group in non-Asian population. No statistically significant differences in the levels of TC, TG, high-density lipoprotein cholesterol, LDL-C were detected between different genotypes in C161T(Asian or non-Asian) and C1431T(Asian) polymorphisms. This meta-analysis was a renewed and confirmed study to assess the association between PPARG polymorphisms and serum lipid levels in Asian and non-Asian populations. There is a prominent association between Pro12Ala polymorphism and the levels of TC, LDL-C and TG in Asian population. No statistically significant differences in serum lipid levels were detected between different genotypes in C161T and C1431T polymorphisms. PMID:25265984

  16. Association between pretreatment Glasgow prognostic score and gastric cancer survival and clinicopathological features: a meta-analysis

    PubMed Central

    Zhang, Chun-Xiao; Wang, Shu-Yi; Chen, Shuang-Qian; Yang, Shuai-Long; Wan, Lu; Xiong, Bin

    2016-01-01

    Background Glasgow prognostic score (GPS) is widely known as a systemic inflammatory-based marker. The relationship between pretreatment GPS and gastric cancer (GC) survival and clinicopathological features remains controversial. The aim of the study was to conduct a meta-analysis of published studies to evaluate the association between pretreatment GPS and survival and clinicopathological features in GC patients. Methods We searched PubMed, Embase, MEDLINE, and BioMed databases for relevant studies. Combined analyses were used to assess the association between pretreatment GPS and overall survival, disease-free survival, and clinicopathological parameters by Stata Version 12.0. Results A total of 14 studies were included in this meta-analysis, including 5,579 GC patients. The results indicated that pretreatment high GPS (HGPS) predicted poor overall survival (hazard ratio =1.51, 95% CI: 1.37–1.66, P<0.01) and disease-free survival (hazard ratio =1.45, 95% CI: 1.26–1.68, P<0.01) in GC patients. Pretreatment HGPS was also significantly associated with advanced tumor–node–metastasis stage (odds ratio [OR] =3.09, 95% CI: 2.11–4.53, P<0.01), lymph node metastasis (OR =4.60, 95% CI: 3.23–6.56, P<0.01), lymphatic invasion (OR =3.04, 95% CI: 2.00–4.62, P<0.01), and venous invasion (OR =3.56, 95% CI: 1.81–6.99, P<0.01). Conclusion Our meta-analysis indicated that pretreatment HGPS could be a predicative factor of poor survival outcome and clinicopathological features for GC patients. PMID:27390529

  17. Association between physical activity and all cancer mortality: Dose-response meta-analysis of cohort studies.

    PubMed

    Li, Yingjun; Gu, Mengjia; Jing, Fangyuan; Cai, Shaofang; Bao, Chengzhen; Wang, Jianbing; Jin, Mingjuan; Chen, Kun

    2016-02-15

    The relationship between physical activity (PA) before cancer diagnosis and all cancer mortality among the general population is not well defined because of inconsistent results from published studies. Thus, the lack of a meta-analysis that addresses that issue prompted the current report. We conducted a literature search of PubMed and Web of Science to identify all relevant epidemiological studies published before February 28, 2015. We performed categorical and dose-response meta-analyses to evaluate and quantify the association between pre-diagnosis PA and all cancer mortality. A total of 32 prospective cohort studies involving 59,362 cancer deaths were included in this meta-analysis. The pooled relative risks (RRs) of all cancer mortality were 0.80 [95% confidence interval (CI) = 0.76-0.85)] for highest versus lowest PA group and 0.85 (95% CI = 0.82-0.88) for PA versus non/occasional PA group. Dose-response analysis showed that the increment in pre-diagnosis PA level was associated with a decreased risk of cancer death continuously. Moreover, an increment of 10 MET-h/week was related to a 7% lower risk for all cancer mortality (RR = 0.93, 95% CI = 0.91-0.95). In conclusion, the present meta-analysis provides evidence of an inverse association between pre-diagnosis PA and all cancer mortality among the general population. High-quality epidemiological studies that employ standardized PA assessments and unified definitions of PA levels should be developed in future.

  18. Associations of the Baltic Sea diet with cardiometabolic risk factors--a meta-analysis of three Finnish studies.

    PubMed

    Kanerva, Noora; Kaartinen, Niina E; Rissanen, Harri; Knekt, Paul; Eriksson, Johan G; Sääksjärvi, Katri; Sundvall, Jouko; Männistö, Satu

    2014-08-28

    Dyslipidaemia, hypertension and low-grade inflammation increase the risk of CVD. In the present meta-analysis, we examined whether adherence to a healthy Nordic diet, also called the Baltic Sea diet, may associate with a lower risk of these cardiometabolic risk factors. In 2001-2007, three cross-sectional Finnish studies were conducted: the Dietary, Lifestyle and Genetic Determinants of Obesity and Metabolic Syndrome study (n 4776); Health 2000 Survey (n 5180); Helsinki Birth Cohort Study (n 1972). The following parameters were assessed in these three studies: blood pressure, total, HDL- and LDL-cholesterol, TAG and high-sensitivity C-reactive protein (hs-CRP); a validated FFQ was used to assess the participants' dietary intakes. The Baltic Sea Diet Score (BSDS) was developed based on the healthy Nordic diet. All studies assessed confounding variables, such as physical activity and BMI, based on standardised questionnaires and measurements. The random-effects meta-analysis provided summary estimates for OR and 95 % CI by the BSDS quintiles. In the meta-analysis, the risk of elevated hs-CRP concentration was lower among men (OR 0·58, 95 % CI 0·43, 0·78) and women (OR 0·73, 95 % CI 0·58, 0·91) in the highest BSDS quintile than among those in the lowest BSDS quintile. In contrast, the risk of lowered HDL-cholesterol concentration was higher among women (OR 1·67, 95 % CI 1·12, 2·48) in the highest BSDS quintile than among those in the lowest BSDS quintile. However, no other associations were found. In conclusion, the associations between the adherence to the healthy Nordic diet and cardiometabolic risk factors are equivocal. Longitudinal studies are needed to further examine this hypothesis.

  19. 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

  20. Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking

    PubMed Central

    Terracciano, A; Esko, T; Sutin, A R; de Moor, M H M; Meirelles, O; Zhu, G; Tanaka, T; Giegling, I; Nutile, T; Realo, A; Allik, J; Hansell, N K; Wright, M J; Montgomery, G W; Willemsen, G; Hottenga, J-J; Friedl, M; Ruggiero, D; Sorice, R; Sanna, S; Cannas, A; Räikkönen, K; Widen, E; Palotie, A; Eriksson, J G; Cucca, F; Krueger, R F; Lahti, J; Luciano, M; Smoller, J W; van Duijn, C M; Abecasis, G R; Boomsma, D I; Ciullo, M; Costa, P T; Ferrucci, L; Martin, N G; Metspalu, A; Rujescu, D; Schlessinger, D; Uda, M

    2011-01-01

    The tendency to seek stimulating activities and intense sensations define excitement-seeking, a personality trait akin to some aspects of sensation-seeking. This trait is a central feature of extraversion and is a component of the multifaceted impulsivity construct. Those who score high on measures of excitement-seeking are more likely to smoke, use other drugs, gamble, drive recklessly, have unsafe/unprotected sex and engage in other risky behaviors of clinical and social relevance. To identify common genetic variants associated with the Excitement-Seeking scale of the Revised NEO Personality Inventory, we performed genome-wide association studies in six samples of European ancestry (N=7860), and combined the results in a meta-analysis. We identified a genome-wide significant association between the Excitement-Seeking scale and rs7600563 (P=2 × 10−8). This single-nucleotide polymorphism maps within the catenin cadherin-associated protein, alpha 2 (CTNNA2) gene, which encodes for a brain-expressed α-catenin critical for synaptic contact. The effect of rs7600563 was in the same direction in all six samples, but did not replicate in additional samples (N=5105). The results provide insight into the genetics of excitement-seeking and risk-taking, and are relevant to hyperactivity, substance use, antisocial and bipolar disorders. PMID:22833195

  1. Sequential priming measures of implicit social cognition: a meta-analysis of associations with behavior and explicit attitudes.

    PubMed

    Cameron, C Daryl; Brown-Iannuzzi, Jazmin L; Payne, B Keith

    2012-11-01

    In a comprehensive meta-analysis of 167 studies, the authors found that sequential priming tasks were significantly associated with behavioral measures (r = .28) and with explicit attitude measures (r = .20). Priming tasks continued to predict behavior after controlling for the effects of explicit attitudes. These results generalized across a variety of study domains and methodological variations. Within-study moderator analyses revealed that priming tasks have good specificity, only predicting behavior and explicit measures under theoretically expected conditions. Together, these results indicate that sequential priming-one of the earliest methods of investigating implicit social cognition--continues to be a valid tool for the psychological scientist.

  2. Lack of association between EPHX1 polymorphism and esophageal cancer risk: evidence from meta-analysis.

    PubMed

    Yan, Y L; Chen, X; Liang, H J; Wang, J; Li, T J; Li, R L; Li, S; Qin, X

    2015-01-01

    The microsomal epoxide hydrolase 1 (EPHX1) Tyr113His and His139Arg polymorphisms have been reported to be associated with esophageal cancer (EC) risk, yet the results of these previous results have been inconsistent or controversial. The objective of this study was to explore whether the EPHX1 Tyr113His and His139Arg polymorphisms confer risk to EC. The relevant studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct, and Chinese Biomedical Literature Database until May 2013. The association between the EPHX1 Tyr113His and His139Arg polymorphisms and EC risk was pooled by odds ratios (ORs) together with their 95% confidence intervals (95%CIs). A total of eight case-control studies with 1163 EC patients and 1868 controls (seven studies for both Tyr113His and His139Arg polymorphisms, one study only for Tyr113His polymorphism) were eventually identified. We found no association between EPHX1 Tyr113His and His139Arg polymorphisms and EC risk in overall population (For Tyr113His: His vs. Tyr: OR = 1.05, 95%CI = 0.95-1.15, P = 0.379; His/His vs. Tyr/Tyr: OR = 1.04, 95%CI = 0.88-1.22, P = 0.208; His/Tyr vs. Tyr/Tyr: OR = 0.96, 95%CI = 0.80-1.15, P = 0.577; His/His vs. His/Tyr + Tyr/Tyr: OR = 1.10, 95%CI = 0.96-1.26, P = 0.164; His/His + His/Tyr vs. Tyr/Tyr: OR = 1.01, 95%CI = 0.90-1.12, P = 0.543. For His139Arg: Arg vs. His: OR = 1.04, 95%CI = 0.94-1.14, P = 0.465; Arg/Arg vs. His/His: OR = 1.06, 95%CI = 0.91-1.24, P = 0.470; Arg/His vs. His/His: OR = 1.03, 95%CI = 0.91-1.16, P = 0.673; Arg/Arg vs. Arg/His + His/His: OR = 1.04, 95%CI = 0.85-1.27, P = 0.708; Arg/Arg + Arg/His vs. His/His: OR = 1.02, 95%CI = 0.93-1.13, P = 0.617). In subgroup analysis based on ethnicity, significant association has been found in neither EPHX1 Tyr113His nor His139Arg polymorphism. The current meta-analysis

  3. 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

  4. Association of depressive symptoms and suicidal ideation among university students in China: A systematic review and meta-analysis.

    PubMed

    Wang, Yu-Hang; Shi, Zhou-Ting; Luo, Qian-Ying

    2017-03-01

    The aim of this study was to investigate whether depressive symptoms are associated with suicidal ideation among university students in China.Five Chinese and English electronic databases (EBSCO, PubMed, Chinese Web of Knowledge, Wanfang, and Weipu) were searched to identify relevant studies. Cross-sectional studies published from 2000 to 2016 reporting about the association between depressive symptoms and suicidal ideation among university students in China were used for meta-analysis to approximate the overall association between depression and suicidal ideation among university students in mainland China. StatsDirect 3 was used for meta-analysis of included literatures.Of 513 initially identified references, 44 studies were selected, including 88,431 participants with depressive symptoms. The combined odd ratio of the relationship was 2.174 (95% confidence interval: 2.027-2.333; P < 0.0001).There exists a moderate association between depressive symptoms and suicidal ideation among university students in China, and depressive symptoms contribute to the development of suicidal ideation. In particular, university students from western regions of China, from nonmedical background, should be provided more psychological and clinical assistance.

  5. Association between VEGF -634G/C polymorphism and susceptibility to autoimmune diseases: a meta-analysis.

    PubMed

    Chen, Haikui; Zhang, Tianyun; Gong, Bolin; Cao, Xiaohong

    2015-03-10

    The role of VEGF -634G/C polymorphism has been involved in the investigations of susceptibility to autoimmune diseases, but the conclusion remains controversial. Here, we have performed a meta-analysis to clarify the relationship between them. All relevant articles updating to August 2013 were searched in PubMed and EMBASE. Crude odds ratios (ORs) with 95% confidence intervals (CIs) based on the available articles were calculated. A total of 24 independent studies associated with autoimmune disease were analyzed in our research. The results show that VEGF -634G/C polymorphism was associated with susceptibility to autoimmune disease in Asian population (C vs. G: OR=0.88, 95% CI: 0.80-0.96, P=0.543; CC vs. GG: OR=0.77, 95% CI: 0.63-0.93, P=0.787; CC+GC vs. GG: OR=0.80, 95% CI: 0.67-0.96, P=0.080 by random effects model). Nevertheless, no significant associations were found in total population or in other stratified groups. In the current meta-analysis, we reveal a significant association between VEGF -634G/C polymorphism and susceptibility to autoimmune diseases in Asian population.

  6. Association between resting heart rate and cardiovascular mortality: evidence from a meta-analysis of prospective studies

    PubMed Central

    Li, Yuechun

    2015-01-01

    The results from published studies on resting heart rate (RHR) and risk of cardiovascular mortality are not consistent. We therefore conducted a meta-analysis to quantitatively summarize the evidence from prospective studies about the association of RHR with risk cardiovascular mortality. Pertinent studies were identified by a search of Pubmed and Web of Knowledge to January 2015. The random effect model was used. Sensitivity analysis and publication bias were conducted. Dose-response relationship was assessed by restricted cubic spline and variance-weighted least squares regression analysis. Twenty prospective articles were included in this meta-analysis. Pooled results suggested that highest RHR level versus lowest levels was significantly associated with the risk of cardiovascular mortality [summary relative risk (RR) = 1.69, 95% CI = 1.42-2.00, I2 = 87.5%]. Subjects with RHR levels of > 80 bites per minute (bpm) had a RR of 1.49 (1.24-1.79) for cardiovascular mortality. The results for subgroups analysis of geographic locations, sex and duration of follow-up are consistent with the overall results. The linear dose-response analysis indicated that an increase in RHR of 10 bpm was statistically significantly associated with a 6% increase in the risk of developing cardiovascular mortality (summary RR = 1.06, 95% CI = 1.04-1.08). Thus, we conclude that elevated RHR was significantly associated with an increased risk of cardiovascular mortality. PMID:26629022

  7. Association between whole grain intake and all-cause mortality: a meta-analysis of cohort studies

    PubMed Central

    Yang, Yang; Zhang, Qing-Li; Zheng, Jia-Li; Xiang, Yong-Bing

    2016-01-01

    Some observational studies have examined the association between dietary whole grain intake and all-cause mortality, but the results were inconclusive. We therefore conducted a meta-analysis to summarize the evidence from cohort studies regarding the association between whole grain intake and all-cause mortality. Pertinent studies were identified by searching PubMed, Embase and Web of Knowledge, up to February 28, 2016. Study-specific estimates were combined using random-effects models. Eleven prospective cohort studies involving 101,282 deaths and 843,749 participants were included in this meta-analysis. The pooled relative risk of all-cause mortality for the highest category of whole grain intake versus lowest category was 0.82 (95% confidence interval: 0.78, 0.87). There was a 7% reduction in risk associated with each 1 serving/day increase in whole grain intake (relative risk = 0.93; 95% confidence interval: 0.89, 0.97). No publication bias was found. This analysis indicates that higher intake of whole grain is associated with a reduced risk of all-cause mortality. The findings support current recommendations for increasing whole grain consumption to promote health and overall longevity. PMID:27566558

  8. Association between mobile phone use and semen quality: a systemic review and meta-analysis.

    PubMed

    Liu, K; Li, Y; Zhang, G; Liu, J; Cao, J; Ao, L; Zhang, S

    2014-07-01

    Possible hazardous health effects of radiofrequency electromagnetic radiations emitted from mobile phone on the reproductive system have raised public concern in recent years. This systemic review and meta-analysis was prepared following standard procedures of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and checklist. Relevant studies published up to May 2013 were identified from five major international and Chinese literature databases: Medline/PubMed, EMBASE, CNKI, the VIP database and the Cochrane Central Register of Controlled Trials in the Cochrane Library. Eighteen studies with 3947 men and 186 rats were included in the systemic review, of which 12 studies (four human studies, four in vitro studies and four animal studies) with 1533 men and 97 rats were used in the meta-analyses. Systemic review showed that results of most of the human studies and in vitro laboratory studies indicated mobile phone use or radiofrequency exposure had negative effects on the various semen parameters studied. However, meta-analysis indicated that mobile phone use had no adverse effects on semen parameters in human studies. In the in vitro studies, meta-analysis indicated that radiofrequency radiation had detrimental effect on sperm motility and viability in vitro [pooled mean difference (MDs) (95% CI): -4.11 (-8.08, -0.13), -3.82 (-7.00, -0.65) for sperm motility and viability respectively]. As for animal studies, radiofrequency exposure had harmful effects on sperm concentration and motility [pooled MDs (95% CI): -8.75 (-17.37, -0.12), -17.72 (-32.79, -2.65) for sperm concentration and motility respectively]. Evidence from current studies suggests potential harmful effects of mobile phone use on semen parameters. A further multicentred and standardized study is needed to assess the risk of mobile phone use on the reproductive system.

  9. 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.

  10. Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies.

    PubMed

    Rivadeneira, Fernando; Styrkársdottir, Unnur; Estrada, Karol; Halldórsson, Bjarni V; Hsu, Yi-Hsiang; Richards, J Brent; Zillikens, M Carola; Kavvoura, Fotini K; Amin, Najaf; Aulchenko, Yurii S; Cupples, L Adrienne; Deloukas, Panagiotis; Demissie, Serkalem; Grundberg, Elin; Hofman, Albert; Kong, Augustine; Karasik, David; van Meurs, Joyce B; Oostra, Ben; Pastinen, Tomi; Pols, Huibert A P; Sigurdsson, Gunnar; Soranzo, Nicole; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Williams, Frances M K; Wilson, Scott G; Zhou, Yanhua; Ralston, Stuart H; van Duijn, Cornelia M; Spector, Timothy; Kiel, Douglas P; Stefansson, Kari; Ioannidis, John P A; Uitterlinden, André G

    2009-11-01

    Bone mineral density (BMD) is a heritable complex trait used in the clinical diagnosis of osteoporosis and the assessment of fracture risk. We performed meta-analysis of five genome-wide association studies of femoral neck and lumbar spine BMD in 19,195 subjects of Northern European descent. We identified 20 BMD loci that reached genome-wide significance (GWS; P < 5 x 10(-8)), of which 13 map to regions not previously associated with this trait: 1p31.3 (GPR177), 2p21 (SPTBN1), 3p22 (CTNNB1), 4q21.1 (MEPE), 5q14 (MEF2C), 7p14 (STARD3NL), 7q21.3 (FLJ42280), 11p11.2 (LRP4, ARHGAP1, F2), 11p14.1 (DCDC5), 11p15 (SOX6), 16q24 (FOXL1), 17q21 (HDAC5) and 17q12 (CRHR1). The meta-analysis also confirmed at GWS level seven known BMD loci on 1p36 (ZBTB40), 6q25 (ESR1), 8q24 (TNFRSF11B), 11q13.4 (LRP5), 12q13 (SP7), 13q14 (TNFSF11) and 18q21 (TNFRSF11A). The many SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism and highlight the complex genetic architecture that underlies osteoporosis and variation in BMD.

  11. 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

  12. Association between DAZL polymorphisms and susceptibility to male infertility: systematic review with meta-analysis and trial sequential analysis

    PubMed Central

    Zhang, Simin; Tang, Qiuqin; Wu, Wei; Yuan, Beilei; Lu, Chuncheng; Xia, Yankai; Ding, Hongjuan; Hu, Lingqing; Chen, Daozhen; Sha, Jiahao; Wang, Xinru

    2014-01-01

    Several studies have investigated the association between polymorphisms in the Deleted in AZoospermia-Like (DAZL) gene and male infertility risk, but with inconsistent results. We aimed to derive a more precise estimation of the relationship, therefore a meta-analysis was performed. A total of 13 case-control studies, including 2556 cases and 1997 controls, were selected. Two polymorphisms in DAZL were investigated, namely T12A (Thr12 → Ala) and T54A (Thr54 → Ala). Our meta-analysis showed that A > G is a risk factor for male infertility (P = 0.047, OR = 1.262, 95%CI = 1.003–1.587). However, when using trial sequential analysis (TSA) to confirm, we found that A > G risk effect turned out to be false positive. In addition, significant association was found between the T54A polymorphism and male infertility under co-dominant model (AG vs. AA: OR = 4.364, 95%CI = 2.207–8.630, P < 0.001) and dominant model (OR = 4.584, 95%CI = 2.320–9.058, P < 0.001). Stratified analysis showed that significantly strong association between T54A polymorphism and male infertility was present only in Asians, but not in Caucasians. Further studies of T12A and T54A with their biological functions are needed to understand the role of these polymorphisms in the development of male infertility. PMID:24717865

  13. Association between dietary vitamin C intake and risk of esophageal cancer: A dose-response meta-analysis.

    PubMed

    Bo, Yacong; Lu, Yan; Zhao, Yan; Zhao, Erjiang; Yuan, Ling; Lu, Weiquan; Cui, Lingling; Lu, Quanjun

    2016-04-15

    While several epidemiological studies have investigated the association between vitamin C and risk of esophageal cancer, the results remain inconsistent. In the present study, a meta-analysis was conducted to assess the impact of dietary vitamin C intake on esophageal cancer risk. Online databases were searched up to March 29, 2015, for studies on the association between dietary vitamin C intake and esophageal cancer risk. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Dose-response analyses were performed using the method of restricted cubic splines with four knots at percentiles of 5, 35, 65 and 95% of the distribution. Publication bias was estimated using Egger's tests and funnel plots. In all, 15 articles were included in this meta-analysis, including 20 studies, containing 7063 controls and 3955 cases of esophageal cancer. By comparing the highest vs. the lowest categories of vitamin C intake, we found that vitamin C was inversely associated with the risk of esophageal cancer [overall OR = 0.58, 95% CI = 0.49-0.68, I(2) = 56%]. A linear dose-response relationship was found. With an increase in dietary vitamin C intake of 50 mg/day, the risk of esophageal cancer statistically decreased by 13% (OR = 0.87, 95% CI = 0.80-0.93, p(linearity) = 0.0002). In conclusion, our analysis suggested that the higher intake of dietary vitamin C might have a protective effect against esophageal cancer.

  14. Association between Vascular Endothelial Growth Factor Polymorphisms and Age-Related Macular Degeneration: An Updated Meta-Analysis

    PubMed Central

    Maugeri, Andrea

    2016-01-01

    Age-related macular degeneration (AMD) is the most common cause of blindness in elderly people worldwide and the major degenerative disease of the retina that leads to progressive impairment of central vision. Several polymorphisms in different genes have been proposed as factors that increase the disease susceptibility. The aim of the present study is to carry out a systematic review and an updated meta-analysis in order to summarize the current published studies and to evaluate the associations between four common vascular endothelial growth factor (VEGF) polymorphisms (rs833061, rs1413711, rs3025039, and rs2010963) and AMD risk, also stratifying for AMD subtypes and ethnicity. A systematic literature search in the Medline database, using PubMed, was carried out for epidemiological studies, published before June 2016. Associations of VEGF polymorphisms with AMD were estimated by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) based on different models. Twelve articles were included in the analysis. The present meta-analysis constitutes a useful guide for readers to study AMD and adds new evidence to the growing literature on the role of VEGF polymorphisms in the risk of AMD. Significant associations with AMD risk were showed for rs833061, rs1413711, and rs3025039 polymorphisms but not for rs2010963. PMID:27999450

  15. Association between IL-1α rs17561 and IL-1β rs1143634 polymorphisms and periodontitis: a meta-analysis.

    PubMed

    Yin, W T; Pan, Y P; Lin, L

    2016-02-05

    Genetic variations in human interleukin-1 (IL-1) genes are known to be involved in inflammatory disorders. The rs17561 and rs1143634 polymorphisms of IL-1α and IL-1β, respectively, have been increasingly recognized as important regulators in the development of periodontitis. However, the existence of a specific association remains controversial. Therefore, we performed a meta-analysis to explore the relationship between IL-1 polymorphism and periodontitis risk. Based on our inclusion criteria, six case-control studies were used, involving a total of 336 periodontitis cases and 366 healthy controls. Our meta-analysis results showed that the T allele of IL-1α rs17561 is positively associated with periodontitis susceptibility. In addition, carriers of this allele (TC + TT genotypes) demonstrated increased risk of this disease. The IL-1β rs1143634 T allele was also positively connected to periodontitis, with TC + TT genotype carriers being significantly more at risk. These results demonstrate that the IL-1α rs17561 and IL-1β rs1143634 polymorphisms are associated with periodontitis.

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

    PubMed

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

    2012-07-15

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

  17. Adherence to the Mediterranean diet is inversely associated with metabolic syndrome occurrence: a meta-analysis of observational studies.

    PubMed

    Godos, Justyna; Zappalà, Gaetano; Bernardini, Sergio; Giambini, Ilio; Bes-Rastrollo, Maira; Martinez-Gonzalez, Miguel

    2017-03-01

    Diet plays a role in the onset and progression of metabolic disorders, including metabolic syndrome (MetS). We aimed to systematically review and conduct a quantitative meta-analysis of results from observational cross-sectional and prospective cohort studies on adherence to the Mediterranean dietary pattern and risk of MetS. Literature databases including PubMed, SCOPUS and EMBASE were searched from the beginning to May 2016. Eight cross-sectional and four prospective studies were included in this meta-analysis, accounting for a total of 33,847 individuals and 6342 cases of MetS. High adherence to the Mediterranean diet was associated with a risk of MetS (RR: 0.81, 95%CI: 0.71, 0.92). Regarding individual components of the MetS, the inverse associations were significant for waist circumference, blood pressure and low HDL-C levels. In conclusion, adoption of a Mediterranean dietary pattern was associated with lower risk of the MetS and it can be proposed for the primary prevention of the MetS.

  18. Association between selenium intake and the risk of pancreatic cancer: a meta-analysis of observational studies

    PubMed Central

    Wang, Lei; Wang, Jianfeng; Liu, Xudong; Liu, Qian; Zhang, Guozhuan; Liang, Lishuang

    2016-01-01

    Quantification of the association between the intake of selenium and risk of pancreatic cancer is still conflicting. Thus, we conducted a meta-analysis to summarize the evidence from epidemiological studies of selenium intake with the risk of pancreatic cancer. Pertinent studies were identified by a search of PubMed and Web of Knowledge to July 2016. The random-effect model was used. Sensitivity analysis and publication bias were conducted. Data from six studies including 1424 pancreatic cancer cases were used in this meta-analysis. Pooled results suggested that highest selenium intake amount compared with lowest amount was significantly associated with the risk of pancreatic cancer [summary relative risk (RR)=0.659, 95% confidence interval (CI)=0.489–0.889, I2=47.6%]. The associations were significant both in case–control studies [RR=0.618, 95%CI=0.399–0.956, I2=59.1%] and Americas [RR=0.570, 95%CI=0.357–0.909, I2=65.6%]. No publication bias was found. Our analysis suggested that the higher intake of selenium might reduce the risk of pancreatic cancer. PMID:27623938

  19. 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

  20. The Association between Vitamin D Deficiency and Diabetic Retinopathy in Type 2 Diabetes: A Meta-Analysis of Observational Studies

    PubMed Central

    Luo, Bang-An; Gao, Fan; Qin, Lu-Lu

    2017-01-01

    Emerging evidence from in vivo and in vitro studies have shown that vitamin D may play an important role in the development of diabetic retinopathy (DR), but individually published studies showed inconclusive results. The aim of this study was to quantitatively summarize the association between vitamin D and the risk of diabetic retinopathy. We conducted a systematic literature search of Pubmed, Medline, and EMBASE updated in September 2016 with the following keywords: “vitamin D” or “cholecalciferol” or “25-hydroxyvitamin D” or “25(OH)D” in combination with “diabetic retinopathy” or “DR”. Fifteen observational studies involving 17,664 subjects were included. In this meta-analysis, type 2 diabetes patients with vitamin D deficiency (serum 25(OH)D levels <20 ng/mL) experienced a significantly increased risk of DR (odds ratio (OR) = 2.03, 95% confidence intervals (CI): 1.07, 3.86), and an obvious decrease of 1.7 ng/mL (95% CI: −2.72, −0.66) in serum vitamin D was demonstrated in the patients with diabetic retinopathy. Sensitivity analysis showed that exclusion of any single study did not materially alter the overall combined effect. In conclusion, the evidence from this meta-analysis indicates an association between vitamin D deficiency and an increased risk of diabetic retinopathy in type 2 diabetes patients. PMID:28335514

  1. Association between air pollution and sperm quality: A systematic review and meta-analysis.

    PubMed

    Deng, Zibing; Chen, Fei; Zhang, Meixia; Lan, Lan; Qiao, Zhijiao; Cui, Yan; An, Jinghuan; Wang, Nan; Fan, Zhiwei; Zhao, Xing; Li, Xiaosong

    2016-01-01

    Exposure to ambient air pollution has been clearly linked to adverse reproductive outcome and fecundation index, but its effects on male semen quality are still uncertain. In this study, we reviewed information from ten studies to get the qualitative evidence of the influence of the ambient air pollution on sperm quality and collected data from six of the ten studies to conduct meta-analysis. The original studies classified participants into different exposure levels and the highest and lowest expose levels were chosen as high expose and low expose groups, respectively. The random-effect model was used in the meta-analysis with the weight mean difference (WMD) as the measure indicator. The WMDs (95% confidence intervals, CIs) of sperm volume, sperm count, semen concentration, sperm progressive motility, total motility, and normal morphology were 0.09 (-0.04, 0.23), 0.46 (-4.47, 5.39), -8.21 (-20.38, 3.96), -7.76 (-16.26, 0.74), -7.61 (-16.97, 1.74) and -3.40 (-7.42, 0.62), respectively. In conclusion, although the differences are not statistically significant between the two groups, the overall trends and evidence from this review indicate the chronic exposure to ambient pollutants at high level may alter men sperm quality.

  2. Pulmonary arterial hypertension associated with connective tissue disease: meta-analysis of clinical trials

    PubMed Central

    Kuwana, Masataka; Watanabe, Hiroshi; Matsuoka, Nobushige; Sugiyama, Naonobu

    2013-01-01

    Objectives Few studies have focused on pulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTDs). The optimal treatment for CTD-PAH has yet to be established. Design Meta-analysis of the data from evaluations of treatment for PAH generally (19 studies) and CTD-PAH specifically (nine studies) to compare the effects of pulmonary vasodilative PAH agents. MEDLINE, EMBASE and BIOSIS were searched. English-language full-text articles published between January 1990 and August 2012 were eligible. Setting International. Participants Patients with PAH generally (n=3073) and CTD-PAH specifically (n=678). Primary outcome measure Exercise capacity (6 min walk distance, 6 MWD). Results Patients with PAH (all forms) had mean age 32–55 years (women, 61–87%); CTD-PAH patients had mean age 45–55 years (women, 74–95%). Overall estimate of mean change in 6 MWD from baseline (95% CI) for the active treatment group versus the control group in all patients with PAH was 34.6 m (27.4–41.9 m). Pooled mean differences from the results for patients receiving placebo by subgroup of patients receiving phosphodiesterase (PDE)-5 inhibitors, endothelin receptor antagonists (ERAs) and prostacyclin (PGI2) analogues were 22.4–45.5, 39.5–44.2 and 12.4–64.9 m, respectively. Overall estimate of mean difference between changes in 6 MWD in patients with CTD-PAH was 34.2 m (23.3–45.0 m). Pooled mean differences by subgroup of patients receiving PDE-5 inhibitors, ERAs and PGI2 analogues in patients with CTD-PAH were 37.0–47.1, 14.1–21.7 and 21.0–108.0 m, respectively. ERAs were less effective in patients with CTD-PAH than all-form patients with PAH: 14.1 m (−4.4–32.6 m) vs 39.5 m (19.5–59.6 m) for bosentan and 21.7 m (2.2–41.3 m) vs 44.2 m (30.2–58.2 m) for ambrisentan. Conclusions All three types of PAH agent are effective. However, ERAs may be a less effective choice against CTD-PAH; further studies are

  3. Association between a Functional HLA-G 14-bp Insertion/deletion Polymorphism and Susceptibility to Autoimmune Diseases: A Meta-analysis.

    PubMed

    Lee, Y H; Bae, S-C

    2015-12-09

    The aim of this study was to determine whether a functional human leukocyte antigen-G (HLA-G) 14-bp insertion (I)/deletion (D) polymorphism is associated with susceptibility to autoimmune diseases. A meta-analysis was conducted to assess the association between an HLA-G 14-bp I/D polymorphism and autoimmune diseases using 1) allele contrast, as well as 2) recessive, 3) dominant, and 4) codominant models. Sixteen articles that included 20 comparative studies with 3,555 patients and 5,225 controls were included in the meta-analysis. These studies were performed on nine Caucasian, six South American, three Asian, one Arab, and one African population samples. Our meta-analysis revealed no association between autoimmune diseases and the HLA-G 14-bp I/D polymorphism [odds ratio (OR) for allele I = 1.055; 95% confidence interval (CI) = 0.963-1.156; p = 0.251)]. However, meta-analysis according to autoimmune disease type revealed an association between systemic lupus erythematosus (SLE) and the II+ID genotype of the HLA-G 14-bp I/D polymorphism (OR = 1.205; 95% CI = 1.036-1.403; p = 0.016). Furthermore, analysis using a codominant model revealed an association between this polymorphism and SLE (OR for ID vs. DD = 1.203; 95% CI = 1.024-1.413; p = 0.024). In contrast, our meta-analysis revealed no association between rheumatoid arthritis (RA), multiple sclerosis (MS), or Crohn's disease (CD) and the HLA-G 14-bp I/D polymorphism. This meta-analysis showed that the HLA-G 14-bp I/D polymorphism is associated with susceptibility to a subgroup of autoimmune diseases such as SLE, but not RA, MS, or CD. These results support the existence of an association between the HLA-G gene and a subgroup of autoimmune diseases.

  4. Association of PDE4B Polymorphisms with Susceptibility to Schizophrenia: A Meta-Analysis of Case-Control Studies

    PubMed Central

    Feng, Yanguo; Cheng, Dejun; Zhang, Chaofeng; Li, Yuchun; Zhang, Zhiying; Wang, Juan; Shi, Yuzhong

    2016-01-01

    Background The PDE4B single nucleotide polymorphisms (SNPs) have been reported to be associated with schizophrenia risk. However, current findings are ambiguous or even conflicting. To better facilitate the understanding the genetic role played by PDE4B in susceptibility to schizophrenia, we collected currently available data and conducted this meta-analysis. Methods A comprehensive electronic literature searching of PubMed, Embase, Web of Science and Cochrane Library was performed. The association between PDE4B SNPs and schizophrenia was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs) under allelic, dominant and recessive genetic models. The random effects model was utilized when high between-study heterogeneity (I2 > 50%) existed, otherwise the fixed effects model was used. Results Five studies comprising 2376 schizophrenia patients and 3093 controls were finally included for meta-analysis. The rs1040716 was statistically significantly associated with schizophrenia risk in Asian and Caucasian populations under dominant model (OR = 0.87, 95% CI: 0.76–0.99, P = 0.04). The rs2180335 was significantly related with schizophrenia risk in Asian populations under allelic (OR = 0.82, 95% CI: 0.72–0.93, P = 0.003) and dominant (OR = 0.75, 95% CI: 0.64–0.88, P < 0.001) models. A significant association was also observed between rs4320761 and schizophrenia in Asian populations under allelic model (OR = 0.87, 95% CI: 0.75–1.00, P = 0.048). In addition, a strong association tendency was found between rs6588190 and schizophrenia in Asian populations under allelic model (OR = 0.87, 95% CI: 0.76–1.00, P = 0.055). Conclusion This meta-analysis suggests that PDE4B SNPs are genetically associated with susceptibility to schizophrenia. However, due to limited sample size, more large-scale, multi-racial association studies are needed to further clarify the genetic association between various PDE4B variants and schizophrenia. PMID:26756575

  5. A Meta-Analysis of the Association between ESR1 Genetic Variants and the Risk of Breast Cancer

    PubMed Central

    Yang, Jiaying; Ma, Xu; Dai, Qiaoyun; Huang, Hao; Wang, Lina; Liu, Pei

    2016-01-01

    Background Single nucleotide polymorphisms (SNPs) in the estrogen receptor gene (ESR1) play critical roles in breast cancer (BC) susceptibility. Genome-wide association studies have reported that SNPs in ESR1 are associated with BC susceptibility; however, the results of recent studies have been inconsistent. Therefore, we performed this meta-analysis to obtain more accurate and credible results. Methods We pooled published literature from PubMed, EMBASE, and Web of Science and calculated odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of associations using fixed effects models and random effects models. Twenty relevant case-control and cohort studies of the 3 related SNPs were identified. Results Three SNPs of the ESR1 gene, rs2077647:T>C, rs2228480:G>A and rs3798577:T>C, were not associated with increased BC risk in our overall meta-analysis. Stratified analysis by ethnicity showed that in Caucasians, the rs2228480 AA genotype was associated with a 26% decreased risk of BC compared with the GG genotype (OR = 0.740, 95% CI: 0.555–0.987). The C allele of the rs3798577:T>C variant was associated with decreased BC risk in Asians (OR = 0.828, 95% CI: 0.730–0.939), while Caucasians with this allele were found to experience significantly increased BC risk (OR = 1.551, 95% CI: 1.037–2.321). A non-significant association between rs2077647 and BC risk was identified in all of the evaluated ethnic populations. Conclusion Rs3798577 was associated with an increased risk of BC in Caucasian populations but a decreased risk in Asians. Rs2228480 had a large protective effect in Caucasians, while rs2077647 was not associated with BC risk. PMID:27070141

  6. Association between the methylenetetrahydrofolate reductase gene C677T polymorphism and sudden sensorineural hearing loss: a meta-analysis.

    PubMed

    Shu, Jingcheng; Yin, Shihua; Tan, An-Zhou; He, Meirong

    2015-09-01

    A variety of epidemiological studies have evaluated the association between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and sudden sensorineural hearing loss (SSNHL), but the results were inconsistent. The aim of this meta-analysis was to clarify more accurately the association of this polymorphism with SSNHL. A systematic literature search of the associated studies up to May 1, 2014, was conducted using the following electronic databases: PubMed, Embase, Medline, and the China National Knowledge Infrastructure. Statistical analyses were performed by STATA12.0 software, with odds ratios (ORs) and their 95 % confidence intervals (CIs). Six eligible studies including covering 1,271 objects were identified. A pooled analysis of these studies showed no significant association between C677T polymorphism and risk of SSNHL: T vs. C (OR = 1.334, POR = 0.105); TT vs. CC (OR = 1.580, POR = 0.231); CT vs. CC (OR = 1.500, POR = 0.123); TT vs. CC + CT (OR = 1.326, POR = 0.293); and TT + CT vs. CC (OR = 1.540, POR = 0.102). But in subgroup analysis, a significant association was found in European populations (T vs. C, OR = 1.542, 95 % CI 1.008-2.359, P = 0.046; TT vs. CT + CC, OR = 1.856, 95 % CI 1.245-2.767, P = 0.002). There was no significant association in any model in the Asian populations. The present meta-analysis suggests that MTHFR gene C677T polymorphism is significantly associated with increased risk of SSNHL disease in European populations, but no statistically significant association was found between the MTHFR C677T gene mutation and SSNHL in Asian. Further large and well-designed studies are needed to confirm this association.

  7. Meta-Analysis of the Association Between Whole and Refined Grain Consumption and Stroke Risk Based on Prospective Cohort Studies.

    PubMed

    Chen, Jianguo; Huang, Qingfeng; Shi, Wei; Yang, Liu; Chen, Jian; Lan, Qing

    2016-10-01

    The association between whole and refined grain consumption and stroke risk remains unclear. A search using MEDLINE and EMBASE databases was performed through February 29, 2016. Seven prospective studies with a total of 446 451 subjects and 5892 stroke events were included. The summary relative risk (SRR) of stroke for the high versus low consumption was 0.95 (95% confidence interval [CI] = 0.83-1.14) for total grains, 0.92 (95% CI = 0.72-1.17) for whole grains, and 0.99 (95% CI = 0.84-1.16) for refined grains. Diets rich in whole grains were inversely associated with ischemic stroke risk (SRR = 0.75, 95% CI = 0.60-0.95). Our meta-analysis revealed that whole and refined grain consumption is not associated with total stroke risk; however, whole grain consumption is associated with reduced ischemic stroke risk.

  8. The associations between five polymorphisms of vascular endothelial growth factor and renal cell carcinoma risk: an updated meta-analysis

    PubMed Central

    Wang, Jiao; Shen, ChangXin; Fu, YouRong; Yu, Tian; Song, JingJing

    2017-01-01

    Background Vascular endothelial growth factor (VEGF) is a key mediator that plays an important role in angiogenesis, tumor growth, and tumor metastasis. The associations between five polymorphisms of VEGF (rs3025039, rs699947, rs10434, rs1570360, and rs2010963) and renal cell carcinoma (RCC) risk have been extensively investigated, but the currently available results are inconsistent and inconclusive. To obtain a more accurate assessment of the associations, we conducted a meta-analysis in this study. Materials and methods Relevant studies were collected systemically from the following three electronic databases: MEDLINE, Web of Science, and CNKI (Chinese National Knowledge Infrastructure). Statistical analyses were performed using Review Manager 5.2 in a fixed- or random-effects model. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to establish the strength of associations. Results A total of eight case–control studies with 1,936 RCC cases and 2,770 controls fulfilling the inclusion criteria were selected for this meta-analysis. The pooled OR indicated that rs699947 polymorphism was significantly associated with RCC risk in all genetic models. A significant association was also found between the rs3025039 polymorphism and RCC risk in a homozygous model (TT vs CC: OR =1.38, 95% CI =1.11–1.72, P=0.004), a dominant model (CT+TT vs CC: OR =1.21, 95% CI =1.05–1.39, P=0.01), and a recessive model (TT vs CC+CT: OR =1.28, 95% CI =1.04–1.57, P=0.02). After a subgroup analysis of ethnicity in the allele contrast model of rs3025039 polymorphism, we found a significant relationship in the allele contrast model (T vs C: OR =1.21, 95% CI =1.05–1.40, P=0.007) in the Asian population. With regard to rs10434 polymorphism, significant association was observed only in a homozygous model (GG vs AA: OR =0.75, 95% CI =0.57–0.98, P=0.03). As to rs1570360 or rs2010963, we did not observe any relationship between the two polymorphisms and RCC

  9. The association between driving anger and driving outcomes: A meta-analysis of evidence from the past twenty years.

    PubMed

    Zhang, Tingru; Chan, Alan H S

    2016-05-01

    Through the use of meta-analysis, this study investigated the relationships between driving anger and five types of driving outcomes (aggressive driving, risky driving, driving errors, near misses and accidents). The moderating effects of three variables (age, study publication year, and participants' country of origin) on these relationships were also examined. A total of 51 studies published over the past two decades met the inclusion criteria for the meta-analysis. The results showed that driving anger significantly predicted all three types of aberrant driving, with zero-order correlations of 0.312, 0.243, and 0.179 with aggressive driving, risky driving and driving errors, respectively. The correlations between driving anger and accident-related conditions, though at relatively weaker levels, were still statistically significant. Tests for effects of the moderating variables suggested that driving anger was a stronger predictor of risky driving among young drivers than among old drivers. Also, the anger-aggression association was found to decrease over time and vary across countries. The implications of the results and the directions for future research are discussed.

  10. The association between dietary vitamin A intake and pancreatic cancer risk: a meta-analysis of 11 studies

    PubMed Central

    Zhang, Tao; Chen, Hongqiang; Qin, Shiyong; Wang, Minghai; Wang, Xianming; Zhang, Xin; Liu, Fei; Zhang, Shuguang

    2016-01-01

    Whether dietary vitamin A intake could reduce pancreatic cancer risk is still conflicting. We therefore conducted a meta-analysis to summarize the evidence from epidemiological studies. We searched the databases of PubMed and Web of Knowledge up to July 2016. Random model was used to combine study-specific relative risks (RR) and 95% confidence interval (CI). Publication bias was assessed by Egger regression asymmetry test and Begg's funnel plot. Eleven studies (10 case-control studies and 1 cohort study) involving 2705 pancreatic cancer cases were included in the present study. The RR (95% CI) of pancreatic cancer for highest category of vitamin A intake compared with lowest category was 0.839 (95% CI=0.712–0.988) with low heterogeneity detected (I2=17.8%, Pheterogeneity=0.274). The relationships were also significant for studies designed by case-control [RR=0.808, 95% CI=0.690–0.947], as well as in European population [RR=0.821, 95% CI=0.693–0.972]. No evidence of publication bias was found. This meta-analysis demonstrated that dietary vitamin A intake might inversely associated with the risk of pancreatic cancer. PMID:27756825

  11. Association between cooking oil fume exposure and lung cancer among Chinese nonsmoking women: a meta-analysis.

    PubMed

    Xue, Yingbo; Jiang, Ying; Jin, Shan; Li, Yong

    2016-01-01

    Lung cancer has been the main cause of cancer death around the world. Cigarette smoking has been identified as a risk factor for lung cancer in males. However, the etiological factors in nonsmoking women remain elusive. A meta-analysis was conducted to evaluate the relationship between cooking oil fume exposure and lung cancer among Chinese nonsmoking women. Thirteen articles containing three population-based case-control and ten hospital-based case-control studies were included in this meta-analysis. These studies with a total of 3,596 lung cancer women and 6,082 healthy controls were analyzed by RevMan 5.3. Fixed effects model or random effects model was used to obtain pooled estimates of risk ratio. The risk ratios with a 95% CI were 1.74 (95% CI =1.57-1.94) and 2.11 (95% CI =1.54-2.89), respectively. Cooking oil fume exposure as well as not using a kitchen ventilator when cooking was significantly associated with lung cancer among nonsmoking women (Z=10.07, P<0.00001; Z=4.65, P<0.00001). Cooking oil fume exposure, especially lacking a fume extractor, may increase the risk of lung cancer among Chinese nonsmoking women.

  12. Is meditation associated with altered brain structure? A systematic review and meta-analysis of morphometric neuroimaging in meditation practitioners.

    PubMed

    Fox, Kieran C R; Nijeboer, Savannah; Dixon, Matthew L; Floman, James L; Ellamil, Melissa; Rumak, Samuel P; Sedlmeier, Peter; Christoff, Kalina

    2014-06-01

    Numerous studies have begun to address how the brain's gray and white matter may be shaped by meditation. This research is yet to be integrated, however, and two fundamental questions remain: Is meditation associated with altered brain structure? If so, what is the magnitude of these differences? To address these questions, we reviewed and meta-analyzed 123 brain morphology differences from 21 neuroimaging studies examining ∼300 meditation practitioners. Anatomical likelihood estimation (ALE) meta-analysis found eight brain regions consistently altered in meditators, including areas key to meta-awareness (frontopolar cortex/BA 10), exteroceptive and interoceptive body awareness (sensory cortices and insula), memory consolidation and reconsolidation (hippocampus), self and emotion regulation (anterior and mid cingulate; orbitofrontal cortex), and intra- and interhemispheric communication (superior longitudinal fasciculus; corpus callosum). Effect size meta-analysis (calculating 132 effect sizes from 16 studies) suggests a global 'medium' effect size (Cohen's d¯=0.46; r¯=.19). Publication bias and methodological limitations are strong concerns, however. Further research using rigorous methods is required to definitively link meditation practice to altered brain morphology.

  13. Association of Matrix Metalloproteinase 9 C-1562T Polymorphism with Genetic Susceptibility to Myocardial Infarction: A Meta-Analysis

    PubMed Central

    Juan, Zhang; Wei-Guo, Zhang; Heng-Liang, Song; Da-Guo, Wan

    2015-01-01

    Background Myocardial infarction (MI) is the major cause of death by disease in the world. Many studies have identified the associations between matrix metalloproteinase 9 (MMP9) C-1562T polymorphisms and MI. However, the results remain inconclusive. To clarify the role of MMP9 C-1562T polymorphism in MI risk, we conducted a systematic review and large-scale meta-analysis. Methods Studies published between January 2005 and March 2014 were obtained from the electronic databases PubMed, Medline, and Embase. The odds ratios (ORs) with 95% CIs were calculated for comparisons of the alleles and genotypes in the overall population and in ethnicity subgroups to measure the strength of genetic associations. Results A total of 7 related studies, including 3952 MI cases and 4977 healthy control subjects were included in our meta-analysis. Our results show a statistically significant association between T allele and MI in the overall population (OR = 1.23; 95% CI, 1.02–1.48; P = 0.03). The risk of MI was also significantly higher in patients carrying the T allele (TC + TT genotypes) than in those with the CC genotype (P < 0.05). In stratified analysis by ethnicity, we found the T allele was strongly associated with MI in white populations, whereas in Asian populations there appeared no significant association. Conclusions Our data show that the MMP9 C-1562T polymorphism is a risk factor associated with increased MI susceptibility in the total population and white populations, although no significant association was observed in Asians populations. Further studies with larger sample sizes and assessing gene–gene and gene–environment interactions are required. PMID:26082814

  14. Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

    PubMed Central

    Springelkamp, Henriët.; Höhn, René; Mishra, Aniket; Hysi, Pirro G.; Khor, Chiea-Chuen; Loomis, Stephanie J.; Bailey, Jessica N. Cooke; Gibson, Jane; Thorleifsson, Gudmar; Janssen, Sarah F.; Luo, Xiaoyan; Ramdas, Wishal D.; Vithana, Eranga; Nongpiur, Monisha E.; Montgomery, Grant W.; Xu, Liang; Mountain, Jenny E.; Gharahkhani, Puya; Lu, Yi; Amin, Najaf; Karssen, Lennart C.; Sim, Kar-Seng; van Leeuwen, Elisabeth M.; Iglesias, Adriana I.; Verhoeven, Virginie J. M.; Hauser, Michael A.; Loon, Seng-Chee; Despriet, Dominiek D. G.; Nag, Abhishek; Venturini, Cristina; Sanfilippo, Paul G.; Schillert, Arne; Kang, Jae H.; Landers, John; Jonasson, Fridbert; Cree, Angela J.; van Koolwijk, Leonieke M. E.; Rivadeneira, Fernando; Souzeau, Emmanuelle; Jonsson, Vesteinn; Menon, Geeta; Mitchell, Paul; Wang, Jie Jin; Rochtchina, Elena; Attia, John; Scott, Rodney; Holliday, Elizabeth G.; Wong, Tien-Yin; Baird, Paul N.; Xie, Jing; Inouye, Michael; Viswanathan, Ananth; Sim, Xueling; Weinreb, Robert N.; de Jong, Paulus T. V. M.; Oostra, Ben A.; Uitterlinden, André G.; Hofman, Albert; Ennis, Sarah; Thorsteinsdottir, Unnur; Burdon, Kathryn P.; Allingham, R. Rand; Brilliant, Murray H.; Budenz, Donald L.; Cooke Bailey, Jessica N.; Christen, William G.; Fingert, John; Friedman, David S.; Gaasterland, Douglas; Gaasterland, Terry; Haines, Jonathan L.; Hauser, Michael A.; Kang, Jae Hee; Kraft, Peter; Lee, Richard K.; Lichter, Paul R.; Liu, Yutao; Loomis, Stephanie J.; Moroi, Sayoko E.; Pasquale, Louis R.; Pericak-Vance, Margaret A.; Realini, Anthony; Richards, Julia E.; Schuman, Joel S.; Scott, William K.; Singh, Kuldev; Sit, Arthur J.; Vollrath, Douglas; Weinreb, Robert N.; Wiggs, Janey L.; Wollstein, Gadi; Zack, Donald J.; Zhang, Kang; Donnelly (Chair), Peter; Barroso (Deputy Chair), 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 (Chair), Christopher G.; Blackwell, Jenefer M.; Brown, Matthew A.; Corvin, Aiden; Spencer, Chris C. A.; Spector, Timothy D.; Mirshahi, Alireza; Saw, Seang-Mei; Vingerling, Johannes R.; Teo, Yik-Ying; Haines, Jonathan L.; Wolfs, Roger C. W.; Lemij, Hans G.; Tai, E-Shyong; Jansonius, Nomdo M.; Jonas, Jost B.; Cheng, Ching-Yu; Aung, Tin; Viswanathan, Ananth C.; Klaver, Caroline C. W.; Craig, Jamie E.; Macgregor, Stuart; Mackey, David A.; Lotery, Andrew J.; Stefansson, Kari; Bergen, Arthur A. B.; Young, Terri L.; Wiggs, Janey L.; Pfeiffer, Norbert; Wong, Tien-Yin; Pasquale, Louis R.; Hewitt, Alex W.; van Duijn, Cornelia M.; Hammond, Christopher J.

    2014-01-01

    Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition. PMID:25241763

  15. Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy

    PubMed Central

    Williams, Winfred W.; Salem, Rany M.; McKnight, Amy Jayne; Sandholm, Niina; Forsblom, Carol; Taylor, Andrew; Guiducci, Candace; McAteer, Jarred B.; McKay, Gareth J.; Isakova, Tamara; Brennan, Eoin P.; Sadlier, Denise M.; Palmer, Cameron; Söderlund, Jenny; Fagerholm, Emma; Harjutsalo, Valma; Lithovius, Raija; Gordin, Daniel; Hietala, Kustaa; Kytö, Janne; Parkkonen, Maija; Rosengård-Bärlund, Milla; Thorn, Lena; Syreeni, Anna; Tolonen, Nina; Saraheimo, Markku; Wadén, Johan; Pitkäniemi, Janne; Sarti, Cinzia; Tuomilehto, Jaakko; Tryggvason, Karl; Österholm, Anne-May; He, Bing; Bain, Steve; Martin, Finian; Godson, Catherine; Hirschhorn, Joel N.; Maxwell, Alexander P.; Groop, Per-Henrik; Florez, Jose C.

    2012-01-01

    We formed the GEnetics of Nephropathy–an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 × 10−9). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated. PMID:22721967

  16. Meta-analysis on the association of VEGFR1 genetic variants with sunitinib outcome in metastatic renal cell carcinoma patients

    PubMed Central

    Liu, Xiaoyan; Swen, Jesse J.; Boven, Epie; Castellano, Daniel; Gelderblom, Hans; Mathijssen, Ron H.J.; Rodríguez-Antona, Cristina; García-Donas, Jesus; Rini, Brian I.; Guchelaar, Henk-Jan

    2017-01-01

    VEGFR1 rs9582036 and rs9554320 were previously reported the association with sunitinib progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). Hereafter, the association of both single nucleotide polymorphisms (SNPs) with PFS/OS was confirmed in two independent mRCC cohorts. The aim of the current study was to validate the associations of both SNPs with sunitinib outcome in three independent well-characterized cohorts (SUTOX, CCF and SOGUG) including 286 sunitinib-treated mRCC patients, as well as to perform a meta-analysis of current and published data combined. We found that rs9582036 and rs9554320 showed a significant association with sunitinib PFS in the CCF cohort (HR: 0.254, 95%CI: 0.092-0.703; P=0.008 and HR: 0.430, 95%CI: 0.200-0.927; P=0.031, respectively). Patients with the variant genotype of rs9582036 and rs9554320 had a shorter median PFS. No significant association of both SNPs with sunitinib PFS or OS was detected in either the SUTOX or SOGUG cohort. After the combination of all available data into a meta-analysis, the association of both SNPs with sunitinib PFS or OS did not achieve the threshold for statistical significance. Our findings suggest that, although VEGFR1 rs9582036 and rs9554320 are involved in sunitinib therapy outcome, its clinical use as biomarkers for prediction of sunitinib outcome in mRCC patients is limited, due to inconsistent findings when analyzing all existing studies together. PMID:27901483

  17. Is coffee consumption associated with a lower risk of hyperuricaemia or gout? A systematic review and meta-analysis

    PubMed Central

    Zhang, Yi; Yang, Tuo; Zeng, Chao; Wei, Jie; Li, Hui; Xiong, Yi-lin; Yang, Ye; Ding, Xiang; Lei, Guanghua

    2016-01-01

    Objectives To examine the associations of coffee consumption with the serum uric acid (SUA) level, hyperuricaemia (HU) and gout. Design Systematic review and meta-analysis. Data sources and study eligibility criteria A comprehensive literature search up to April 2015, using PubMed and EMBASE databases, was conducted to identify the observational researches that examined the associations of coffee consumption with the SUA level, HU and gout. The standard mean difference (SMD), OR, relative risk (RR) and their corresponding 95% CIs for the highest and the lowest categories of coffee intake were determined. Results A total of 11 observational studies (6 cross-sectional, 3 cohort and 2 case–control studies) were included in this systematic review and meta-analysis. The combined SMD suggested that there was no significant difference between the highest and the lowest coffee intake categories in terms of the SUA level (SMD=−0.09, 95% CI −0.23 to 0.05; p=0.21). Meanwhile, the overall multivariable adjusted OR for HU showed no significant difference between the highest and the lowest coffee intake categories (OR=0.84, 95% CI 0.65 to 1.09; p=0.20). However, the overall multivariable adjusted RR for gout showed a significant inverse association between coffee consumption and the incidence of gout (RR=0.43, 95% CI 0.31 to 0.59, p<0.001). Conclusions Current evidences are insufficient to validate the association between coffee consumption and a lower risk of HU. Owing to the limited number of studies, the available data show that coffee consumption may be associated with a lower risk of incident gout. Further well-designed prospective researches and randomised controlled trials are therefore needed to elaborate on these issues. PMID:27401353

  18. Meta-Analysis on Associations of RGS1 and IL12A Polymorphisms with Celiac Disease Risk

    PubMed Central

    Guo, Cong-Cong; Wang, Man; Cao, Feng-Di; Huang, Wei-Huang; Xiao, Di; Ye, Xing-Guang; Ou, Mei-Ling; Zhang, Na; Zhang, Bao-Huan; Liu, Yang; Yang, Guang; Jing, Chun-Xia

    2016-01-01

    The pathogenesis of celiac disease (CD) has been related to polymorphisms in the regulator of G-protein signaling 1 (RGS1) and interleukin-12 A (IL12A) genes, but the existing findings are inconsistent. Our aim is to investigate the associations of two single-nucleotide polymorphisms (SNPs) (rs2816316 in RGS1 and rs17810546 in IL12A) with CD risk using meta-analysis. We searched PubMed and Web of Science on RGS1 rs2816316 and IL12A rs17810546 with CD risk. Odds ratio (OR) and 95% confidence interval (CI) of each SNP were estimated. All statistical analyses were performed on Stata 12.0. A total of seven studies were retrieved and analyzed. The available data indicated the minor allele C of rs2816316 was negatively associated with CD (C vs. A: OR = 0.77, 95% CI = 0.74–0.80), and a positive association was found for the minor allele G of rs17810546 (G vs. A: OR = 1.37, 95% CI = 1.31–1.43). The co-dominant model of genotype effect confirmed the significant associations between RGS1 rs2816316/IL12A rs17810546 and CD. No evidence of publication bias was observed. Our meta-analysis supports the associations of RGS1 and IL12A with CD and strongly calls for further studies to better understand the roles of RGS1 and IL12A in the pathogenesis of CD. PMID:27043536

  19. Serum uric acid level and association with cognitive impairment and dementia: systematic review and meta-analysis.

    PubMed

    Khan, Aamir A; Quinn, Terence J; Hewitt, Jonathan; Fan, Yuhua; Dawson, Jesse

    2016-02-01

    Serum uric acid (sUA) level may be associated with cognitive impairment/dementia. It is possible this relationship varies with dementia subtype, particularly between vascular dementias (VaD) and Alzheimer's (AD) or Parkinson's disease (PDD)-related dementia. We aimed to present a synthesis of all published data on sUA and relationship with dementia/cognition through systematic review and meta-analysis. We included studies that assessed the association between sUA and any measure of cognitive function or a clinical diagnosis of dementia. We pre-defined subgroup analyses for patients with AD, VaD, PDD, mild cognitive impairment (MCI), and mixed or undifferentiated. We assessed risk of bias/generalizability, and where data allowed, we performed meta-analysis to describe pooled measures of association across studies. From 4811 titles, 46 papers (n = 16,688 participants) met our selection criteria. Compared to controls, sUA was lower in dementia (SDM -0.33 (95%CI)). There were differences in association by dementia type with apparent association for AD (SDM -0.33 (95%CI)) and PDD (SDM -0.67 (95%CI)) but not in cases of mixed dementia (SDM 0.19 (95%CI)) or VaD (SDM -0.05 (95%CI)). There was no correlation between scores on Mini-Mental State Examination and sUA level (summary r 0.08, p = 0.27), except in patients with PDD (r 0.16, p = 0.003). Our conclusions are limited by clinical heterogeneity and risk of bias in studies. Accepting this caveat, the relationship between sUA and dementia/cognitive impairment is not consistent across all dementia groups and in particular may differ in patients with VaD compared to other dementia subtypes.

  20. The Nature and Severity of Cognitive Impairment Associated with Adjuvant Chemotherapy in Women with Breast Cancer: A Meta-Analysis of the Current Literature

    ERIC Educational Resources Information Center

    Falleti, Marina G.; Sanfilippo, Antonietta; Maruff, Paul; Weih, LeAnn; Phillips, Kelly-Anne

    2005-01-01

    Objective: Several studies have identified that adjuvant chemotherapy for breast cancer is associated with cognitive impairment; however, the magnitude of this impairment is unclear. This study assessed the severity and nature of cognitive impairment associated with adjuvant chemotherapy by conducting a meta-analysis of the published literature to…

  1. A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

    PubMed Central

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

    2015-01-01

    Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size. PMID:26343387

  2. Genetic Variant in MTRR, but Not MTR, Is Associated with Risk of Congenital Heart Disease: An Integrated Meta-Analysis

    PubMed Central

    Zhong, Rong; Zou, Li; Zhu, Beibei; Chen, Wei; Shen, Na; Ke, Juntao; Lou, Jiao; Wang, Zhenling; Sun, Yu; Liu, Lifeng; Song, Ranran

    2014-01-01

    Background Congenital heart disease (CHD) is one of the most common birth defects and the leading cause of deaths among individuals with congenital structural abnormalities worldwide. Both Methionine synthase reductase (MTRR) and Methionine synthase (MTR) are key enzymes involved in the metabolic pathway of homocysteine, which are significant in the earlier period embryogenesis, particularly in the cardiac development. Evidence is mounting for the association between MTRR A66G (rs1801394)/MTR A2756G (rs1805087) and the CHD risk, but results are controversial. Therefore, we conducted a meta-analysis integrating case-control and transmitted disequilibrium test (TDT) studies to obtain more precise estimate of the associations of these two variants with the CHD risk. Methods To combine case-control and TDT studies, we used the Catmap package of R software to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results A total of 9 reports were included in the final meta-analysis. Eight of them comprised of 914 cases, 964 controls, and 441 families that were germane to MTRR A66G polymorphism; and 4 reports comprised of 250 cases, 205 controls, and 53 families that were relevant to MTR A2756G polymorphism. The pooled OR for the MTRR 66 G allele versus A allele was 1.35 (95% CI = 1.14–1.59, P<0.001, Pheterogeneity = 0.073). For MTR A2756G, the G allele conferred a pooled OR of 1.10 (95% CI = 0.78–1.57, P = 0.597, Pheterogeneity = 0.173) compared with the A allele. Sensitivity analyses were carried out to asses the effects of each individual study on the pooled OR, indicating the stability of the outcome. Moreover, positive results were also obtained in all subgroups stratified by study type and ethnicity except the subgroup of TDT studies in MTRR A66G variant. Conclusions This meta-analysis demonstrated a suggestive result that the A66G variant in MTRR, but not the A2756G in MTR, may be associated with the increase of CHD risks. PMID

  3. Meta-Analysis on the Association of ALDH2 Polymorphisms and Type 2 Diabetic Mellitus, Diabetic Retinopathy

    PubMed Central

    Li, Guang-Yi; Li, Zi-Bo; Li, Fang; Dong, Li-Ping; Tang, Liang; Xiang, Ju; Li, Jian-Ming; Bao, Mei-Hua

    2017-01-01

    Type 2 diabetic mellitus (T2DM) is a disease with high prevalence and a major cause for death worldwide. Diabetic retinopathy (DR) is one of the major manifestation of diabetes. Aldehyde dehydrogenease 2 (ALDH2) detoxifies aldehyde produced during ethanol metabolism and oxidative stress. It has been found that the polymorphism in ALDH2 rs671 is probably associated with the risk of T2DM and DR. However, a lot of inconsistency and controversy still exists. In order to get a more precise and comprehensive estimation for the association between ALDH2 polymorphism with the risk of T2DM and DR, we conducted the present meta-analysis. A comprehensive literature search was conducted using databases, such as Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Database, for all related studies. The included studies met the inclusion criteria, such as being case-control studies about the association of ALDH2 polymorphism and T2DM or DR susceptibility, with sufficient data for the present analysis. Eight studies with 2374 cases and 6694 controls were involved in the present meta-analysis. The results indicated a significant lower risk of T2DM for *1/*1 genotype in homozygous models (*1/*1 vs. *2/*2, OR = 0.31, 95% CI = 0.11–0.89, p = 0.03) and in the dominant model (*1/*1 vs. *2/*2 + *1/*2, OR = 0.61, 95% CI = 0.37–1.00, p = 0.05). Subgroup analysis by ethnicity found a significant lower risk of T2DM in Chinese in all genotype models. No significant relation was found between ALDH2 rs671 and DR. In conclusion, the current meta-analysis indicated that ALDH2 rs671 was significantly related with T2DM. The ALDH2 rs671 might be able to be used as a predictor for the risk of T2DM. However, due to the existence of heterogeneity and publication bias in the involved studies, our results should be interpreted with caution. PMID:28208752

  4. Association between the COMT 158 G/A polymorphism and lung cancer risk: a meta-analysis.

    PubMed

    Peng, Shifeng; Tong, Xiang; Liu, Sitong; Feng, Yulin; Fan, Hong

    2015-01-01

    Catechol-O-methyltransferase (COMT) 158 G/A gene polymorphism seem to associate with lung cancer, but the results are inconclusive. This meta-analysis aims to investigate the association between COMT 158 G/A gene polymorphism and lung cancer susceptibility. We searched PubMed, Embase, China National Knowledge Infrastructure (CNKI), VIP Chinese science and technology periodical database (VIP) and Wanfang databases up to March 25, 2015 for articles on the connection between the COMT 158 G/A polymorphism and the risk of lung cancer. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were used to estimate the connection. STATA (Version 12.0) was adopted for data analysis. Overall, 6 articles of 7 studies including 2,293 cases and 2,768 controls were included in our meta-analysis. In general analysis, no significant association was found between COMT 158 G/A polymorphism and the risk of lung cancer (AA + AG vs. GG: OR 1.14, 95% CI 0.90-1.44, P=0.28). However, in subgroup analysis of different method of genotyping, we found significant increase of lung cancer risk (OR 1.30, 95% CI 1.04-1.62, I(2)=61.5%, P=0.02), also there was significant association between COMT 158 G/A polymorphism and the risk of lung cancer in Chinese non-smoker women of unsorted cancer type (OR 1.48, 95% CI 1.24-1.77, I(2)=0%, P=0.00). The study indicates that COMT 158 G/A G->A gene transition might contribute to lung cancer, especially in Chinese non-smoker women.

  5. Association between CTLA-4 exon-1 +49A/G polymorphism and asthma: an updated meta-analysis

    PubMed Central

    Yao, Ying-Shui; Wang, Lin-Hong; Chang, Wei-Wei; He, Lian-Ping; Li, Jie; Jin, Yue-Long; Li, Chao-Pin

    2015-01-01

    The results of studies on association between CTLA-4 exon-1 +49A/G (rs231775) polymorphism and susceptibility to asthma are controversial. To derive a more precise estimation of the relationship between the CTLA-4 exon-1 +49A/G polymorphism and asthma, a meta-analysis of 15 published case-control studies was performed. 15 studies meeting our inclusion criteria comprising 4006 asthma cases and 3729 controls were included. The effect summary odds ratio (OR) and 95% confidence intervals were obtained. Publication bias was tested by funnel plot, Egger’s test and heterogeneity was assessed. The combined results showed that there were significant differences in genotype distribution between asthma cases and control on the basis of all studies, GG + GA versus AA (OR = 0.76, 95% CI: 0.62-0.93; P = 0.008). When stratifying for the race, the phenomenon was found that asthma cases had a significantly higher frequency of GG/GA versus AA (OR = 0.71; 95% CI: 0.51-0.99; P = 0.04) than control in Caucasian. Stratifying subjects by age indicated an association between CTLA-4 +49 GG + GA genotype and asthma in children (OR = 0.75; 95% CI: 0.62-0.90; P = 0.002), but no association in adults (OR = 0.93; 95% CI: 0.76-1.14; P = 0.48). Furthermore, significant association was observed in atopic asthma under the fixed-effects model (GG + GA vs. AA: P = 0.03, OR = 0.81, 95% CI = 0.67-0.98, P heterogeneity = 0.22). Our meta-analysis results suggest that CTLA-4 exon-1 +49A/G polymorphism might be a risk factor for asthma susceptibility, at least in Caucasian, children, and patients with atopy status. PMID:26064199

  6. Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies.

    PubMed

    Martinón-Torres, Federico; Png, Eileen; Khor, Chiea Chuen; Davila, Sonia; Wright, Victoria J; Sim, Kar Seng; Vega, Ana; Fachal, Laura; Inwald, David; Nadel, Simon; Carrol, Enitan D; Martinón-Torres, Nazareth; Alonso, Sonia Marcos; Carracedo, Angel; Morteruel, Elvira; López-Bayón, Julio; Torre, Andrés Concha; Monge, Cristina Calvo; de Aguilar, Pilar Azcón González; Torné, Elisabeth Esteban; Martínez-Padilla, María Del Carmen; Martinón-Sánchez, José María; Levin, Michael; Hibberd, Martin L; Salas, Antonio

    2016-11-02

    Meningococcal disease (MD) remains an important infectious cause of life threatening infection in both industrialized and resource poor countries. Genetic factors influence both occurrence and severity of presentation, but the genes responsible are largely unknown. We performed a genome-wide association study (GWAS) examining 5,440,063 SNPs in 422 Spanish MD patients and 910 controls. We then performed a meta-analysis of the Spanish GWAS with GWAS data from the United Kingdom (combined cohorts: 897 cases and 5,613 controls; 4,898,259 SNPs). The meta-analysis identified strong evidence of association (P-value ≤ 5 × 10(-8)) in 20 variants located at the CFH gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR) = 0.62, 95% confidence interval (C.I.) = 0.52-0.73; P-value = 9.62 × 10(-9)). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR = 0.64, 95% C.I.) = 0.55-0.76, P-value = 3.25 × 10(-8)). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of CFH with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease.

  7. Gender differences in the association between childhood sexual abuse and risky sexual behaviours: A systematic review and meta-analysis.

    PubMed

    Abajobir, Amanuel Alemu; Kisely, Steve; Maravilla, Joemer Calderon; Williams, Gail; Najman, Jake Moses

    2017-01-01

    This meta-analytic review examines the association between childhood sexual abuse and risky sexual behaviours with sub-group analyses by gender. Systematic searches of electronic databases including MEDLINE, PubMed, EMBASE, and PsycINFO were performed using key terms. We used a priori criteria to include high quality studies and control for heterogeneities across eligible studies. The review was registered with PROSPERO and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The final meta-analysis applied fixed-effects model to generate pooled odds ratio (OR). Subgroup analyses were conducted to identify potential methodological moderators. The meta-analysis included 8 eligible studies (N=38,989, females=53.1%). The overall syndemic of risky sexual behaviors at adulthood was 1.59 times more common in childhood sexual abuse victims. There was a similar association between childhood sexual abuse in general and subsequent risky sexual behaviors in both females and males. However, in cases of substantiated childhood sexual abuse, there was a greater odds of risky sexual behaviors in females (OR=2.72) than males (OR=1.69). The magnitude of association of childhood sexual abuse and risky sexual behaviors was similar for males and females regardless of study time, study quality score and method of childhood sexual abuse measurement. There were nonsignificant overall and subgroup differences between males and females. Childhood sexual abuse is a significant risk factor for a syndemic of risky sexual behaviors and the magnitude is similar both in females and males. More research is needed to explore possible mechanisms of association.

  8. Association of Transforming Growth Factor Beta-1-509C/T Gene Polymorphism with Ischemic Stroke: A Meta Analysis

    PubMed Central

    Kumar, Pradeep; Kumar, Amit; Srivastava, Mukesh Kumar; Misra, Shubham; Pandit, Awadh Kishor; Prasad, Kameshwar

    2016-01-01

    Introduction: Transforming Growth Factor-Beta 1 (TGF-β1) is a pleiotropic cytokine with potent anti-inflammatory property, which has been considered as an essential risk factor in the inflammatory process of Ischemic Stroke (IS), by involving in the pathophysiological progression of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-β1 gene polymorphism has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide a relatively comprehensive account of the relation between -509C/T gene polymorphisms of TGF-β1 and susceptibility to IS. Methods: A review of literature for eligible genetic association Studies published before October 20, 2014 was conducted in the PubMed, EMBASE, Google Scholar and Trip database. The strength of association was calculated by pooled odds ratios (ORs) with 95% confidence intervals using RevMan 5.3 software. Heterogeneity was examined using Higgins I-squared, Tau-squared, and Chi-squared tests. Results: A total of 2 studies involving 614 cases and 617 controls were found. The overall estimates did not show any significant relation between TGF-β1-509C/T polymorphism and risk of IS under dominant (CC+CT vs. TT: OR=1.01, 95%CI=0.31 to 3.26; P=0.99), recessive (CC vs. CT+TT: OR=0.94, 95%CI=0.47 to 1.90; P=0.87), and allelic models (T vs. C: OR=1.06, 95%CI=0.55 to 2.04; P=0.86). Conclusion: This meta-analysis showed that TGF-β1-509C/T gene polymorphism has no significant association with the susceptibility of IS. Further well-designed prospective studies with larger sample size are needed to confirm these findings. PMID:27303603

  9. Association of OGG1 and MTHFR polymorphisms with age-related cataract: A systematic review and meta-analysis

    PubMed Central

    Liu, Yizhi

    2017-01-01

    Purpose To discern and confirm genetic biomarkers that help identify populations at high risk for age-related cataract (ARC). Methods A literature search was performed in the PubMed, Web of Science and China National Knowledge Internet databases for genetic association studies published before June 26, 2016 regarding ARC susceptibility. All genetic polymorphisms reported were systematically reviewed, followed by extraction of candidate genes/loci with sufficient genotype data in ≥3 studies for the meta-analysis. A random/fixed-effects model was used to calculate the pooled odds ratios and 95% confidence intervals to evaluate the associations considering multiple genetic models. Sensitivity analysis was also performed. Results A total of 144 polymorphisms in 36 genes were reported in the 61 previous genetic association studies. Thereby, three polymorphisms of two genes (8-oxoguanine DNA glycosylase-1 [OGG1]; methylenetetrahydrofolate reductase NADPH [MTHFR]) in eight studies were included in the meta-analysis. Regarding the OGG1-rs1052133, the GG (OR = 1.925; 95%CI, 1.181–3.136; p = 0.009) and CG (OR = 1.384; 95%CI, 1.171–1.636; p<0.001) genotypes indicated higher risk of ARC. For the MTHFR gene, the CC+TT genotype of rs1801133 might be protective (OR, 0.838; 95%CI, 0.710–0.989; p = 0.036), whereas the AA+CC genotype of rs1801131 indicated increased risk for the mixed subtype (OR = 1.517; 95%CI, 1.113–2.067; p = 0.008). Conclusions Polymorphisms of OGG1 and MTHFR genes are associated with ARC susceptibility and may help identify populations at high risk for ARC. PMID:28253266

  10. Increased All-Cause Mortality Associated With Digoxin Therapy in Patients With Atrial Fibrillation: An Updated Meta-Analysis.

    PubMed

    Chen, Ying; Cai, Xiaoyan; Huang, Weijun; Wu, Yanxian; Huang, Yuli; Hu, Yunzhao

    2015-12-01

    Digoxin is still commonly used in atrial fibrillation (AF) patients with and without heart failure (HF) for heart rate control. Studies concerning the detrimental effects of digoxin therapy in AF patients are inconsistent. This updated meta-analysis examined the association of digoxin therapy with all-cause mortality in AF patients, stratified by heart function status. We included observational studies with multivariate-adjusted data on digoxin and all-cause mortality in the analysis. The relative risks (RRs) of all-cause mortality were calculated and reported with 95% confidence intervals (95% CIs). Seventeen studies comprising 408,660 patients were included. Overall, in AF patients, digoxin treatment was associated with a significant increase in all-cause mortality after multivariate-adjustment (RR = 1.22; 95% CI 1.15-1.30). When stratified by heart function status, digoxin treatment was associated with a 14% increase in all-cause mortality in AF patients with HF (RR = 1.14, 95% CI 1.04-1.24), and a 36% increase in those without HF (RR = 1.36, 95% CI 1.18-1.56). The increased risk of all-cause mortality was significantly higher in AF patients without HF compared with those with HF (P for interaction = 0.04). This meta-analysis demonstrates that digoxin therapy was associated with a significant increase in all-cause mortality in AF patients, especially in those without HF. Given other available options, digoxin should be avoided as a first-line agent for heart rate control in AF patients.

  11. Association of CYP1B1 L432V polymorphism with urinary cancer susceptibility: a meta-analysis

    PubMed Central

    2014-01-01

    Abstract Background The Cytochrome P450 1B1 (CYP1B1) is a key P450 enzyme involved in the metabolism of exogenous and endogenous substrates. Previous studies have reported the existence of CYP1B1 L432V missense polymorphism in prostate, bladder and renal cancers. However, the effects of this polymorphism on the risk of these cancers remain conflicting. Therefore, we performed a meta-analysis to assess the association between L432V polymorphism and the susceptibility of urinary cancers. Methods We searched the PubMed database without limits on language for studies exploring the relationship of CYP1B1 L432V polymorphism and urinary cancers. Article search was supplemented by screening the references of retrieved studies manually. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the strength of these associations. Simultaneously, publication bias was estimated by funnel plot and Begg’s test with Stata 11 software. Results We observed a significant association between CYP1B1 L432V polymorphism and urinary cancers. The overall OR (95% CI) of CC versus CG was 0.937 (0.881-0.996), the overall OR (95% CI) of CC versus CG + GG was 0.942 (0.890-0.997). Furthermore, we identified reduced risk for CC versus other phenotypes in both prostate and overall urinary cancers, when studies were limited to Caucasian or Asian patients. Conclusions This meta-analysis suggests that the CYP1B1 L432V polymorphism is associated with urinary cancer risk. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3108829721231527 PMID:24913727

  12. Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies

    PubMed Central

    Martinón-Torres, Federico; Png, Eileen; Khor, Chiea Chuen; Davila, Sonia; Wright, Victoria J.; Sim, Kar Seng; Vega, Ana; Fachal, Laura; Inwald, David; Nadel, Simon; Carrol, Enitan D.; Martinón-Torres, Nazareth; Alonso, Sonia Marcos; Carracedo, Angel; Morteruel, Elvira; López-Bayón, Julio; Torre, Andrés Concha; Monge, Cristina Calvo; de Aguilar, Pilar Azcón González; Torné, Elisabeth Esteban; Martínez-Padilla, María del Carmen; Martinón-Sánchez, José María; Levin, Michael; Hibberd, Martin L.; Salas, Antonio; Gómez-Carballa, Alberto; Cebey, Miriam; Sánchez, Natalia García; Calle, Irene Rivero; Grande, Antonio Justicia; Pardo-Seco, Jacobo; Barral-Arca, Ruth; Pischedda, Sara; Currás-Tuala, María-José; Rodriguez-Tenreiro, Carmen; Redondo-Collazo, Lorenzo; Sánchez, Fernanda Pardo; de la Cruz Moreno, Jesús; Millán Miralles, Mª. Leticia; García Rodríguez, José Luis; García, Susana Rey; Doce, Ana Hurtado; Barba, Ángela Ferrer; Pallares, Manuel Ortiz; Romero, Alfredo Reparaz; Muñoz Bonet, Juan Ignacio; Cancela, Manuel Silveira; Bergara, Eider Oñate; Arriortua, Amaya Bustinza; Navarro Gómez, María Luisa; Fernández, Mario Sánchez; Martínez, Xavier Allué; Ortega, Álvaro Castellanos; Rosso, Servando Pantoja; Caballero Macarrón, César Pérez; Menchón, Natalia Molini; Sánchez, Francisco Giménez; Garzón, Manuel González-Ripoll; García, María del Mar Ballesteros; Sánchez Granados, José Manuel; Ayestarán, Olga Serrano; Payo, Roman; Palazón, Sonia Cañadas; León León, Maria Cruz; Dominguez, Susana Reyes; Villanueba, David Arjona; Alonso Martín, J. Antonio; Orayen, Concepción Goñi; Iturbe, Enrique Bernaola; Alonso Salas, María Teresa; Fernández, Isabel Quintela; Booy, Robert; Coin, Lachlan J. M.; Eleftherohorinou, Hariklia; Faust, Saul; Galassini, Rachel; Habibi, Parviz; Haralambous, Elene; Kroll, Simon; Langford, Paul; Pathan, Nazima; Pollard, Andrew J.; Abdulla, Farhana; Agapow, Paul; Bellos, Evangelos; Hamilton, Shea; Herberg, Jethro A.; Hoggart, Clive; Kaforou, Myrsini; Mashbat, Meg; Mustafa, Sobia; Sancho-Shimizu, Vanessa

    2016-01-01

    Meningococcal disease (MD) remains an important infectious cause of life threatening infection in both industrialized and resource poor countries. Genetic factors influence both occurrence and severity of presentation, but the genes responsible are largely unknown. We performed a genome-wide association study (GWAS) examining 5,440,063 SNPs in 422 Spanish MD patients and 910 controls. We then performed a meta-analysis of the Spanish GWAS with GWAS data from the United Kingdom (combined cohorts: 897 cases and 5,613 controls; 4,898,259 SNPs). The meta-analysis identified strong evidence of association (P-value ≤ 5 × 10−8) in 20 variants located at the CFH gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR) = 0.62, 95% confidence interval (C.I.) = 0.52–0.73; P-value = 9.62 × 10−9). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR = 0.64, 95% C.I.) = 0.55–0.76, P-value = 3.25 × 10−8). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of CFH with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease. PMID:27805046

  13. The Association Between Metabolic Syndrome and Characteristics of Benign Prostatic Hyperplasia: A Systematic Review and Meta-Analysis.

    PubMed

    Wang, Jian-Ye; Fu, Yan-Yan; Kang, De-Ying

    2016-05-01

    The purpose of this systematic review was to examine the association of metabolic syndrome (MS) with measures of benign prostatic hyperplasia (BPH) including prostate growth rate, prostate volume, International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) level, and maximal flow rate.Medline, Cochrane CENTRAL, EMBASE, CBM, and Google Scholar databases were searched until March 23, 2015 using combinations of the keywords benign prostate hyperplasia/BPH, metabolic syndrome, total prostate volume, prostate growth rate, prostate specific antigen, International Prostate Symptom Score/IPSS, maximal flow rate. Cohort or case-control studies of patients with BPH and MS that reported quantitative outcomes were included. The pooled mean differences of the outcome measures were compared between patients with and without MS.A total of 158 potentially relevant studies were identified, and 8 were included in the meta-analysis. The 8 studies included in the meta-analysis contained a total of 3093 BPH patients, wherein 1241 had MS and 1852 did not have MS. BPH patients with MS had a significantly higher prostate growth rate (pooled mean difference = 0.67 mL/y, P < 0.001) and larger prostate volume (pooled mean difference = 6.8 mL, P = 0.010) than the BPH patients without MS. There was no significant difference in IPSS score (pooled mean difference = 1.58, P = 0.202) or maximal flow rate (pooled mean difference = -1.41 mL/s, P = .345) between BPH patients with and without MS. A borderline nonsignificant difference in PSA (pooled mean difference = 0.24 ng/mL, P = 0.056) was noted between BPH patients with and without MS.The results of this meta-analysis are consistent with literature indicating that BPH patients with MS have a higher prostate growth rate and larger prostate volume than those without MS; however, further study is necessary to determine the association of BPH and metabolic disorder elements and the

  14. Association between COX-2 -1195G>A polymorphism and gastrointestinal cancer risk: A meta-analysis

    PubMed Central

    Zhang, Xiao-Wei; Li, Jun; Jiang, Yu-Xing; Chen, Yu-Xiang

    2017-01-01

    AIM To perform a meta-analysis to investigate the association between cyclooxygenase-2 (COX-2) -1195G>A gene polymorphism and gastrointestinal cancers. METHODS Publications related to the COX-2 -1195G>A gene polymorphism and gastrointestinal cancers published before July 2016 were retrieved from PubMed, EMBASE, Web of Science, China Biological Medicine Database, China National Knowledge Infrastructure, and CQVIP Database. Meta-analysis was performed using Stata11.0 software. The strength of the association was evaluated by calculating the combined odds ratios (ORs) and the corresponding 95%CIs. The retrieved publications were excluded or included one by one for sensitivity analysis. In addition, the funnel plot, Begg’s rank correlation test, and Egger’s linear regression method were applied to analyse whether the included publications had publication bias. RESULTS A total of 24 publications related to the COX-2 -1195G>A gene polymorphism were included, including 28 studies involving 11043 cases and 18008 controls. The meta-analysis results showed that the COX-2 -1195G>A gene polymorphism significantly correlated with an increased risk of gastrointestinal cancers, particularly gastric cancer (A vs G: OR = 1.35; AA/AG vs GG: OR = 1.54; AA vs GG/AG: OR = 1.43; AA vs GG: OR = 1.80; AG vs GG: OR = 1.35). Compared to the Caucasian population in America and Europe, the COX-2 -1195G>A gene polymorphism in the Asian population (A vs G: OR = 1.30; AA/AG vs GG: OR = 1.50; AA vs GG/AG: OR = 1.35; AA vs GG: OR = 1.71; AG vs GG: OR = 1.37) significantly increased gastrointestinal cancer risk. The sensitivity analysis (P < 0.05) and the false positive report probability (P < 0.2) confirmed the reliability of the results. CONCLUSION The results showed that the COX-2 -1195G>A gene polymorphism might be a potential risk factor for gastrointestinal cancers. Further validation by a large homogeneous study is warranted.

  15. Nestin Expression Is Associated with Poor Clinicopathological Features and Prognosis in Glioma Patients: an Association Study and Meta-analysis.

    PubMed

    Lv, Donglai; Lu, Lin; Hu, Zongtao; Fei, Zhenle; Liu, Meiqin; Wei, Lei; Xu, Jun

    2017-01-01

    Nestin has been identified as a molecular marker of neural progenitor cells and putative glioma stem cells (GSCs). Various studies examining the relationship between nestin expression with the clinical outcome in glioma patients have yielded inconclusive results. Thus, we conducted a systematic review to evaluate the association of nestin with prognosis and clinicopathological features of glioma patients. The electronic searches were performed through the database of PubMed, MEDLINE, Embase, and CNKI. In total, this meta-analysis included 14 studies covering 897 nestin + cases and 704 controls. The correlation between nestin expression and clinicopathological or prognostic parameters was evaluated by Stata 11.0 software. Our results showed that nestin protein abundance was significantly correlated with the histological grade [odds ratio (OR) = 4.36, 95 % confidence interval (CI) = 2.14-8.88, P = 0.003] of glioma. With respect to prognosis, nestin expression was positively correlated with overall survival (OS) [hazard ratio (HR) = 1.98, 95 % CI = 1.30-3.02, P = 0.000] and progression-free survival (PFS) (HR = 1.90, 95 % CI = 1.18-3.07, P = 0.040). The further stratified analysis not only defined the predictive function of nestin in different ages but also revealed that different antibodies did not alter the positive outcomes and higher standard cutoff values were more suitable for the accurate assay of nestin. Taken together, our results indicate that nestin may play an important role in the prediction of the clinicopathology and poor prognosis of glioma patients. This study should be taken into consideration in the development of new diagnostic and therapeutic programs.

  16. A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants

    PubMed Central

    Theodoratou, E; Campbell, H; Tenesa, A; Houlston, R; Webb, E; Lubbe, S; Broderick, P; Gallinger, S; Croitoru, E M; Jenkins, M A; Win, A K; Cleary, S P; Koessler, T; Pharoah, P D; Küry, S; Bézieau, S; Buecher, B; Ellis, N A; Peterlongo, P; Offit, K; Aaltonen, L A; Enholm, S; Lindblom, A; Zhou, X-L; Tomlinson, I P; Moreno, V; Blanco, I; Capellà, G; Barnetson, R; Porteous, M E; Dunlop, M G; Farrington, S M

    2010-01-01

    Background: Defective DNA repair has a causal role in hereditary colorectal cancer (CRC). Defects in the base excision repair gene MUTYH are responsible for MUTYH-associated polyposis and CRC predisposition as an autosomal recessive trait. Numerous reports have suggested MUTYH mono-allelic variants to be low penetrance risk alleles. We report a large collaborative meta-analysis to assess and refine CRC risk estimates associated with bi-allelic and mono-allelic MUTYH variants and investigate age and sex influence on risk. Methods: MUTYH genotype data were included from 20 565 cases and 15 524 controls. Three logistic regression models were tested: a crude model; adjusted for age and sex; adjusted for age, sex and study. Results: All three models produced very similar results. MUTYH bi-allelic carriers demonstrated a 28-fold increase in risk (95% confidence interval (CI): 6.95–115). Significant bi-allelic effects were also observed for G396D and Y179C/G396D compound heterozygotes and a marginal mono-allelic effect for variant Y179C (odds ratio (OR)=1.34; 95% CI: 1.00–1.80). A pooled meta-analysis of all published and unpublished datasets submitted showed bi-allelic effects for MUTYH, G396D and Y179C (OR=10.8, 95% CI: 5.02–23.2; OR=6.47, 95% CI: 2.33–18.0; OR=3.35, 95% CI: 1.14–9.89) and marginal mono-allelic effect for variants MUTYH (OR=1.16, 95% CI: 1.00–1.34) and Y179C alone (OR=1.34, 95% CI: 1.01–1.77). Conclusions: Overall, this large study refines estimates of disease risk associated with mono-allelic and bi-allelic MUTYH carriers. PMID:21063410

  17. A systematic review and meta-analysis of the association between the apolipoprotein E genotype and delirium.

    PubMed

    Adamis, Dimitrios; Meagher, David; Williams, John; Mulligan, Owen; McCarthy, Geraldine

    2016-04-01

    The role of apolipoprotein E (APOE) in Alzheimer's disease and other dementias has been investigated intensively. However, the relationship between APOE and delirium has only recently been explored in studies that have included relatively small samples. A meta-analysis of the published pooled data is timely to explore the relationship between APOE and delirium and to inform further research in this topic. PubMed, EBSCOhost, Google Scholar, Scopus, all EBM Reviews (OVID) and the Cochrane Database of Systematic Reviews were searched with relevant keywords and from the references of relevant papers. Ten papers were found that examined the relationship between APOE and delirium. Data were extracted from eight of them and pooled for meta-analysis using random effects with R software. Data from 1762 participants, of whom 479 (27.2%) were diagnosed with delirium, showed low heterogeneity (Q=13.11, d.f.=7, P=0.07; I=44.86%). The possession of the APOE ε4 allele has a small (log odds ratio: 0.18, 95% confidence interval: 0.23-0.59), nonsignificant (P=0.38) effect on the presence of delirium. No publication bias was identified. The metapower of the pooled data was low (α=0.05, power=0.65). On analysing the studies to date, it seems that there is no association between APOE and the occurrence of delirium. We suggest that further studies are needed with greater number of patients to clarify any association as well as to examine for other patterns of association including relevance for subgroups of patients who develop delirium and for effects on the phenotype of delirium and the outcomes.

  18. Association between Genetic Polymorphisms in Interleukin Genes and Recurrent Pregnancy Loss – A Systematic Review and Meta-Analysis

    PubMed Central

    Bao, Xiao; Niu, Wenbin; Wang, Linlin; Du, Linqing; Zhang, Nan; Sun, Yingpu

    2017-01-01

    Interleukins are a group of immunomodulatory proteins that mediate a variety of immune reactions in the human body. To investigate the association between interleukin gene polymorphisms and recurrent pregnancy loss (RPL), we reviewed 21 studies from MEDLINE, EMBASE, OVID SP and PubMed to evaluate RPL-related interleukin gene polymorphisms. Meta-analysis was performed on 12 of the polymorphisms, and a review included the others. Our integrated results indicated that IL-1β (-511C/T) (P = 0.02, 95% CI 0.77[0.62,0.96]), IL-6 (-634C/G) (P<0.001, 95% CI 2.91[2.01,4.22]), IL-10 (-1082G/A, –819T/C) (P = 0.01, 95% CI 0.80[0.67,0.96]; P<0.01, 95% CI 0.66[0.49,0.89]), and IL-18 (-137G/C, -105G/A) (P<0.01, 95% CI 1.69[1.24,2.31]; P = <0.01, 95% CI 1.41[1.17,1.70]) consistently associated with RPL after meta-analysis. IL-17A rs2275913 and IL-17F rs763780, IL-21 rs2055979 and rs13143866, IL-1β (-31C/T), IL-6 (-2954G/C), and IL-10 (-536A/G) were reported only once as having a significant association with RPL. The potential mechanism underlying miscarriage and these polymorphisms and future research directions are also discussed. PMID:28103273

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

    PubMed

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

    2014-09-01

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

  20. A meta-analysis of the association of exhaled carbon monoxide on asthma and allergic rhinitis.

    PubMed

    Shaoqing, Yu; Ruxin, Zhang; Yingjian, Chen; Jianqiu, Chen; Yanshen, Wang; Genhong, Li

    2011-08-01

    The objective of this study is to evaluate the effect of exhaled CO (eCO) on the development of asthma and allergic rhinitis (AR) by means of reviewing published literature. The literatures published between January 1997 and December 2008 from the US National Library of Medicine (NLM) Database were obtained according to inclusion criteria. Meta-analysis of randomized controlled trials (RCTs) was performed. CO levels of asthma and AR patients were compared with that of normal controls. HO-1(heme oxygenase-1) expression and effect of corticosteroids on eCO levels were also analyzed. Fifteen studies concerning asthma and four studies concerning AR were included in this analysis. Heterogeneity from different studies was evident (P < 0.0001), so a random-effects model was preferred. The meta-analysis revealed that asthmatic patients had significantly higher levels of eCO compared to normal controls. There was significant difference between asthma and control groups in terms of eCO (combined weighted mean difference (WMD) 1.33 (95% confidence interval 0.72 to 1.95), P < 0.0001), and no significant difference between AR and control (combined WMD 0.93 (95% confidence interval -0.54 to 2.40), P = 0.22). HO-1 expression were also reviewed, asthma group produced greater expression of HO-1 than control group with significant difference (combined standardized mean difference (SMD) 2.98 (95% confidence interval 1.13 to 4.84), P = 0.002). After corticosteroid therapy, significantly different levels of eCO were produced after corticosteroid therapy than did asthma group (combined WMD -1.23 (95% confidence interval -2.43 to -0.03), P = 0.04). The analysis reveals that eCO levels were significantly raised in asthma and it may attribute to high expression of HO-1, but there were no significantly high eCO levels between AR and control groups. Due to sensitivity to corticosteroid inhibition, eCO may be used as a practical marker to detect and monitor exacerbation of asthma.

  1. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis

    PubMed Central

    2014-01-01

    Background Cognitive impairment, including dementia, is a major health concern with the increasing aging population. Preventive measures to delay cognitive decline are of utmost importance. Alzheimer’s disease (AD) is the most frequent cause of dementia, increasing in prevalence from <1% below the age of 60 years to >40% above 85 years of age. Methods We systematically reviewed selected modifiable factors such as education, smoking, alcohol, physical activity, caffeine, antioxidants, homocysteine (Hcy), n-3 fatty acids that were studied in relation to various cognitive health outcomes, including incident AD. We searched MEDLINE for published literature (January 1990 through October 2012), including cross-sectional and cohort studies (sample sizes > 300). Analyses compared study finding consistency across factors, study designs and study-level characteristics. Selecting studies of incident AD, our meta-analysis estimated pooled risk ratios (RR), population attributable risk percent (PAR%) and assessed publication bias. Results In total, 247 studies were retrieved for systematic review. Consistency analysis for each risk factor suggested positive findings ranging from ~38.9% for caffeine to ~89% for physical activity. Education also had a significantly higher propensity for “a positive finding” compared to caffeine, smoking and antioxidant-related studies. Meta-analysis of 31 studies with incident AD yielded pooled RR for low education (RR = 1.99; 95% CI: 1.30-3.04), high Hcy (RR = 1.93; 95% CI: 1.50-2.49), and current/ever smoking status (RR = 1.37; 95% CI: 1.23-1.52) while indicating protective effects of higher physical activity and n-3 fatty acids. Estimated PAR% were particularly high for physical activity (PAR% = 31.9; 95% CI: 22.7-41.2) and smoking (PAR%=31.09%; 95% CI: 17.9-44.3). Overall, no significant publication bias was found. Conclusions Higher Hcy levels, lower educational attainment, and decreased physical activity were

  2. Quantitative assessment of the association between fibroblast growth factor 20 rs1721100 C/G polymorphism and the risk of sporadic Parkinson's diseases: a meta-analysis.

    PubMed

    Ma, Ze-Gang; Xu, Jian; Liu, Tian-Wei

    2015-01-01

    Fibroblast growth factor 20 (FGF20) is a neurotrophic factor which enhances the survival of rat midbrain dopamine neurons. Genetic variation in FGF20 may influence the risk of occurrence and development in Parkinson's diseases (PD). Many studies have evaluated the association between FGF20 rs1721100 C/G polymorphism and the risk of sporadic PD; however, published data are still controversial. The aim of the present meta-analysis was to evaluate the association of FGF20 rs1721100 C/G polymorphism with susceptibility of PD. The summary odds ratio (OR) with its 95 % confidence interval (CI) was calculated to estimate the association. Five case-control studies with a total of 3,463 sporadic PD cases and 4,606 controls were finally included into this meta-analysis. Neither the basic allele frequencies nor the genotypic distributions of rs1721100 C/G within FGF20 were different between two groups when all studies were pooled into the meta-analysis. Subgroup analysis by ethnicity showed FGF20 rs1721100 C/G polymorphism was significantly associated with increased risk in the heterozygote comparison model (CG versus GG: OR = 0.83, 95 % CI, 0.72-0.95, P = 0.009) in Asians but not in Caucasians. Overall, this meta-analysis suggests that FGF20 rs1721100 C/G polymorphism is associated with sporadic PD in Asians.

  3. Thromboembolic Events Associated with Bevacizumab plus Chemotherapy for Patients with Colorectal Cancer: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Alahmari, Abdullah K.; Almalki, Ziyad S.; Alahmari, Ahmed K.; Guo, Jeff J.

    2016-01-01

    studies reviewed in this meta-analysis, the risk for venous or arterial TEEs was associated with bevacizumab use in patients with CRC. Healthcare providers are encouraged to consider thromboprophylaxis agents, periodically monitor their patients who receive bevacizumab, and carefully manage patients who are at increased risk for those complications. PMID:27688834

  4. Evaluation Outcomes Associated with Alternative Dosing Strategies for Piperacillin/Tazobactam: A Systematic Review and Meta-Analysis.

    PubMed

    Yang, Hui; Cui, Xiangli; Ma, Zhuo; Liu, Lihong

    2016-01-01

    A better dosing strategy can improve clinical outcomes for patients. We systematically reviewed the literatures to determine whether any clinical benefits exist for piperacillin/tazobactam by extended or continuous infusion. Methods - A search of PubMed, Web of Science, ProQuest, ScienceDirect, Cochrane, Embase and related ICAAC and ACCP conferences were conducted up to September 5, 2015. Randomized controlled and observational studies that compared extended or continuous infusion with conventional intermittent infusion of piperacillin/tazobactam were identified from the databases above and analyzed. Two reviewers independently evaluated the methodology and extracted data from primary studies. A meta-analysis was performed using Revman 5.2 software. The quality of each study was assessed. Sensitivity analysis and publication bias were evaluated. Results - Three randomized controlled trials and twelve observational studies were included in this study. All included studies had high quality and no publication bias was found. Compared to the conventional intermittent infusion approach, the extended or continuous infusion group had a significant cost effectiveness (OR -0.89.02, CI (-114.69,-63.35), P<0.00001). No statistical difference was observed for clinical cure rate (OR 1.64, 95% CI (0.88, 3.30), P=0.12) between the two dosing regimens. The sensitivity analysis showed the results were stable. Conclusions - Our systematic review and meta-analysis found that the outcomes associated with alternative dosing strategies of piperacillin/tazobactam have changed compared with conclusions before for several literatures with large samples published. Further data on the outcomes should be generated for a better understanding of the extended or continuous infusion strategy. On the whole, our meta-analysis suggested that the extended or continuous infusion should be recommended for clinical use only considering its economic advantage, but there was no significantly higher

  5. The neutrophil lymphocyte ratio is associated with breast cancer prognosis: an updated systematic review and meta-analysis

    PubMed Central

    Wei, Bajin; Yao, Minya; Xing, Chunyang; Wang, Wei; Yao, Jia; Hong, Yun; Liu, Yu; Fu, Peifen

    2016-01-01

    Breast cancer (BC) is the most common female malignancy within the spectrum of human cancer. One promising way to reduce the mortality and morbidity of BC is to explore novel diagnostic markers for early diagnosis and prognostication. The neutrophil lymphocyte ratio (NLR) is a good reflection of inflammation, which plays an important role in tumor progression and metastasis. However, the association between NLR and BC prognosis remains unclear. The aim of this meta-analysis is to explore the prognostic value of NLR in BC. Among the screened references in the database, 12 eligible studies were identified in this study. Patients with a higher NLR had a shorter disease-free survival (hazard ratio =1.46, 95% confidence interval: 1.12–1.90, P=0.044) and overall survival (hazard ratio =2.03, 95% confidence interval: 1.41–2.93, P<0.001). In the subgroup analysis of NLR and disease-free survival, the studies from Eastern countries had a positive result with perfect homogeneity (I2=0); however, this homogeneity has not been achieved in studies from Western countries. In the subgroup analysis of the NLR and overall survival, the results of the univariate and multivariate analyses were completely different, with different heterogeneity. In the luminal A and luminal B subtypes, we found that there was no association between the NLR and overall survival in the BC patients. Positive results were obtained in the analyses of the human epidermal growth factor receptor 2 (HER2)-positive and triple-negative BC subtypes. In conclusion, this meta-analysis suggests that NLR is a good prognostic marker for BC, and patients with a higher NLR have poorer prognoses. Future studies should perform more detailed investigations to decrease heterogeneity and determine the appropriate cut-off values for different races. PMID:27660475

  6. Association between primary Sjögren's syndrome and pregnancy complications: a systematic review and meta-analysis.

    PubMed

    Upala, Sikarin; Yong, Wai Chung; Sanguankeo, Anawin

    2016-08-01

    Systemic autoimmune disorders may interfere with normal reproductive function resulting in negative outcome of pregnancy. Primary Sjögren's syndrome (pSS) is a common rheumatic disease that mostly affects females. There are many reports that this condition may increase risk of pregnancy complications and fetal loss. However, data regarding these adverse outcomes are scarce and inconclusive. We performed a systematic review and meta-analysis of available articles that assess the association between pSS and adverse pregnancy outcome. We comprehensively searched the databases of MEDLINE and EMBASE from their dates of inception to March 2016 and reviewed papers with validity criteria. A random-effects model was used to evaluate pregnancy complications in patients with pSS and healthy controls. From 20 full-text articles, 7 studies involving 544 patients and 1586 pregnancies were included in the meta-analysis. Fetal complications included spontaneous abortion, stillbirth, neonatal deaths, and intrauterine growth retardation. Compared with healthy pregnancy, patients with pSS had significantly higher chance of neonatal deaths (pooled odds ratio (OR) = 1.77, 95 % confidence interval (CI) 1.28 to 1.46, p = 0.01). However, there were no significant associations between pSS and premature birth (OR = 2.10, 95 % CI 0.59-7.46, p = 0.25), spontaneous abortion (OR = 1.46, 95 % CI 0.72-2.93, p = 0.29), artificial abortion (OR = 1.12, 95 % CI 0.52-2.61, p = 0.71), or stillbirth (OR = 1.05, 95 % CI 0.38-2.97, p = 0.92). There is an increased risk of fetal loss in pregnant patients with pSS. The presented evidence further supports multidisciplinary care for these patients to prevent complications during pregnancy.

  7. The Prognostic and Clinicopathological Significance of Tumor-Associated Macrophages in Patients with Gastric Cancer: A Meta-Analysis

    PubMed Central

    Li, Zhan; Zhang, Junyan; Luo, Jiazi; Lu, Chunyang; Xu, Hao; Xu, Huimian

    2017-01-01

    Objective Comprehensive studies have investigated the prognostic and clinicopathological value of tumor-associated macrophages (TAMs) in gastric cancer patients, yet results remain controversial. Therefore, we performed a meta-analysis to clarify this issue. Methods PubMed, Embase, and the Cochrane Library databases were searched to identify eligible studies. We extracted hazard ratios (HRs) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) to estimate the effect sizes. In addition, subgroup analysis and sensitivity analysis were also conducted. Results A total of 19 studies involving 2242 patients were included. High generalised TAMs density was significantly associated with poor overall survival (OS) (HR 1.49, 95% CI 1.15–1.95). Subgroup analysis revealed that CD68+ TAMs had no significant effect on OS (HR 1.38, 95% CI 1.00–1.91). High M1 TAMs density was correlated with better OS (HR 0.45, 95% CI 0.32–0.65). By contrast, high density of M2 TAMs was correlated with a poor prognosis for OS (HR 1.48, 95% CI 1.25–1.75). Furthermore, high M2 TAMs density was correlated with larger tumor size, diffuse Lauren type, poor histologic differentiation, deeper tumor invasion, lymph node metastasis, and advanced TNM stage. Conclusions Overall, this meta-analysis reveal that although CD68+ TAMs infiltration has the neutral prognostic effects on OS, the M1/M2 polarization of TAMs are predicative factor of prognosis in gastric cancer patients. PMID:28081243

  8. Association of MCP-1-2518A/G polymorphism with susceptibility to autoimmune diseases: a meta-analysis.

    PubMed

    Chen, Si; Deng, Chuiwen; Hu, Chaojun; Li, Jing; Wen, Xiaoting; Wu, Ziyan; Li, Yuan; Zhang, Fengchun; Li, Yongzhe

    2016-05-01

    We performed a meta-analysis to estimate whether combined evidence shows the association between the MCP-1-2518A/G polymorphism and susceptibility to autoimmune diseases. Relevant articles dated to July 2014 were acquired from the PubMed, EMBASE, ISI, and CNKI databases. The number of the genotypes and/or alleles for the MCP-1-2518A/G in cases and control subjects was extracted, and statistical analysis was conducted using STATA 11.2 software. Summary odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) were used to calculate the risk of autoimmune diseases with the MCP-1-2518A/G. Significant increased risk of autoimmune diseases could be found for A allele vs. G allele (OR = 1.616, 95 % CI 1.027-2.542, P = 0.038) and AA + AG vs. GG (OR = 1.616, 95 % CI 1.027-2.542, P = 0.038) in Asian patients with rheumatoid arthritis (RA), and for A allele vs. G allele (OR = 1.383, 95 % CI 1.142-1.676, P = 0.022) and AA vs. AG + GG (OR = 1.575, 95 % CI 1.361-1.823, P < 0.001) in European patients with Crohn's disease (CD). In addition, when comparison of European patients with lupus nephritis (LN) and without LN, significant association between patients with LN and without LN also could be found for AA vs. AG + GG (OR = 0.713, 95 % CI 0.545-0.933, P = 0.014). This meta-analysis showed that the MCP-1-2518-A allele confers susceptibility to Asian patients with RA and European patients with CD.

  9. Association between the methylenetetrahydrofolate reductase c.677C>T polymorphism and bone mineral density: an updated meta-analysis.

    PubMed

    Li, Hong-Zhuo; Wang, Wei; Liu, Yi-Ling; He, Xiao-Feng

    2016-02-01

    Many studies have reported an association between the methylenetetrahydrofolate reductase (MTHFR) c.677C>T polymorphism and reduced bone mineral density (BMD), but results have been inconsistent. We, therefore, performed a meta-analysis to further explore this association. Twenty-one studies, comprising 33,045 subjects, analyzed the association of MTHFR c.677C>T with femoral neck BMD. Significant association with reduced BMD was observed in Caucasians (recessive model: WMD = -0.004 g/cm(2), 95 % CI -0.008 to -0.006), post-menopausal women (recessive model: WMD = -0.005 g/cm(2), 95 % CI -0.007 to -0.003), men (dominant model: WMD = -0.004 g/cm(2), 95 % CI -0.005 to -0.004; recessive model: WMD = -0.004 g/cm(2), 95 % CI -0.005 to -0.004; TT vs. CC: WMD = -0.006 g/cm(2), 95 % CI -0.006 to -0.006; CT vs. CC: WMD = -0.003 g/cm(2), 95 % CI -0.003 to -0.003), and cohort studies (recessive model: WMD = -0.003 g/cm(2), 95 % CI -0.006 to -0.001). Twenty-two studies, which included 32,271 subjects, analyzed the MTHFR c.677C>T association with lumbar spine BMD. Significant association with reduced BMD was observed in Caucasians, women, post-menopausal women, men, and cohort studies. Seven studies, comprising 6806 subjects, analyzed the MTHFR c.677C>T association with total hip BMD, but no significant association was observed in any population. Nine studies involving 5591 subjects analyzed the association with total body BMD. Significant association with reduced BMD was observed in overall and women subgroup analyses. In summary, this meta-analysis indicates that the MTHFR c.677C>T polymorphism is associated with reduced BMD in lumbar spine and femoral neck in Caucasians, post-menopausal women, and men, and with total body BMD in women. In addition, our results suggest that new studies examining the association between MTHFR c.677C>T polymorphism and BMD of lumbar spine and femoral neck in Asians is warranted, because I (2) > 75.0 % was observed.

  10. Lack of an association between XRCC2 R188H polymorphisms and breast cancer: an update meta-analysis involving 35,422 subjects

    PubMed Central

    Kong, Bin; Lv, Zhi-Dong; Chen, Li; Shen, Ruo-Wu; Jin, Li-Ying; Yang, Zhao-Chuan

    2015-01-01

    Purpose: Several studies have investigated the associations between XRCC2 R188H polymorphism and the susceptibility to breast cancer, but the results have been inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Methods: PubMed and China National Knowledge Infrastructure (CNKI) searches were carried out for relevant studies published before March 2015. Meta-analysis was performed with the Stata, version 11.0. Results: A total of 17 case-control studies, including 17,986 cases and 17,436 controls, were selected. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygous model, dominant model, and recessive model. When all the studies were pooled into the meta-analysis, there was no evidence showing a significant association between XRCC2 R188H polymorphism and breast cancer risk (for homozygous model, OR=0.84, 95% CI=0.62-1.14; for dominant model: OR=0.76, 95% CI=0.53-1.09; and for recessive model: OR=1.04, 95% CI=0.98-1.10). In the subgroup analysis by ethnicity, no significant association was found between the polymorphism and breast cancer risk. Conclusions: In conclusion, this meta-analysis indicates that the XRCC2 R188H polymorphism is not a risk factor for developing of breast cancer. PMID:26629080

  11. GSTM1 null genotype may be associated with an increased nasopharyngeal cancer risk in South China: an updated meta-analysis and review

    PubMed Central

    Li, Yanni; Wan, Wuhanhui; Li, Ting; Cao, Jing; Xu, Ge

    2015-01-01

    Although many epidemiologic studies investigated the GSTM1 gene polymorphism and its association with nasopharyngeal carcinoma (NPC) in Chinese, definite conclusions cannot be drawn. To assess the impact of of GSTM1 polymorphism on the risk of NPC, an updated meta-analysis was performed in a Chinese population. A total of nine studies including 1,291 cases and 2,135 controls were involved in this meta-analysis. Meta-analysis of those nine studies showed that GSTM1 null genotype was associated with an increased risk of NPC in South China (odds ratio [OR] =1.47, 95% confidence interval [CI]: 1.27–1.70). In subgroup analyses stratified by source of controls, it revealed significant results in population-based studies (OR =1.40, 95% CI: 1.19–1.64). Additionally, a significant association was found in smokers (OR =3.16, 95% CI: 1.76–5.67). This meta-analysis indicated a marked association of GSTM1 with NPC risk in South China, and there might be an interaction between the polymorphism and smoking on NPC. However, further studies with gene–gene and gene–environment interactions are required for definite conclusions. PMID:26392774

  12. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

    PubMed Central

    Zeggini, Eleftheria; Scott, Laura J.; Saxena, Richa; Voight, Benjamin F.; Marchini, Jonathan L; Hu, Tainle; de Bakker, Paul IW; Abecasis, Gonçalo R; Almgren, Peter; Andersen, Gitte; Ardlie, Kristin; Boström, Kristina Bengtsson; Bergman, Richard N; Bonnycastle, Lori L; Borch-Johnsen, Knut; Burtt, Noël P; Chen, Hong; Chines, Peter S; Daly, Mark J; Deodhar, Parimal; Ding, Charles; Doney, Alex S F; Duren, William L; Elliott, Katherine S; Erdos, Michael R; Frayling, Timothy M; Freathy, Rachel M; Gianniny, Lauren; Grallert, Harald; Grarup, Niels; Groves, Christopher J; Guiducci, Candace; Hansen, Torben; Herder, Christian; Hitman, Graham A; Hughes, Thomas E; Isomaa, Bo; Jackson, Anne U; Jørgensen, Torben; Kong, Augustine; Kubalanza, Kari; Kuruvilla, Finny G; Kuusisto, Johanna; Langenberg, Claudia; Lango, Hana; Lauritzen, Torsten; Li, Yun; Lindgren, Cecilia M; Lyssenko, Valeriya; Marvelle, Amanda F; Meisinger, Christa; Midthjell, Kristian; Mohlke, Karen L; Morken, Mario A; Morris, Andrew D; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Palmer, Colin NA; Payne, Felicity; Perry, John RB; Pettersen, Elin; Platou, Carl; Prokopenko, Inga; Qi, Lu; Qin, Li; Rayner, Nigel W; Rees, Matthew; Roix, Jeffrey J; Sandbæk, Anelli; Shields, Beverley; Sjögren, Marketa; Steinthorsdottir, Valgerdur; Stringham, Heather M; Swift, Amy J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Timpson, Nicholas J; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Walker, Mark; Watanabe, Richard M; Weedon, Michael N; Willer, Cristen J; Illig, Thomas; Hveem, Kristian; Hu, Frank B; Laakso, Markku; Stefansson, Kari; Pedersen, Oluf; Wareham, Nicholas J; Barroso, Inês; Hattersley, Andrew T; Collins, Francis S; Groop, Leif; McCarthy, Mark I; Boehnke, Michael; Altshuler, David

    2009-01-01

    Genome-wide association (GWA) studies have identified multiple new genomic loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)1-11. Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to discover loci at which common alleles have modest effects, we performed meta-analysis of three T2D GWA scans encompassing 10,128 individuals of European-descent and ~2.2 million SNPs (directly genotyped and imputed). Replication testing was performed in an independent sample with an effective sample size of up to 53,975. At least six new loci with robust evidence for association were detected, including the JAZF1 (p=5.0×10−14), CDC123/CAMK1D (p=1.2×10−10), TSPAN8/LGR5 (p=1.1×10−9), THADA (p=1.1×10−9), ADAMTS9 (p=1.2×10−8), and NOTCH2 (p=4.1×10−8) gene regions. The large number of loci with relatively small effects indicates the value of large discovery and follow-up samples in identifying additional clues about the inherited basis of T2D. PMID:18372903

  13. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.

    PubMed

    Zeggini, Eleftheria; Scott, Laura J; Saxena, Richa; Voight, Benjamin F; Marchini, Jonathan L; Hu, Tianle; de Bakker, Paul I W; Abecasis, Gonçalo R; Almgren, Peter; Andersen, Gitte; Ardlie, Kristin; Boström, Kristina Bengtsson; Bergman, Richard N; Bonnycastle, Lori L; Borch-Johnsen, Knut; Burtt, Noël P; Chen, Hong; Chines, Peter S; Daly, Mark J; Deodhar, Parimal; Ding, Chia-Jen; Doney, Alex S F; Duren, William L; Elliott, Katherine S; Erdos, Michael R; Frayling, Timothy M; Freathy, Rachel M; Gianniny, Lauren; Grallert, Harald; Grarup, Niels; Groves, Christopher J; Guiducci, Candace; Hansen, Torben; Herder, Christian; Hitman, Graham A; Hughes, Thomas E; Isomaa, Bo; Jackson, Anne U; Jørgensen, Torben; Kong, Augustine; Kubalanza, Kari; Kuruvilla, Finny G; Kuusisto, Johanna; Langenberg, Claudia; Lango, Hana; Lauritzen, Torsten; Li, Yun; Lindgren, Cecilia M; Lyssenko, Valeriya; Marvelle, Amanda F; Meisinger, Christa; Midthjell, Kristian; Mohlke, Karen L; Morken, Mario A; Morris, Andrew D; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Palmer, Colin N A; Payne, Felicity; Perry, John R B; Pettersen, Elin; Platou, Carl; Prokopenko, Inga; Qi, Lu; Qin, Li; Rayner, Nigel W; Rees, Matthew; Roix, Jeffrey J; Sandbaek, Anelli; Shields, Beverley; Sjögren, Marketa; Steinthorsdottir, Valgerdur; Stringham, Heather M; Swift, Amy J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Timpson, Nicholas J; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Walker, Mark; Watanabe, Richard M; Weedon, Michael N; Willer, Cristen J; Illig, Thomas; Hveem, Kristian; Hu, Frank B; Laakso, Markku; Stefansson, Kari; Pedersen, Oluf; Wareham, Nicholas J; Barroso, Inês; Hattersley, Andrew T; Collins, Francis S; Groop, Leif; McCarthy, Mark I; Boehnke, Michael; Altshuler, David

    2008-05-01

    Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.

  14. Is there an association between aircraft noise exposure and the incidence of hypertension? A meta-analysis of 16784 participants

    PubMed Central

    Huang, Di; Song, XuPing; Cui, Qi; Tian, Jinhui; Wang, Quan; Yang, Kehu

    2015-01-01

    To determine if aircraft noise exposure causes an increased incidence of hypertension among residents near airports. We conducted a meta-analysis of observational studies to evaluate the association between aircraft noise exposure and the incidence of hypertension. PubMed, Embase, Web of Science, the Cochrane Library, and the Chinese Biomedical Literature Database were searched without any restrictions. Odds ratios (ORs) with 95% confidence intervals (CIs) were extracted. The pooled ORs were calculated using both the fixed effects model and random effects model. All analyses were performed using STATA version 12.0 software (Stata Corporation, College Station, TX, USA). We examined five studies, comprising a total of 16,784 residents. The overall OR for hypertension in residents with aircraft noise exposure was 1.63 (95% CI, 1.14-2.33), and one of our included studies showed that there was no evidence that aircraft noise is a risk factor for hypertension in women. According to our subgroup analysis, the summary OR for the incidence was 1.31 (95% CI, 0.85-2.02) with I2 of 80.7% in women and 1.36 (95% CI, 1.15-1.60) with moderate heterogeneity in men. The pooled OR for the incidence of hypertension in residents aged over 55 years and under 55 years was 1.66 (95% CI, 1.21-2.27) with no heterogeneity and 1.78 (95% CI, 1.33-2.39) with I2 of 29.4%, respectively. The present meta-analysis suggests that aircraft noise could contribute to the prevalence of hypertension, but the evidence for a relationship between aircraft noise exposure and hypertension is still inconclusive because of limitations in study populations, exposure characterization, and adjustment for important confounders. PMID:25774612

  15. Is there an association between aircraft noise exposure and the incidence of hypertension? A meta-analysis of 16784 participants.

    PubMed

    Huang, Di; Song, XuPing; Cui, Qi; Tian, Jinhui; Wang, Quan; Yang, Kehu

    2015-01-01

    To determine if aircraft noise exposure causes an increased incidence of hypertension among residents near airports. We conducted a meta-analysis of observational studies to evaluate the association between aircraft noise exposure and the incidence of hypertension. PubMed, Embase, Web of Science, the Cochrane Library, and the Chinese Biomedical Literature Database were searched without any restrictions. Odds ratios (ORs) with 95% confidence intervals (CIs) were extracted. The pooled ORs were calculated using both the fixed effects model and random effects model. All analyses were performed using STATA version 12.0 software (Stata Corporation, College Station, TX, USA). We examined five studies, comprising a total of 16,784 residents. The overall OR for hypertension in residents with aircraft noise exposure was 1.63 (95% CI, 1.14-2.33), and one of our included studies showed that there was no evidence that aircraft noise is a risk factor for hypertension in women. According to our subgroup analysis, the summary OR for the incidence was 1.31 (95% CI, 0.85-2.02) with I2 of 80.7% in women and 1.36 (95% CI, 1.15-1.60) with moderate heterogeneity in men. The pooled OR for the incidence of hypertension in residents aged over 55 years and under 55 years was 1.66 (95% CI, 1.21-2.27) with no heterogeneity and 1.78 (95% CI, 1.33-2.39) with I2 of 29.4%, respectively. The present meta-analysis suggests that aircraft noise could contribute to the prevalence of hypertension, but the evidence for a relationship between aircraft noise exposure and hypertension is still inconclusive because of limitations in study populations, exposure characterization, and adjustment for important confounders.

  16. Association between body mass index and prognosis of colorectal cancer: a meta-analysis of prospective cohort studies.

    PubMed

    Lee, Junga; Meyerhardt, Jeffrey A; Giovannucci, Edward; Jeon, Justin Y

    2015-01-01

    Studies have reported conflicting results on the association between body mass index (BMI) and prognosis of colorectal cancer. Therefore, we have conducted a meta-analysis of prospective studies, which examined the association of pre- and post-diagnostic BMI with colorectal cancer-specific mortality and all-cause mortality in patients with colorectal cancer. We searched Medline and EMBASE database published between 1970 and September 2014. A total of 508 articles were identified, of which 16 prospective cohort studies were included for the current meta-analysis. The analysis included 58,917 patients who were followed up over a period ranging from 4.9 to 20 years (median: 9.9 years). We found that being underweight before cancer diagnosis was associated with increased all-cause mortality (Relative risk [RR]: 1.63, 95% CI: 1.18-2.23, p < 0.01) and being obese (BMI ≥ 30 kg/m(2)) before cancer diagnosis was associated with increased colorectal cancer-specific mortality (RR: 1.22, 95% CI: 1.003-1.35, p < 0.01) and all-cause mortality (RR: 1.25, 95% CI: 1.14-1.36, p < 0.01). On the other hand, being underweight (RR: 1.33, 95% CI: 1.20-1.47, p < 0.01), obese (RR: 1.08, 95% CI: 1.03-1.3, p < 0.01), and class II/III obese (BMI ≥ 35 kg/m(2); RR: 1.13, 95% CI: 1.04-1.23, p < 0.01) after diagnosis were associated with significantly increased all-cause mortality. Being obese prior to diagnosis of colorectal cancer was associated with increased colorectal cancer-specific mortality and all-cause mortality, whereas being obese after diagnosis was associated with increased all-cause mortality. The associations with being underweight may reflect reverse causation. Maintaining a healthy body weight should be discussed with colorectal cancer survivors.

  17. Metamizole-Associated Adverse Events: A Systematic Review and Meta-Analysis

    PubMed Central

    Fässler, Margrit; Blozik, Eva; Linde, Klaus; Jüni, Peter; Reichenbach, Stephan; Scherer, Martin

    2015-01-01

    Background Metamizole is used to treat pain in many parts of the world. Information on the safety profile of metamizole is scarce; no conclusive summary of the literature exists. Objective To determine whether metamizole is clinically safe compared to placebo and other analgesics. Methods We searched CENTRAL, MEDLINE, EMBASE, CINAHL, and several clinical trial registries. We screened the reference lists of included trials and previous systematic reviews. We included randomized controlled trials that compared the effects of metamizole, administered to adults in any form and for any indication, to other analgesics or to placebo. Two authors extracted data regarding trial design and size, indications for pain medication, patient characteristics, treatment regimens, and methodological characteristics. Adverse events (AEs), serious adverse events (SAEs), and dropouts were assessed. We conducted separate meta-analyses for each metamizole comparator, using standard inverse-variance random effects meta-analysis to pool the estimates across trials, reported as risk ratios (RRs). We calculated the DerSimonian and Laird variance estimate T2 to measure heterogeneity between trials. The pre-specified primary end point was any AE during the trial period. Results Of the 696 potentially eligible trials, 79 trials including almost 4000 patients with short-term metamizole use of less than two weeks met our inclusion criteria. Fewer AEs were reported for metamizole compared to opioids, RR = 0.79 (confidence interval 0.79 to 0.96). We found no differences between metamizole and placebo, paracetamol and NSAIDs. Only a few SAEs were reported, with no difference between metamizole and other analgesics. No agranulocytosis or deaths were reported. Our results were limited by the mediocre overall quality of the reports. Conclusion For short-term use in the hospital setting, metamizole seems to be a safe choice when compared to other widely used analgesics. High-quality, adequately sized

  18. Mortality and complications associated with laparoscopic cholecystectomy. A meta-analysis.

    PubMed Central

    Shea, J A; Healey, M J; Berlin, J A; Clarke, J R; Malet, P F; Staroscik, R N; Schwartz, J S; Williams, S V

    1996-01-01

    OBJECTIVE: The purpose of this study was to perform a meta-analysis of large laparoscopic cholecystectomy case-series and compare results concerning complications, particularly bile duct injury, to those reported in open cholecystectomy case-series. SUMMARY BACKGROUND DATA: Since the introduction of laparoscopic cholecystectomy in the United States, hundreds of reports about the technique have been published, many including statements about the advantages of laparoscopic cholecystectomy compared with those of open cholecystectomy. There is an unevenness in scope and quality of the studies. Nevertheless, enough data have accumulated from large series to permit analyses of data regarding some of the most important issues. METHODS: Articles identified via a MEDLINE (the National Library of Medicine's computerized database) search were evaluated according to standard criteria. Data regarding the patient sample, study methods, and outcomes of cholecystectomy were abstracted and summarized across studies. RESULTS: Outcomes of laparoscopic cholecystectomy are examined for 78,747 patients reported on in 98 studies and compared with outcomes of open cholecystectomy for 12,973 patients reported on in 28 studies. Laparoscopic cholecystectomy appears to have a higher common bile duct injury rate and a lower mortality rate. Estimated rates of other types of complications after laparoscopic cholecystectomy generally were low. Most conversions followed operative discoveries (e.g., dense adhesions) and were not the result of injury. CONCLUSIONS: There is wide variability in the amount and type of data reported within any single study, and patient populations may not be comparable across studies. Except for a higher common bile duct injury rate, laparoscopic cholecystectomy appears to be at least as safe a procedure as that of open cholecystectomy. PMID:8916876

  19. Association of anti-sperm antibodies with chronic prostatitis: A systematic review and meta-analysis.

    PubMed

    Jiang, Yumei; Cui, Dong; Du, Yuefeng; Lu, Jun; Yang, Lin; Li, Jinmei; Zhang, Jing; Bai, Xiaojing

    2016-11-01

    Chronic prostatitis is a risk factor for impaired male fertility potential, and anti-sperm antibodies (ASAs) cause the autoimmune disease immune infertility, which has a negative effect on semen parameters. Current studies have investigated the ASA-positive relationship between chronic prostatitis versus normal controls, but have shown inconsistent results. Hence, we systematic searched the PubMed, EMBASE, Science Direct/Elsevier, Medline, and the Cochrane Library up to October 2015 for case-control studies that involved the ASA-positive relationship between chronic prostatitis patients versus normal controls. The meta-analysis was performed with Review Manager and Stata software. After literature search, six studies were identified, including 721 cases of chronic prostatitis and 160 normal controls. Our results illustrated a significant correlation of the ASA-positive relationship between chronic prostatitis patients versus normal controls. The combined odds ratio of the ASA-positive rate in chronic prostatitis patients and normal controls was 3.26 (1.86-5.71). There was also a significant correlation of the ASA-positive relationship between National Institutes of Health (NIH) III versus normal controls, and the combined OR was 2.46 (1.10-5.51). However, there was no significant correlation of the ASA-positive relationship between National Institutes of Health (NIH) II versus normal controls. The present study illustrates that the positive rate of ASAs in chronic prostatitis patients was significantly higher than in the control group, suggesting that chronic prostatitis has a negative effect on male reproductive function. However, studies with larger samples are needed to better illuminate the correlation between ASAs and chronic prostatitis.

  20. Associations of polymorphisms of rs1015213 with primary angle closure glaucoma-recent evidence and a meta-analysis

    PubMed Central

    Liao, Liang; Gong, Xiaohong; Lu, Ming; Yan, Xiaoling; Xia, Yanting; Wei, Qiping

    2015-01-01

    Background: Primary angle closure glaucoma (PACG) has been thought to have a significantly genetic basis for a long time, and genome-wide association studies (GWAS) have identified various candidate genes including PCMTD1-ST18 rs1015213 as susceptibility loci. However, different results produced inconsistent results and make the conclusions controversial in some extent. Thus, we carried out a systematic review, attempting to summarize the recent evidence and determine the association of rs1015213 with PACG risk. Methods: A systematic literature search was conducted to identify all published studies on associations of rs1015213 (PCMTD1-ST18) polymorphism and PACG risk up to April 30, 2015. Selection of eligible studies was undertaken by two investigators according to inclusion criteria. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs), as well as the pooled ocular biometric measures in different genotype or allele groups, were collected and analyzed. Heterogeneity was measured using the chi-square-based Q statistic test and I2 metric. Publication bias of the included articles was evaluated using funnel plots. Results: 21 eligible studies were included, among them 15 studies with enough data to estimate OR were included for meta-analysis, with a total of 24764 subjects (4737 PACG patients and 20027 controls), including 19416 Asian subjects (4378 PACG patients and 15038 controls) and 5348 Caucasian subjects (359 PACG patients and 4989 controls). Low heterogeneity was detected among studies (for Asian subgroups P=0.80, I2=0%, for Caucasian subgroups P=0.78, I2=0%, for all groups, P=0.89, I2=0%), thus, only fixed-effects model was used in the meta-analysis. The results showed that the frequencies of the TT genotype of rs1015213 were significant higher in PACG group than the controls in Asians (OR=1.51, 95% CI 1.27-1.79, P<0.01) but not in Caucasians (OR=1.54, 95% CI 0.94-2.54, P=0.09). In sensitivity analysis the significance of the pooled OR remained

  1. Children's exposure to intimate partner violence: A meta-analysis of longitudinal associations with child adjustment problems.

    PubMed

    Vu, Nicole L; Jouriles, Ernest N; McDonald, Renee; Rosenfield, David

    2016-06-01

    This meta-analysis reviewed 74 studies that examined longitudinal associations between children's exposure to intimate partner violence (IPV) and their adjustment problems. Results indicated that children's exposure to IPV is linked prospectively with child externalizing, internalizing, and total adjustment problems. Moreover, the magnitude of the association between IPV exposure and child externalizing and internalizing problems strengthens over time. In addition, associations are stronger between IPV exposure and child externalizing and internalizing problems when IPV is conceptualized broadly rather than narrowly (physical IPV+psychological and/or sexual IPV versus physical IPV only), and when information on IPV and child adjustment problems is obtained from the same source, rather than independent sources. When IPV exposure is measured at younger ages, compared to older ages, the association between IPV and child externalizing problems is greater. However, when child adjustment problems are measured at older ages, compared to younger ages, the association between IPV and child internalizing problems is greater. Child sex, sample type, and whether only the male partner's violence or both partners' violence was measured did not predict the association between children's exposure to IPV and later adjustment problems. The findings have both research and clinical implications regarding the long-term adjustment of children exposed to IPV and the conceptualization and measurement of resilience subsequent to IPV.

  2. Association of Common Variants in eNOS Gene with Primary Open Angle Glaucoma: A Meta-Analysis

    PubMed Central

    Xiang, Yang; Dong, Yi; Li, Xuan; Tang, Xin

    2016-01-01

    Purpose. To clarify the association of endothelial nitric oxide synthase (eNOS) polymorphisms and primary open angle glaucoma (POAG). Methods. After a systematic literature search in the MEDLINE, EMBASE, and ISI Web of Science databases, all relevant studies evaluating the association between the polymorphisms (rs2070744 and rs1799983) of eNOS gene and POAG were screened and included. The pooled odds ratios (ORs) and the 95% confidence interval (CI) of each single-nucleotide polymorphism (SNP) in five genetic models were estimated using fixed-effect model if I2 < 50% in the test for heterogeneity; otherwise the random-effects model was used. Results. Thirty-one records were obtained, with five being suitable for meta-analysis. The overall results showed that both TT genotype in rs2070744 and GG genotype in rs1799983 are associated with decreased risk of POAG susceptibility. Stratified analysis based on ethnicity showed that the association of rs2070744 with POAG remained only in Caucasians. Results of subgroup analysis by sex indicated association between both polymorphisms and POAG in female group, but not in male group. Conclusions. TT genotype and/or T-allele in rs2070744, as well as GG genotype and/or G-allele in rs1799983, was associated with decreased risk for POAG overall and in female group. PMID:27242919

  3. Association between Genetic Variants of Transforming Growth Factor-β1 and Susceptibility of Pneumoconiosis: A Meta-analysis

    PubMed Central

    Deng, Chang-Wen; Zhang, Xing-Xing; Lin, Jin-Huan; Huang, Li-Fei; Qu, Yu-Lan; Bai, Chong

    2017-01-01

    Background: Transforming growth factor-beta 1 (TGF-β1) and gene variants have been extensively studied in various human diseases. For example, TGF-β1 polymorphisms were associated with fibrosis and pneumoconiosis, but the data remained controversial. The aim of this meta-analysis was to assess the association between TGF-β1 −509 C>T [rs1800469], +869 T>C [rs1800470], and +915 G>C [rs1800471] polymorphisms and pneumoconiosis. Methods: A comprehensive literature search was conducted through searching in PubMed, Embase, the Chinese Biomedical Database, and the Wei Pu (Chinese) Database by the end of April 2016. Eleven publications with 21 studies were included in this meta-analysis, covering a total of 4333 patients with pneumoconiosis and 3478 controls. Study quality was assessed, and heterogeneity and publication bias were measured. All statistical analyses were performed using STATA version 12.0 (StataCorp, College Station, TX, USA) software. Results: The data showed significant associations between TGF-β1 −509 C>T polymorphism and the risk of pneumoconiosis development (T vs. C, odds ratio [OR] = 1.35, 95% confidence interval [CI]: 1.00–1.81, P = 0.046); between TGF-β1 +915 G>C polymorphism and the pneumoconiosis risk (C vs. G, OR = 1.69, 95% CI: 1.19–2.40, P = 0.004; CG vs. GG, OR = 1.79, 95% CI: 1.23–2.60, P = 0.002; CC+CG vs. GG, OR = 1.80, 95% CI: 1.24–2.61, P = 0.002). In addition, the subgroup analysis of ethnicity versus pneumoconiosis types indicated a significant association of silicosis among Asian populations but not that of coal workers’ pneumoconiosis in Caucasian populations. In contrast, no significant association was exhibited between TGF-β1 +869 T>C polymorphism and risk of pneumoconiosis. Conclusion: The polymorphisms of both TGF-β1 −509 C>T and +915 G>C are associated with increased risk of pneumoconiosis. PMID:28139521

  4. Matrix metalloproteinase-2 -1306 C>T gene polymorphism is associated with reduced risk of cancer: a meta-analysis.

    PubMed

    Haque, Shafiul; Akhter, Naseem; Lohani, Mohtashim; Ali, Arif; Mandal, Raju K

    2015-01-01

    Matrix metalloproteinase-2 (MMP2) is an endopeptidase, mainly responsible for degradation of extracellular matrix components, which plays an important role in cancer disease. A single nucleotide polymorphism (SNP) at -1306 disrupts a Sp1-type promoter site. The results from the published studies on the association between MMP2 -1306 C>T polymorphism and cancer risk are contradictory and inconclusive. In the present study, a meta-analysis was therefore performed to evaluate the strength of any association between the MMP2 -1306 C>T polymorphism and risk of cancer. We searched all eligible studies published on association between MMP2 -1306 C>T polymorphism and cancer risk in PubMed (Medline), EMBASE and Google Scholar online web databases until December 2013. Genotype distribution data were collected to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) to examine the strength of the association. A total of 8,590 cancer cases and 9,601 controls were included from twenty nine eligible case control studies. Overall pooled analysis suggested significantly reduced risk associated with heterozygous genotype (CT vs CC: OR=0.758, 95%CI=0.637 to 0.902, p=0.002) and dominant model (TT+CT vs CC: OR=0.816, 95%CI=0.678 to 0.982, p=0.032) genetic models. However, allelic (T vs C: OR=0.882, 95%CI=0.738 to 1.055, p=0.169), homozygous (TT vs CC: OR=1.185, 95%CI=0.825 to 1.700, p=0.358) and recessive (TT vs CC+CT: OR=1.268, 95%CI=0.897 to 1.793, p=0.179) models did not show any risk. No evidence of publication bias was detected during the analysis. The results of present meta-analysis suggest that the MMP2 -1306 C>T polymorphism is significantly associated with reduced risk of cancer. However, further studies with consideration of different populations will be required to evaluate this relationship in more detail.

  5. Association between assisted reproductive technology and the risk of autism spectrum disorders in the offspring: a meta-analysis.

    PubMed

    Liu, Liang; Gao, Junwei; He, Xie; Cai, Yulong; Wang, Lian; Fan, Xiaotang

    2017-04-07

    The association between the use of assisted reproductive technology (ART) and autism spectrum disorder (ASD) risk in offspring has been explored in several studies, but the result is still inconclusive. We assessed the risk of ASD in offspring in relation to ART by conducting a meta-analysis. A literature search in PubMed, Embase, and Web of Knowledge databases through April 30, 2016 was conducted to identify all the relevant records. Risk ratios (RRs) and 95% confidence intervals (95%CIs) were computed to analyze the strength of association by using fixed- or random-effect models based on heterogeneity test in total and subgroup analyses. Analysis of the total 11 records (3 cohort studies and 8 case-control studies) revealed that the use of ART is associated with higher percentage of ASD (RR = 1.35, 95% CI: 1.09-1.68, P = 0.007). In addition, subgroup analyses based on study design, study location and study quality were conducted, and some subgroups also showed a statistically significant association. Our study indicated that the use of ART may associated with higher risk of ASD in the offspring. However, further prospective, large, and high-quality studies are still required.

  6. A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.

    PubMed

    Monda, Keri L; Chen, Gary K; Taylor, Kira C; Palmer, Cameron; Edwards, Todd L; Lange, Leslie A; Ng, Maggie C Y; Adeyemo, Adebowale A; Allison, Matthew A; Bielak, Lawrence F; Chen, Guanjie; Graff, Mariaelisa; Irvin, Marguerite R; Rhie, Suhn K; Li, Guo; Liu, Yongmei; Liu, Youfang; Lu, Yingchang; Nalls, Michael A; Sun, Yan V; Wojczynski, Mary K; Yanek, Lisa R; Aldrich, Melinda C; Ademola, Adeyinka; Amos, Christopher I; Bandera, Elisa V; Bock, Cathryn H; Britton, Angela; Broeckel, Ulrich; Cai, Quiyin; Caporaso, Neil E; Carlson, Chris S; Carpten, John; Casey, Graham; Chen, Wei-Min; Chen, Fang; Chen, Yii-Der I; Chiang, Charleston W K; Coetzee, Gerhard A; Demerath, Ellen; Deming-Halverson, Sandra L; Driver, Ryan W; Dubbert, Patricia; Feitosa, Mary F; Feng, Ye; Freedman, Barry I; Gillanders, Elizabeth M; Gottesman, Omri; Guo, Xiuqing; Haritunians, Talin; Harris, Tamara; Harris, Curtis C; Hennis, Anselm J M; Hernandez, Dena G; McNeill, Lorna H; Howard, Timothy D; Howard, Barbara V; Howard, Virginia J; Johnson, Karen C; Kang, Sun J; Keating, Brendan J; Kolb, Suzanne; Kuller, Lewis H; Kutlar, Abdullah; Langefeld, Carl D; Lettre, Guillaume; Lohman, Kurt; Lotay, Vaneet; Lyon, Helen; Manson, Joann E; Maixner, William; Meng, Yan A; Monroe, Kristine R; Morhason-Bello, Imran; Murphy, Adam B; Mychaleckyj, Josyf C; Nadukuru, Rajiv; Nathanson, Katherine L; Nayak, Uma; N'diaye, Amidou; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M Cristina; Neslund-Dudas, Christine; Neuhouser, Marian; Nyante, Sarah; Ochs-Balcom, Heather; Ogunniyi, Adesola; Ogundiran, Temidayo O; Ojengbede, Oladosu; Olopade, Olufunmilayo I; Palmer, Julie R; Ruiz-Narvaez, Edward A; Palmer, Nicholette D; Press, Michael F; Rampersaud, Evandine; Rasmussen-Torvik, Laura J; Rodriguez-Gil, Jorge L; Salako, Babatunde; Schadt, Eric E; Schwartz, Ann G; Shriner, Daniel A; Siscovick, David; Smith, Shad B; Wassertheil-Smoller, Sylvia; Speliotes, Elizabeth K; Spitz, Margaret R; Sucheston, Lara; Taylor, Herman; Tayo, Bamidele O; Tucker, Margaret A; Van Den Berg, David J; Edwards, Digna R Velez; Wang, Zhaoming; Wiencke, John K; Winkler, Thomas W; Witte, John S; Wrensch, Margaret; Wu, Xifeng; Yang, James J; Levin, Albert M; Young, Taylor R; Zakai, Neil A; Cushman, Mary; Zanetti, Krista A; Zhao, Jing Hua; Zhao, Wei; Zheng, Yonglan; Zhou, Jie; Ziegler, Regina G; Zmuda, Joseph M; Fernandes, Jyotika K; Gilkeson, Gary S; Kamen, Diane L; Hunt, Kelly J; Spruill, Ida J; Ambrosone, Christine B; Ambs, Stefan; Arnett, Donna K; Atwood, Larry; Becker, Diane M; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Borecki, Ingrid B; Bottinger, Erwin P; Bowden, Donald W; Burke, Gregory; Chanock, Stephen J; Cooper, Richard S; Ding, Jingzhong; Duggan, David; Evans, Michele K; Fox, Caroline; Garvey, W Timothy; Bradfield, Jonathan P; Hakonarson, Hakon; Grant, Struan F A; Hsing, Ann; Chu, Lisa; Hu, Jennifer J; Huo, Dezheng; Ingles, Sue A; John, Esther M; Jordan, Joanne M; Kabagambe, Edmond K; Kardia, Sharon L R; Kittles, Rick A; Goodman, Phyllis J; Klein, Eric A; Kolonel, Laurence N; Le Marchand, Loic; Liu, Simin; McKnight, Barbara; Millikan, Robert C; Mosley, Thomas H; Padhukasahasram, Badri; Williams, L Keoki; Patel, Sanjay R; Peters, Ulrike; Pettaway, Curtis A; Peyser, Patricia A; Psaty, Bruce M; Redline, Susan; Rotimi, Charles N; Rybicki, Benjamin A; Sale, Michèle M; Schreiner, Pamela J; Signorello, Lisa B; Singleton, Andrew B; Stanford, Janet L; Strom, Sara S; Thun, Michael J; Vitolins, Mara; Zheng, Wei; Moore, Jason H; Williams, Scott M; Ketkar, Shamika; Zhu, Xiaofeng; Zonderman, Alan B; Kooperberg, Charles; Papanicolaou, George J; Henderson, Brian E; Reiner, Alex P; Hirschhorn, Joel N; Loos, Ruth J F; North, Kari E; Haiman, Christopher A

    2013-06-01

    Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.

  7. Association between arterial stiffness, cerebral small vessel disease and cognitive impairment: a systematic review and meta-analysis

    PubMed Central

    van Sloten, Thomas T; Protogerou, Athanase D; Henry, Ronald MA; Schram, Miranda T; Launer, Lenore J; Stehouwer, Coen DA

    2017-01-01

    Arterial stiffness may be a cause of cerebral small vessel disease and cognitive impairment. We therefore performed a systematic review and meta-analysis of studies on the association between stiffness, cerebral small vessel disease and cognitive impairment. For the associations between stiffness (i.e. carotid-femoral pulse wave velocity (cfPWV), brachial-ankle PWV (baPWV), carotid stiffness and pulse pressure) on the one hand and cerebral small vessel disease and cognitive impairment on the other, we identified 23 (n=15,666/22 cross-sectional/3 longitudinal) and 41 studies (n=57,671/30 cross-sectional/15 longitudinal), respectively. Pooled analyses of cross-sectional studies showed that greater stiffness was associated with markers of cerebral small vessel disease with odds ratios, per +1 SD, of 1.29 to 1.32 (P<.001). Studies on cognitive impairment could not be pooled due to large heterogeneity. Some (but not all) studies showed an association between greater stiffness and cognitive impairment, and the strength of this association was relatively weak. The present study supports the hypothesis that greater arterial stiffness is a contributor to microvascular brain disease. PMID:25827412

  8. Associations between parental psychological control and relational aggression in children and adolescents: a multilevel and sequential meta-analysis.

    PubMed

    Kuppens, Sofie; Laurent, Laura; Heyvaert, Mieke; Onghena, Patrick

    2013-09-01

    Youth aggression has been associated with negative parenting practices, but previous research about this association has mainly focused on physical and verbal aggression. Because more subtle forms of aggression are considered at least as harmful as their physical and verbal counterparts, there is a growing scientific interest in parenting practices that are linked with relational aggression. Guided by social learning theory, a link between youth relational aggression and parental psychological control has been postulated, but the empirical evidence is inconsistent. The present meta-analysis provides a multilevel and sequential quantitative synthesis of 165 dependent effect sizes (23 studies) encompassing 8,958 youths. Across studies, a positive, albeit weak, association between parental psychological control and relational aggression was found. The sequential analysis demonstrated that sufficient cumulative knowledge was attained to yield convincing evidence on this overall association. Moderator analyses revealed that developmental period and assessment method were associated with differences in research findings. Overall, however, results suggest that clarifying the precise role of psychological control in the development and maintenance of relational aggression requires more targeted primary research, which in turn would allow additional and more complex synthesis efforts with potentially more nuanced conclusions.

  9. Associations between joint effusion in the knee and gene expression levels in the circulation: a meta-analysis

    PubMed Central

    Peters, Marjolein J.; Ramos, Yolande F.M.; den Hollander, Wouter; Schiphof, Dieuwke; Hofman, Albert; Uitterlinden, André G.; Oei, Edwin H.G.; Slagboom, P. Eline; Kloppenburg, Margreet; Bloem, Johan L.; Bierma-Zeinstra, Sita M.A.; Meulenbelt, Ingrid; van Meurs, Joyce B.J.

    2016-01-01

    Objective: To identify molecular biomarkers for early knee osteoarthritis (OA), we examined whether joint effusion in the knee associated with different gene expression levels in the circulation. Materials and Methods: Joint effusion grades measured with magnetic resonance (MR) imaging and gene expression levels in blood were determined in women of the Rotterdam Study (N=135) and GARP (N=98). Associations were examined using linear regression analyses, adjusted for age, fasting status, RNA quality, technical batch effects, blood cell counts, and BMI. To investigate enriched pathways and protein-protein interactions, we used the DAVID and STRING webtools. Results: In a meta-analysis, we identified 257 probes mapping to 189 unique genes in blood that were nominally significantly associated with joint effusion grades in the knee. Several compelling genes were identified such as C1orf38 and NFATC1. Significantly enriched biological pathways were: response to stress, gene expression, negative regulation of intracellular signal transduction, and antigen processing and presentation of exogenous pathways. Conclusion: Meta-analyses and subsequent enriched biological pathways resulted in interesting candidate genes associated with joint effusion that require further characterization. Associations were not transcriptome-wide significant most likely due to limited power. Additional studies are required to replicate our findings in more samples, which will greatly help in understanding the pathophysiology of OA and its relation to inflammation, and may result in biomarkers urgently needed to diagnose OA at an early stage. PMID:27134727

  10. A Meta-Analysis Identifies New Loci Associated with Body Mass index in Individuals of African Ancestry

    PubMed Central

    Monda, Keri L.; Chen, Gary K.; Taylor, Kira C.; Palmer, Cameron; Edwards, Todd L.; Lange, Leslie A.; Ng, Maggie C.Y.; Adeyemo, Adebowale A.; Allison, Matthew A.; Bielak, Lawrence F.; Chen, Guanji; Graff, Mariaelisa; Irvin, Marguerite R.; Rhie, Suhn K.; Li, Guo; Liu, Yongmei; Liu, Youfang; Lu, Yingchang; Nalls, Michael A.; Sun, Yan V.; Wojczynski, Mary K.; Yanek, Lisa R.; Aldrich, Melinda C.; Ademola, Adeyinka; Amos, Christopher I.; Bandera, Elisa V.; Bock, Cathryn H.; Britton, Angela; Broeckel, Ulrich; Cai, Quiyin; Caporaso, Neil E.; Carlson, Chris; Carpten, John; Casey, Graham; Chen, Wei-Min; Chen, Fang; Chen, Yii-Der I.; Chiang, Charleston W.K.; Coetzee, Gerhard A.; Demerath, Ellen; Deming-Halverson, Sandra L.; Driver, Ryan W.; Dubbert, Patricia; Feitosa, Mary F.; Freedman, Barry I.; Gillanders, Elizabeth M.; Gottesman, Omri; Guo, Xiuqing; Haritunians, Talin; Harris, Tamara; Harris, Curtis C.; Hennis, Anselm JM; Hernandez, Dena G.; McNeill, Lorna H.; Howard, Timothy D.; Howard, Barbara V.; Howard, Virginia J.; Johnson, Karen C.; Kang, Sun J.; Keating, Brendan J.; Kolb, Suzanne; Kuller, Lewis H.; Kutlar, Abdullah; Langefeld, Carl D.; Lettre, Guillaume; Lohman, Kurt; Lotay, Vaneet; Lyon, Helen; Manson, JoAnn E.; Maixner, William; Meng, Yan A.; Monroe, Kristine R.; Morhason-Bello, Imran; Murphy, Adam B.; Mychaleckyj, Josyf C.; Nadukuru, Rajiv; Nathanson, Katherine L.; Nayak, Uma; N’Diaye, Amidou; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina; Neslund-Dudas, Christine; Neuhouser, Marian; Nyante, Sarah; Ochs-Balcom, Heather; Ogunniyi, Adesola; Ogundiran, Temidayo O.; Ojengbede, Oladosu; Olopade, Olufunmilayo I.; Palmer, Julie R.; Ruiz-Narvaez, Edward A.; Palmer, Nicholette D.; Press, Michael F.; Rampersaud, Evandine; Rasmussen-Torvik, Laura J.; Rodriguez-Gil, Jorge L.; Salako, Babatunde; Schadt, Eric E.; Schwartz, Ann G.; Shriner, Daniel A.; Siscovick, David; Smith, Shad B.; Wassertheil-Smoller, Sylvia; Speliotes, Elizabeth K.; Spitz, Margaret R.; Sucheston, Lara; Taylor, Herman; Tayo, Bamidele O.; Tucker, Margaret A.; Van Den Berg, David J.; Velez Edwards, Digna R.; Wang, Zhaoming; Wiencke, John K.; Winkler, Thomas W.; Witte, John S.; Wrensch, Margaret; Wu, Xifeng; Yang, James J.; Levin, Albert M.; Young, Taylor R.; Zakai, Neil A.; Cushman, Mary; Zanetti, Krista A.; Zhao, Jing Hua; Zhao, Wei; Zheng, Yonglan; Zhou, Jie; Ziegler, Regina G.; Zmuda, Joseph M.; Fernandes, Jyotika K.; Gilkeson, Gary S.; Kamen, Diane L.; Hunt, Kelly J.; Spruill, Ida J.; Ambrosone, Christine B.; Ambs, Stefan; Arnett, Donna K.; Atwood, Larry; Becker, Diane M.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Borecki, Ingrid B.; Bottinger, Erwin P.; Bowden, Donald W.; Burke, Gregory; Chanock, Stephen J.; Cooper, Richard S.; Ding, Jingzhong; Duggan, David; Evans, Michele K.; Fox, Caroline; Garvey, W. Timothy; Bradfield, Jonathan P.; Hakonarson, Hakon; Grant, Struan F.A.; Hsing, Ann; Chu, Lisa; Hu, Jennifer J.; Huo, Dezheng; Ingles, Sue A.; John, Esther M.; Jordan, Joanne M.; Kabagambe, Edmond K.; Kardia, Sharon L.R.; Kittles, Rick A.; Goodman, Phyllis J.; Klein, Eric A.; Kolonel, Laurence N.; Le Marchand, Loic; Liu, Simin; McKnight, Barbara; Millikan, Robert C.; Mosley, Thomas H.; Padhukasahasram, Badri; Williams, L. Keoki; Patel, Sanjay R.; Peters, Ulrike; Pettaway, Curtis A.; Peyser, Patricia A.; Psaty, Bruce M.; Redline, Susan; Rotimi, Charles N.; Rybicki, Benjamin A.; Sale, Michèle M.; Schreiner, Pamela J.; Signorello, Lisa B.; Singleton, Andrew B.; Stanford, Janet L.; Strom, Sara S.; Thun, Michael J.; Vitolins, Mara; Zheng, Wei; Moore, Jason H.; Williams, Scott M.; Zhu, Xiaofeng; Zonderman, Alan B.; Kooperberg, Charles; Papanicolaou, George; Henderson, Brian E.; Reiner, Alex P.; Hirschhorn, Joel N.; Loos, Ruth JF; North, Kari E.; Haiman, Christopher A.

    2013-01-01

    Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry, and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one novel locus at 5q33 (GALNT10, rs7708584, p=3.4×10−11) and another at 7p15 when combined with data from the Giant consortium (MIR148A/NFE2L3, rs10261878, p=1.2×10−10). We also found suggestive evidence of an association at a third locus at 6q16 in the African ancestry sample (KLHL32, rs974417, p=6.9×10−8). Thirty-two of the 36 previously established BMI variants displayed directionally consistent effect estimates in our GWAS (binomial p=9.7×10−7), of which five reached genome-wide significance. These findings provide strong support for shared BMI loci across populations as well as for the utility of studying ancestrally diverse populations. PMID:23583978

  11. Association between assisted reproductive technology and the risk of autism spectrum disorders in the offspring: a meta-analysis

    PubMed Central

    liu, Liang; Gao, Junwei; He, Xie; Cai, Yulong; Wang, Lian; Fan, Xiaotang

    2017-01-01

    The association between the use of assisted reproductive technology (ART) and autism spectrum disorder (ASD) risk in offspring has been explored in several studies, but the result is still inconclusive. We assessed the risk of ASD in offspring in relation to ART by conducting a meta-analysis. A literature search in PubMed, Embase, and Web of Knowledge databases through April 30, 2016 was conducted to identify all the relevant records. Risk ratios (RRs) and 95% confidence intervals (95%CIs) were computed to analyze the strength of association by using fixed- or random-effect models based on heterogeneity test in total and subgroup analyses. Analysis of the total 11 records (3 cohort studies and 8 case-control studies) revealed that the use of ART is associated with higher percentage of ASD (RR = 1.35, 95% CI: 1.09–1.68, P = 0.007). In addition, subgroup analyses based on study design, study location and study quality were conducted, and some subgroups also showed a statistically significant association. Our study indicated that the use of ART may associated with higher risk of ASD in the offspring. However, further prospective, large, and high-quality studies are still required. PMID:28387368

  12. Associations of Different Adipose Tissue Depots with Insulin Resistance: A Systematic Review and Meta-analysis of Observational Studies.

    PubMed

    Zhang, Mingzhi; Hu, Tian; Zhang, Shaoyan; Zhou, Li

    2015-12-21

    Fat distribution is strongly associated with insulin resistance, a risk factor for type 2 diabetes and cardiovascular diseases. However, associations of different adipose tissue depots or/and obesity indices with insulin resistance have not been systematically evaluated. In this study we examined associations of different adipose tissue depots/obesity indices with insulin resistance, as measured by homeostatic model assessment of insulin resistance (HOMA-IR) in observational studies. A total of 40 studies with 56 populations and 29 adipose tissue depots/obesity indices were included in the meta-analysis. There were strong correlation between HOMA-IR and visceral fat mass (r = 0.570, 95% confidence interval(CI): 0.424~0.687), total fat mass (r = 0.492, 95%CI: 0.407~0.570), body mass index (r = 0.482, 95%CI: 0.445~0.518) and waist circumference (r = 0.466, 95%CI: 0.432~0.500), except lower extremity fat (r = 0.088, 95%CI: -0.116~0.285). Sample size, diabetic status, gender, mean of body mass index, and race contributed to heterogeneity of these associations. This study showed a positive correlation between insulin resistance and most adipose tissue depots/obesity indices, and the strongest association is for visceral fat mass.

  13. The association between vitamin D and COPD risk, severity, and exacerbation: an updated systematic review and meta-analysis

    PubMed Central

    Zhu, Min; Wang, Ting; Wang, Chengdi; Ji, Yulin

    2016-01-01

    Background In recent years, the pleiotropic roles of vitamin D have been highlighted in various diseases. However, the association between serum vitamin D and COPD is not well studied. This updated systematic review and meta-analysis aimed to assess the relationship between vitamin D and the risk, severity, and exacerbation of COPD. Methods A systematic literature search was conducted in PubMed, Medline, EMBASE, Chinese National Knowledge Infrastructure, Wanfang, and Weipu databases. The pooled risk estimates were standardized mean difference (SMD) with 95% confidence interval (CI) for vitamin D levels and odds ratio (OR) with 95% CI for vitamin D deficiency. Meta-regression and subgroup analyses were performed on latitude, body mass index, and assay method. Results A total of 21 studies, including 4,818 COPD patients and 7,175 controls, were included. Meta-analysis showed that lower serum vitamin D levels were found in COPD patients than in controls (SMD: −0.69, 95% CI: −1.00, −0.38, P<0.001), especially in severe COPD (SMD: −0.87, 95% CI: −1.51, −0.22, P=0.001) and COPD exacerbation (SMD: −0.43, 95% CI: −0.70, −0.15, P=0.002). Vitamin D deficiency was associated with increased risk of COPD (OR: 1.77, 95% CI: 1.18, 2.64, P=0.006) and with COPD severity (OR: 2.83, 95% CI: 2.00, 4.00, P<0.001) but not with COPD exacerbation (OR: 1.17, 95% CI: 0.86, 1.59, P=0.326). Assay methods had significant influence on the heterogeneity of vitamin D deficiency and COPD risk. Conclusion Serum vitamin D levels were inversely associated with COPD risk, severity, and exacerbation. Vitamin D deficiency is associated with increased risk of COPD and severe COPD but not with COPD exacerbation. It is worth considering assay methods in the heterogeneity sources analysis of association between vitamin D deficiency and COPD. PMID:27799758

  14. RASSF1A promoter methylation is associated with increased risk of thyroid cancer: a meta-analysis

    PubMed Central

    Shou, Feiyan; Xu, Feng; Li, Gang; Zhao, Zhenhua; Mao, Ying; Yang, Fangfang; Wang, Hongming; Guo, Hangyuan

    2017-01-01

    Objective Previous studies have reported that Ras-associated domain family 1A (RASSF1A), the most commonly silenced tumor suppressor via promoter methylation, played vital roles in the development of carcinogenesis. The purpose of this meta-analysis was to determine whether RASSF1A promoter methylation increased the risk of thyroid cancer. Methods PubMed, Embase, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure databases were searched to obtain eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations, using Stata 12.0 software. The methodological quality of included studies was evaluated using Newcastle–Ottawa scale table. Egger’s test and Begg’s test were applied to detect publication biases. TSA 0.9 software was used to calculate the required information size and whether the result was conclusive. Results A total of 10 articles with 12 studies that included 422 thyroid cancer patients, identifying the association of RASSF1A promoter methylation with thyroid cancer risk, were collected in this meta-analysis. Overall, RASSF1A promoter methylation significantly increased the risk of thyroid cancer (total, OR=8.27, CI=4.38–15.62, P<0.05; Caucasian, OR=9.25, CI=3.97–21.56, P<0.05; Asian, OR=7.01, CI=2.68–18.38, P<0.05). In the subgroup analysis based on sample type, a significant association between thyroid cancer group and control group was found (normal tissue, OR=9.55, CI=4.21–21.67, P<0.05; adjacent tissue, OR=6.80, CI=2.49–18.56, P<0.05). The frequency of RASSF1A promoter methylation in follicular thyroid carcinoma was higher than in control group (OR=11.88, CI=5.80–24.32, P<0.05). In addition, the results indicated that the RASSF1A promoter methylation was correlated with papillary thyroid carcinoma in Caucasians and Asians (total, OR=8.07, CI=3.54–18.41, P<0.05; Caucasian, OR=11.35, CI=2.39–53.98, P<0.05; Asian, OR=6.67, CI=2.53–17

  15. Associations between Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms and Non-Alcoholic Fatty Liver Disease (NAFLD) Risk: A Meta-Analysis

    PubMed Central

    Sun, Man-Yi; Zhang, Li; Shi, Song-Li; Lin, Jing-Na

    2016-01-01

    Background C677T and A1298C are the most common allelic variants of Methylenetetrahydrofolate Reductase (MTHFR) gene. The association between MTHFR polymorphisms and the occurrence of non-alcoholic fatty liver disease (NAFLD) remains controversial. This study was thus performed to examine whether MTHFR mutations are associated with the susceptibility to NAFLD. Methods A first meta-analysis on the association between the MTHFR polymorphisms and NAFLD risks was carried out via Review Manager 5.0 and Stata/SE 12.0 software. The on-line databases, such as PubMed, EMBASE, CENTRAL, WOS, Scopus and EBSCOhost (updated to April 1st, 2016), were searched for eligible case-control studies. The odd radio (OR), 95% confidence interval (CI) and P value were calculated through Mantel-Haenszel statistics under random- or fixed-effect model. Results Eight articles (785 cases and 1188 controls) contributed data to the current meta-analysis. For C677T, increased NAFLD risks were observed in case group under homozygote model (T/T vs C/C, OR = 1.49, 95% CI = 1.03~2.15, P = 0.04) and recessive model (T/T vs C/C+C/T, OR = 1.42, 95% CI = 1.07~1.88, P = 0.02), but not the other genetics models, compared with control group. For A1298C, significantly increased NAFLD risks were detected in allele model (C vs A, OR = 1.53, 95% CI = 1.13~2.07, P = 0.006), homozygote model (C/C vs A/A, OR = 2.81, 95% CI = 1.63~4.85, P = 0.0002), dominant model (A/C+C/C vs A/A, OR = 1.60, 95% CI = 1.06~2.41, P = 0.03) and recessive model (C/C vs A/A+A/C, OR = 2.08, 95% CI = 1.45~3.00, P<0.0001), but not heterozygote model. Conclusion T/T genotype of MTHFR C677T polymorphism and C/C genotype of MTHFR A1298C are more likely to be associated with the susceptibility to NAFLD. PMID:27128842

  16. Risk Factors Associated with Renal Involvement in Childhood Henoch-Schönlein Purpura: A Meta-Analysis

    PubMed Central

    Chan, Han; Tang, Yan-Ling; Lv, Xiao-Hang; Zhang, Gao-Fu; Wang, Mo; Yang, Hai-Ping; Li, Qiu

    2016-01-01

    Background and objective Henoch-Schönlein purpura (HSP) is an important cause of chronic kidney disease in children. This meta-analysis identified risk factors associated with renal involvement in childhood HSP. Methods PubMed, Embase, and Web of Science were searched. The quality of all eligible studies was assessed using the Newcastle-Ottawa scale criteria. An analysis of possible risk factors was conducted to report the odds ratio (OR) and weighted mean difference (WMD). Results Thirteen studies (2398 children) revealed 20 possible and 13 significant risk factors associated with renal involvement in HSP, with the following meta-analysis estimates of OR and WMD, with 95% confidence intervals: older age (0.90, 0.61–1.19); age > 10 y (3.13, 1.39–7.07); male gender (1.36, 1.07–1.74); abdominal pain (1.94,1.24–3.04); gastrointestinal bleeding (1.86, 1.30–2.65); severe bowel angina (3.38, 1.17–9.80); persistent purpura (4.02, 1.22–13.25); relapse (4.70, 2.42–9.14); WBC > 15 × 109/L (2.42, 1.39–4.22); platelets > 500 × 109/L (2.98, 1.22–7.25); elevated antistreptolysin O (ASO) (2.17, 1.29–3.64); and decreased complement component 3 (C3) (3.13, 1.62–6.05). Factors not significantly associated with renal involvement were: blood pressure; orchitis; elevated C-reactive protein; elevated erythrocyte sedimentation rate (ESR); and elevated serum IgA/IgE or IgG. Arthritis/arthralgia may be a risk factor according to the criteria of the American College of Rheumatology (1.41, 1.01–1.96). Conclusion The following are associated with renal involvement in pediatric HSP: male gender; > 10 y old; severe gastrointestinal symptoms (abdominal pain, gastrointestinal bleeding, and severe bowel angina); arthritis/arthralgia; persistent purpura or relapse; WBC > 15 × 109/L; platelets > 500 × 109/L; elevated ASO; and low C3. Relevant clinical interventions for these risk factors may exert positive effects on the prevention of kidney disease during the early

  17. Association between subjective social status and cardiovascular disease and cardiovascular risk factors: a systematic review and meta-analysis

    PubMed Central

    Tang, Karen L; Rashid, Ruksana; Godley, Jenny; Ghali, William A

    2016-01-01

    Objective To determine the association between subjective social status (SSS), or the individual's perception of his or her position in the social hierarchy, and the odds of coronary artery disease (CAD), hypertension, diabetes, obesity and dyslipidaemia. Study Design Systematic review and meta-analysis. Methods We searched PubMed, MEDLINE, EMBASE, CINAHL, PsycINFO, SocINDEX, Web of Science and reference lists of all included studies up to October 2014, with a verification search in July 2015. Inclusion criteria were original studies in adults that reported odds, risk or hazard ratios of at least one outcome of interest (CAD, hypertension, diabetes, obesity or dyslipidaemia), comparing ‘lower’ versus ‘higher’ SSS groups, where SSS is measured on a self-anchoring ladder. ORs were pooled using a random-effects model. Results 10 studies were included in the systematic review; 9 of these were included in the meta-analysis. In analyses unadjusted for objective socioeconomic status (SES) measures such as income, education or occupation, the pooled OR comparing the bottom versus the top of the SSS ladder was 1.82 (95% CI 1.10 to 2.99) for CAD, 1.88 (95% CI 1.27 to 2.79) for hypertension, 1.90 (95% CI 1.25 to 2.87) for diabetes, 3.68 (95% CI 2.03 to 6.64) for dyslipidaemia and 1.57 (95% CI 0.95 to 2.59) for obesity. These associations were attenuated when adjusting for objective SES measures, with the only statistically significant association remaining for dyslipidaemia (OR 2.10, 95% CI 1.09 to 4.06), though all ORs remained greater than 1. Conclusions Lower SSS is associated with significantly increased odds of CAD, hypertension, diabetes and dyslipidaemia, with a trend towards increased odds of obesity. These trends are consistently present, though the effects attenuated when adjusting for SES, suggesting that perception of one's own status on a social hierarchy has health effects above and beyond one's actual income, occupation and education. PMID:26993622

  18. MtDNA meta-analysis reveals both phenotype specificity and allele heterogeneity: a model for differential association

    PubMed Central

    Marom, Shani; Friger, Michael; Mishmar, Dan

    2017-01-01

    Human mtDNA genetic variants have traditionally been considered markers for ancient population migrations. However, during the past three decades, these variants have been associated with altered susceptibility to various phenotypes, thus supporting their importance for human health. Nevertheless, mtDNA disease association has frequently been supported only in certain populations, due either to population stratification or differential epistatic compensations among populations. To partially overcome these obstacles, we performed meta-analysis of the multiple mtDNA association studies conducted until 2016, encompassing 53,975 patients and 63,323 controls. Our findings support the association of mtDNA haplogroups and recurrent variants with specific phenotypes such as Parkinson’s disease, type 2 diabetes, longevity, and breast cancer. Strikingly, our assessment of mtDNA variants’ involvement with multiple phenotypes revealed significant impact for Caucasian haplogroups H, J, and K. Therefore, ancient mtDNA variants could be divided into those that affect specific phenotypes, versus others with a general impact on phenotype combinations. We suggest that the mtDNA could serve as a model for phenotype specificity versus allele heterogeneity. PMID:28230165

  19. Associations between maternal and paternal parenting behaviors, anxiety and its precursors in early childhood: A meta-analysis.

    PubMed

    Möller, Eline L; Nikolić, Milica; Majdandžić, Mirjana; Bögels, Susan M

    2016-04-01

    In this meta-analysis we investigated differential associations between maternal and paternal parenting behaviors (overcontrol, overprotection, overinvolvement, autonomy granting, challenging parenting) and anxiety and its precursors (fearful temperament, behavioral inhibition, shyness) in children (0-5years). Two meta-analyses were conducted, one for mothers (k=28, N=5,728), and one for fathers (k=12, N=1,019). In general, associations between parenting and child anxiety were small. Associations between child anxiety and overcontrol, overprotection, and overinvolvement did not differ for mothers and fathers. Maternal autonomy granting was not significantly related to child anxiety, and no studies examined fathers' autonomy granting. A significant difference was found for challenging parenting; mothers' challenging parenting was not significantly related to child anxiety, whereas fathers' challenging parenting was related to less child anxiety. Post-hoc meta-analyses revealed that mothers' and fathers' parenting was more strongly related to children's anxiety symptoms than to child anxiety precursors. Moreover, the association between parenting and child anxiety symptoms was stronger for fathers than for mothers. In conclusion, although parenting plays only a small role in early childhood anxiety, fathers' parenting is at least as important as mothers'. Paternal challenging behavior even seems more important than maternal challenging behavior. Research is needed to determine whether challenging fathering can prevent child anxiety development.

  20. Probiotics are effective at preventing Clostridium difficile-associated diarrhea: a systematic review and meta-analysis

    PubMed Central

    Lau, Christine SM; Chamberlain, Ronald S

    2016-01-01

    Introduction Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea. CDI has increased in incidence and severity over the past decade, and is a growing worldwide health problem associated with substantial health care costs and significant morbidity and mortality. This meta-analysis examines the impact of probiotics on the incidence of Clostridium difficile-associated diarrhea (CDAD) among children and adults, in both hospital and outpatient settings. Methods A comprehensive literature search of all published randomized control trials (RCTs) assessing the use of probiotics in the prevention of CDAD in patients receiving antibiotic therapy was conducted, and the incidence of CDAD was analyzed. Results Twenty-six RCTs involving 7,957 patients were analyzed. Probiotic use significantly reduced the risk of developing CDAD by 60.5% (relative risk [RR] =0.395; 95% confidence interval [CI], 0.294–0.531; P<0.001). Probiotics proved beneficial in both adults and children (59.5% and 65.9% reduction), especially among hospitalized patients. Lactobacillus, Saccharomyces, and a mixture of probiotics were all beneficial in reducing the risk of developing CDAD (63.7%, 58.5%, and 58.2% reduction). Conclusion Probiotic supplementation is associated with a significant reduction in the risk of developing CDAD in patients receiving antibiotics. Additional studies are required to determine the optimal dose and strain of probiotic. PMID:26955289

  1. Association between dietary fiber and lower risk of all-cause mortality: a meta-analysis of cohort studies.

    PubMed

    Yang, Yang; Zhao, Long-Gang; Wu, Qi-Jun; Ma, Xiao; Xiang, Yong-Bing

    2015-01-15

    Although in vitro and in vivo experiments have suggested that dietary fiber might have beneficial effects on health, results on the association between fiber intake and all-cause mortality in epidemiologic studies have been inconsistent. Therefore, we conducted a meta-analysis of prospective cohort studies to quantitatively assess this association. Pertinent studies were identified by searching articles in PubMed and Web of Knowledge through May 2014 and reviewing the reference lists of the retrieved articles. Study-specific risk estimates were combined using random-effects models. Seventeen prospective studies (1997-2014) that had a total of 67,260 deaths and 982,411 cohort members were included. When comparing persons with dietary fiber intakes in the top tertile with persons whose intakes were in the bottom tertile, we found a statistically significant inverse association between fiber intake and all-cause mortality, with an overall relative risk of 0.84 (95% confidence interval: 0.80, 0.87; I(2) = 41.2%). There was a 10% reduction in risk for per each 10-g/day increase in fiber intake (relative risk = 0.90; 95% confidence interval: 0.86, 0.94; I(2) = 77.2%). The combined estimate was robust across subgroup and sensitivity analyses. No publication bias was detected. A higher dietary fiber intake was associated with a reduced risk of death. These findings suggest that fiber intake may offer a potential public health benefit in reducing all-cause mortality.

  2. Association between Proton Pump Inhibitor Therapy and Clostridium difficile Infection: A Contemporary Systematic Review and Meta-Analysis

    PubMed Central

    Tleyjeh, Imad M.; Alasmari, Faisal A.; Garbati, Musa A.; AlGhamdi, Mushabab; Khan, Abdur Rahman; Tannir, Mohamad Al; Erwin, Patricia J.; Ibrahim, Talal; AlLehibi, Abed; Baddour, Larry M.; Sutton, Alex J.

    2012-01-01

    Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship. PMID:23236397

  3. Increased Eating Frequency Is Associated with Lower Obesity Risk, But Higher Energy Intake in Adults: A Meta-Analysis

    PubMed Central

    Wang, Yue-Qiao; Zhang, Yun-Quan; Zhang, Fei; Zhang, Yi-Wen; Li, Rui; Chen, Guo-Xun

    2016-01-01

    Body weight is regulated by energy intake which occurs several times a day in humans. In this meta-analysis, we evaluated whether eating frequency (EF) is associated with obesity risk and energy intake in adults without any dietary restriction. Experimental and observational studies published before July 2015 were selected through English-language literature searches in several databases. These studies reported the association between EF and obesity risk (odd ratios, ORs) in adults who were not in dietary restriction. R software was used to perform statistical analyses. Ten cross-sectional studies, consisting of 65,742 participants, were included in this analysis. ORs were considered as effect size for the analysis about the effect of EF on obesity risk. Results showed that the increase of EF was associated with 0.83 time lower odds of obesity (i.e., OR = 0.83, 95% confidence intervals (CI) 0.70–0.99, p = 0.040). Analysis about the effect of EF on differences in participants’ energy intake revealed that increased EF was associated with higher energy intake (β = 125.36, 95% CI 21.76–228.97, p = 0.017). We conclude that increased EF may lead to lower obesity risk but higher energy intake. Clinical trials are warranted to confirm these results and to assess the clinical practice applicability. PMID:27322302

  4. Association between the BDNF G196A and C270T polymorphisms and Parkinson's disease: a meta-analysis.

    PubMed

    Dai, Limeng; Wang, Dongmei; Meng, Hui; Zhang, Kun; Fu, Liyuan; Wu, Yuanyuan; Bai, Yun

    2013-10-01

    Epidemiological studies have evaluated the associations between brain-derived neurotrophic factor (BDNF) polymorphisms and Parkinson's disease (PD) risk. However, the results remain inconsistent. Therefore, we conducted a meta-analysis of published case-control studies to better understand these results. Systematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles were performed. The pooled odds ratio (OR) with 95% confidence interval (CI) were calculated. All the statistical tests were performed using Review Manager 5.1 and Stata 11.0. A total of 13 case-control studies were included, involving two polymorphisms (G196A and C270T) of BDNF gene and covering 3333 PD cases and 3418 controls. No significant associations were found on the overall analysis both G196A and C270T polymorphisms. In the subgroup analysis by ethnicity (Caucasian, Asian and Mixed population), there were still no detectable associations. In conclusion, there is no enough evidence for associations between BDNF polymorphisms (G196A and C270T) and PD risk at present. Larger sample-size and multiethnicity studies with homogeneous PD patients and well-matched controls are needed in the future study.

  5. Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis

    PubMed Central

    Zhu, Ling-Yan; Li, Yu; Yu, Jiao; Wang, Jiao; Zeng, Xiang-Xia; Hu, Kai-Xiang; Liu, Jian-Ying

    2017-01-01

    Studies have suggested that metformin can potentially decrease the incidence of cancer and improve survival outcomes. However, the association between metformin use and the incidence and survival of endometrial cancer (EC) remains controversial. So, a meta-analysis was performed. An electronic search was conducted using PubMed, EMBASE, and Web of Science. The outcome measures were relative risks (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs) comparing the EC incidence and survival in patients treated with and without metformin. Eleven studies involving 766,926 participants were included in this study. In the pooled analysis of five studies which evaluated the association of metformin use with the incidence of EC, we found that metformin use was associated with a 13% reduction in EC risk among patients with diabetes (RR = 0.87, 95% CI: 0.80–0.95; p = 0.006). In the pooled analysis of six retrospective cohort studies evaluating the effect of metformin on the survival of EC patients, we found that, relative to nonuse, metformin use significantly improved the survival of EC patients (HR = 0.63, 95% CI: 0.45–0.87; p = 0.006). This study showed that metformin use was significantly associated with a decreased incidence of EC in diabetes and a favorable survival outcome of EC patients.

  6. Association of vitamin D receptor Fok I polymorphism with the risk of prostate cancer: a meta-analysis

    PubMed Central

    Kang, Shaosan; Zhao, Yansheng; Liu, Jian; Wang, Lei; Zhao, Geng; Chen, Xi; Yao, Anliang; Zhang, Liguo; Zhang, Xiaojun; Li, Xiaoqiang

    2016-01-01

    Several previous studies have been reported to examine the association between Vitamin D receptor (VDR) gene Fok I polymorphism and susceptibility to prostate cancer (PCa), however the results remain inconclusive. To provide a relatively comprehensive account of the association, we searched PubMed, Embase, CNKI, and Wanfang for eligible studies and carry out this meta-analysis. A total of 27 case-control studies with 10,486 cases and 10,400 controls were included. In the overall analysis, Fok I polymorphism was not significantly associated with the susceptibility to PCa. Subgroup analyses showed that significantly association was existed in Caucasian population, the subgroup of population-based controls and the stratified group with advanced tumor.These results indicate that the VDR Fok I polymorphism might be capable of causing PCa susceptibility and could be a promising target to forecast the PCa risk for clinical practice. However further well-designed epidemiologic studies are needed to confirm this conclusion. PMID:27788484

  7. Meta-analysis of the association of the SLC6A3 3'-UTR VNTR with cognition.

    PubMed

    Ettinger, Ulrich; Merten, Natascha; Kambeitz, Joseph

    2016-01-01

    The gene coding for the dopamine transporter (DAT), SLC6A3, contains a 40-base pair variable number of tandem repeats (VNTR) polymorphism (rs28363170) in its 3' untranslated region. This VNTR has been associated with attention deficit hyperactivity disorder (ADHD) and has been investigated in relation to cognition and brain function. Here, we report the results of a comprehensive meta-analysis with meta-regression examining the association of the VNTR with different domains of cognition in healthy adults. We extracted data from 28 independent studies and carried out meta-analyses for associations with working memory (k=10 samples, N=1193 subjects), inhibition (k=8 samples, N=829 subjects), executive functions including inhibition (k=10 samples, N=984 subjects), attention (k=6 samples, N=742 subjects) and declarative long-term memory (k=5 samples, N=251 subjects). None of the investigated dimensions showed significant associations with the VNTR (all p>0.26). Meta-regression including year of publication, gender, age, ethnicity and percentage of 10R-homozygotes similarly did not attain significance. We conclude that there is no evidence that rs28363170 may be a significant predictor of cognitive function in healthy adults.

  8. Six Novel Loci Associated with Circulating VEGF Levels Identified by a Meta-analysis of Genome-Wide Association Studies

    PubMed Central

    Song, Ci; Nutile, Teresa; Vernon Smith, Albert; Concas, Maria Pina; Traglia, Michela; Barbieri, Caterina; Ndiaye, Ndeye Coumba; Stathopoulou, Maria G.; Lagou, Vasiliki; Maestrale, Giovanni Battista; Sala, Cinzia; Debette, Stephanie; Kovacs, Peter; Lind, Lars; Lamont, John; Fitzgerald, Peter; Tönjes, Anke; Gudnason, Vilmundur; Toniolo, Daniela; Pirastu, Mario; Bellenguez, Celine; Vasan, Ramachandran S.; Ingelsson, Erik; Leutenegger, Anne-Louise; Johnson, Andrew D.; DeStefano, Anita L.; Visvikis-Siest, Sophie; Seshadri, Sudha; Ciullo, Marina

    2016-01-01

    Vascular endothelial growth factor (VEGF) is an angiogenic and neurotrophic factor, secreted by endothelial cells, known to impact various physiological and disease processes from cancer to cardiovascular disease and to be pharmacologically modifiable. We sought to identify novel loci associated with circulating VEGF levels through a genome-wide association meta-analysis combining data from European-ancestry individuals and using a dense variant map from 1000 genomes imputation panel. Six discovery cohorts including 13,312 samples were analyzed, followed by in-silico and de-novo replication studies including an additional 2,800 individuals. A total of 10 genome-wide significant variants were identified at 7 loci. Four were novel loci (5q14.3, 10q21.3, 16q24.2 and 18q22.3) and the leading variants at these loci were rs114694170 (MEF2C, P = 6.79x10-13), rs74506613 (JMJD1C, P = 1.17x10-19), rs4782371 (ZFPM1, P = 1.59x10-9) and rs2639990 (ZADH2, P = 1.72x10-8), respectively. We also identified two new independent variants (rs34528081, VEGFA, P = 1.52x10-18; rs7043199, VLDLR-AS1, P = 5.12x10-14) at the 3 previously identified loci and strengthened the evidence for the four previously identified SNPs (rs6921438, LOC100132354, P = 7.39x10-1467; rs1740073, C6orf223, P = 2.34x10-17; rs6993770, ZFPM2, P = 2.44x10-60; rs2375981, KCNV2, P = 1.48x10-100). These variants collectively explained up to 52% of the VEGF phenotypic variance. We explored biological links between genes in the associated loci using Ingenuity Pathway Analysis that emphasized their roles in embryonic development and function. Gene set enrichment analysis identified the ERK5 pathway as enriched in genes containing VEGF associated variants. eQTL analysis showed, in three of the identified regions, variants acting as both cis and trans eQTLs for multiple genes. Most of these genes, as well as some of those in the associated loci, were involved in platelet biogenesis and functionality, suggesting the

  9. Risk factors associated with medial tibial stress syndrome in runners: a systematic review and meta-analysis

    PubMed Central

    Newman, Phil; Witchalls, Jeremy; Waddington, Gordon; Adams, Roger

    2013-01-01

    Background Medial tibial stress syndrome (MTSS) affects 5%–35% of runners. Research over the last 40 years investigating a range of interventions has not established any clearly effective management for MTSS that is better than prolonged rest. At the present time, understanding of the risk factors and potential causative factors for MTSS is inconclusive. The purpose of this review is to evaluate studies that have investigated various risk factors and their association with the development of MTSS in runners. Methods Medical research databases were searched for relevant literature, using the terms “MTSS AND prevention OR risk OR prediction OR incidence”. Results A systematic review of the literature identified ten papers suitable for inclusion in a meta-analysis. Measures with sufficient data for meta-analysis included dichotomous and continuous variables of body mass index (BMI), ankle dorsiflexion range of motion, navicular drop, orthotic use, foot type, previous history of MTSS, female gender, hip range of motion, and years of running experience. The following factors were found to have a statistically significant association with MTSS: increased hip external rotation in males (standard mean difference [SMD] 0.67, 95% confidence interval [CI] 0.29–1.04, P<0.001); prior use of orthotics (risk ratio [RR] 2.31, 95% CI 1.56–3.43, P<0.001); fewer years of running experience (SMD −0.74, 95% CI −1.26 to −0.23, P=0.005); female gender (RR 1.71, 95% CI 1.15–2.54, P=0.008); previous history of MTSS (RR 3.74, 95% CI 1.17–11.91, P=0.03); increased body mass index (SMD 0.24, 95% CI 0.08–0.41, P=0.003); navicular drop (SMD 0.26, 95% CI 0.02–0.50, P=0.03); and navicular drop >10 mm (RR 1.99, 95% CI 1.00–3.96, P=0.05). Conclusion Female gender, previous history of MTSS, fewer years of running experience, orthotic use, increased body mass index, increased navicular drop, and increased external rotation hip range of motion in males are all significantly

  10. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium.

    PubMed

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

    2016-03-01

    Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

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

    PubMed

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

    2015-10-01

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

  12. Association of MTDH immunohistochemical expression with metastasis and prognosis in female reproduction malignancies: a systematic review and meta-analysis

    PubMed Central

    Hou, Yongbin; Yu, Lihua; Mi, Yonghua; Zhang, Jiwang; Wang, Ke; Hu, Liyi

    2016-01-01

    Various literatures have demonstrated that overexpression of Metadherin (MTDH) is correlated with tumor metastasis and it can predict poor survival outcomes in female reproduction malignancies. In order to enhance the statistical power and reach a recognized conclusion, we conducted a systematic review and meta-analysis to thoroughly investigate the association of MTDH expression with tumor metastasis and survival outcomes following PRISMA guidelines. Odds ratios (ORs) and hazard ratios (HRs) were used to demonstrate the impact of MTDH on tumor metastasis and prognosis respectively. Data were pooled with appropriate effects model on STATA12.0. Our results indicated that high MTDH expression is significantly correlated with higher mortality for breast, ovarian and cervical cancer. High immunohistochemical expression of MTDH is remarkably associated with shorter disease-free survival (DFS) in breast cancer but not in ovarian cancer. The pooled results suggested that high level of MTDH significantly predicted distant metastasis and lymph node metastasis in breast cancer. Strong associations were observed between MTDH expression and lymph node metastasis in ovarian and cervical cancer. In conclusion, MTDH might be a novel biomarker which can effectively reflect metastasis status and prognosis of breast cancer. However, its application in clinical practice needs more prospective studies with large samples. PMID:27917902

  13. Lower Level of Bacteroides in the Gut Microbiota Is Associated with Inflammatory Bowel Disease: A Meta-Analysis

    PubMed Central

    Zhou, Yingting

    2016-01-01

    Background and Aims. Multiple studies have reported associations between inflammatory bowel disease (IBD) and the flora disequilibrium of Bacteroides. We performed a meta-analysis of the available data to provide a more precise estimate of the association between Bacteroides level in the gut and IBD. Methods. We searched PubMed/MEDLINE, EMBASE, Cochrane Library, Wiley Library, BIOSIS previews, Web of Science, CNKI, and ScienceDirect databases for published literature on IBD and gut microbiota from 1990 to 2016. Quality of all eligible studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). We compared the level of Bacteroides in IBD patients with that in a control group without IBD, different types of IBD patients, and IBD patients with active phase and in remission. Results. We identified 63 articles, 9 of which contained sufficient data for evaluation. The mean level of Bacteroides was significantly lower in Crohn's disease (CD) and ulcerative colitis (UC) patients in active phase than in normal controls. The level of Bacteroides in remission CD and UC patients was much lower than patients in the control group. Bacteroides level was even lower in patients with CD and UC in active phase than in remission. Conclusions. This analysis suggests that lower levels of Bacteroides are associated with IBD, especially in active phase. PMID:27999802

  14. Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci

    PubMed Central

    He, Meian; Xu, Min; Zhang, Ben; Liang, Jun; Chen, Peng; Lee, Jong-Young; Johnson, Todd A.; Li, Huaixing; Yang, Xiaobo; Dai, Juncheng; Liang, Liming; Gui, Lixuan; Qi, Qibin; Huang, Jinyan; Li, Yanping; Adair, Linda S.; Aung, Tin; Cai, Qiuyin; Cheng, Ching-Yu; Cho, Myeong-Chan; Cho, Yoon Shin; Chu, Minjie; Cui, Bin; Gao, Yu-Tang; Go, Min Jin; Gu, Dongfeng; Gu, Weiqiong; Guo, Huan; Hao, Yongchen; Hong, Jie; Hu, Zhibin; Hu, Yanling; Huang, Jianfeng; Hwang, Joo-Yeon; Ikram, Mohammad Kamran; Jin, Guangfu; Kang, Dae-Hee; Khor, Chiea Chuen; Kim, Bong-Jo; Kim, Hung Tae; Kubo, Michiaki; Lee, Jeannette; Lee, Juyoung; Lee, Nanette R.; Li, Ruoying; Li, Jun; Liu, JianJun; Longe, Jirong; Lu, Wei; Lu, Xiangfeng; Miao, Xiaoping; Okada, Yukinori; Ong, Rick Twee-Hee; Qiu, Gaokun; Seielstad, Mark; Sim, Xueling; Song, Huaidong; Takeuchi, Fumihiko; Tanaka, Toshihiro; Taylor, Phil R.; Wang, Laiyuan; Wang, Weiqing; Wang, Yiqin; Wu, Chen; Wu, Ying; Xiang, Yong-Bing; Yamamoto, Ken; Yang, Handong; Liao, Ming; Yokota, Mitsuhiro; Young, Terri; Zhang, Xiaomin; Kato, Norihiro; Wang, Qing K.; Zheng, Wei; Hu, Frank B.; Lin, Dongxin; Shen, Hongbing; Teo, Yik Ying; Mo, Zengnan; Wong, Tien Yin; Lin, Xu; Mohlke, Karen L.; Ning, Guang; Tsunoda, Tatsuhiko; Han, Bok-Ghee; Shu, Xiao-Ou; Tai, E. Shyong; Wu, Tangchun; Qi, Lu

    2015-01-01

    Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity. Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci. A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns. We carried out a GWA meta-analysis in 93 926 individuals from East Asia. We identified 98 loci, including 17 novel and 81 previously reported loci, associated with height at P < 5 × 10−8, together explaining 8.89% of phenotypic variance. Among the newly identified variants, 10 are commonly distributed (minor allele frequency, MAF > 5%) in Europeans, with comparable frequencies with in Asians, and 7 single-nucleotide polymorphisms are with low frequency (MAF < 5%) in Europeans. In addition, our data suggest that novel biological pathway such as the protein tyrosine phosphatase family is involved in regulation of height. The findings from this study considerably expand our knowledge of the genetic architecture of human height in Asians. PMID:25429064

  15. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.

    PubMed

    Nalls, Mike A; Pankratz, Nathan; Lill, Christina M; Do, Chuong B; Hernandez, Dena G; Saad, Mohamad; DeStefano, Anita L; Kara, Eleanna; Bras, Jose; Sharma, Manu; Schulte, Claudia; Keller, Margaux F; Arepalli, Sampath; Letson, Christopher; Edsall, Connor; Stefansson, Hreinn; Liu, Xinmin; Pliner, Hannah; Lee, Joseph H; Cheng, Rong; Ikram, M Arfan; Ioannidis, John P A; Hadjigeorgiou, Georgios M; Bis, Joshua C; Martinez, Maria; Perlmutter, Joel S; Goate, Alison; Marder, Karen; Fiske, Brian; Sutherland, Margaret; Xiromerisiou, Georgia; Myers, Richard H; Clark, Lorraine N; Stefansson, Kari; Hardy, John A; Heutink, Peter; Chen, Honglei; Wood, Nicholas W; Houlden, Henry; Payami, Haydeh; Brice, Alexis; Scott, William K; Gasser, Thomas; Bertram, Lars; Eriksson, Nicholas; Foroud, Tatiana; Singleton, Andrew B

    2014-09-01

    We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation.

  16. No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis.

    PubMed

    Loley, Christina; Alver, Maris; Assimes, Themistocles L; Bjonnes, Andrew; Goel, Anuj; Gustafsson, Stefan; Hernesniemi, Jussi; Hopewell, Jemma C; Kanoni, Stavroula; Kleber, Marcus E; Lau, King Wai; Lu, Yingchang; Lyytikäinen, Leo-Pekka; Nelson, Christopher P; Nikpay, Majid; Qu, Liming; Salfati, Elias; Scholz, Markus; Tukiainen, Taru; Willenborg, Christina; Won, Hong-Hee; Zeng, Lingyao; Zhang, Weihua; Anand, Sonia S; Beutner, Frank; Bottinger, Erwin P; Clarke, Robert; Dedoussis, George; Do, Ron; Esko, Tõnu; Eskola, Markku; Farrall, Martin; Gauguier, Dominique; Giedraitis, Vilmantas; Granger, Christopher B; Hall, Alistair S; Hamsten, Anders; Hazen, Stanley L; Huang, Jie; Kähönen, Mika; Kyriakou, Theodosios; Laaksonen, Reijo; Lind, Lars; Lindgren, Cecilia; Magnusson, Patrik K E; Marouli, Eirini; Mihailov, Evelin; Morris, Andrew P; Nikus, Kjell; Pedersen, Nancy; Rallidis, Loukianos; Salomaa, Veikko; Shah, Svati H; Stewart, Alexandre F R; Thompson, John R; Zalloua, Pierre A; Chambers, John C; Collins, Rory; Ingelsson, Erik; Iribarren, Carlos; Karhunen, Pekka J; Kooner, Jaspal S; Lehtimäki, Terho; Loos, Ruth J F; März, Winfried; McPherson, Ruth; Metspalu, Andres; Reilly, Muredach P; Ripatti, Samuli; Sanghera, Dharambir K; Thiery, Joachim; Watkins, Hugh; Deloukas, Panos; Kathiresan, Sekar; Samani, Nilesh J; Schunkert, Heribert; Erdmann, Jeanette; König, Inke R

    2016-10-12

    In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD.

  17. Association of C722T polymorphism in XRCC3 gene with larynx cancer: a meta-analysis.

    PubMed

    Li, Dong; You, Hui-Hua; Jia, Yuan-Jing; Guo, Jian-Dong; Du, Huan-Le

    2014-06-01

    Several case-control studies indicated that XRCC3 genetic polymorphism (C722T) was associated with larynx cancer. The present study aimed to further evaluate the relation between the XRCC3 gene C722T polymorphism and larynx cancer. We selected five case-control studies related to XRCC3 gene C722T polymorphism and larynx cancer by searching PubMed, EMBase, Chinese CNKI, and Wanfang database. RevMan 5.0 software was used to perform the analysis. We directly utilized Q test and I (2) test to test the heterogeneity between each study. We utilized the fixed effects model to merge the odds ratio (OR) and 95 % confidence interval. There were 1,507 larynx cancer patients and 3,623 cancer-free control subjects included in the present study. By meta-analysis, we did not find any association of XRCC3 gene C722T polymorphism with larynx cancer [OR=1.54, 95 % CI (0.77-3.08); P=0.22]. The present study indicated that XRCC3 gene C722T polymorphism was not associated with larynx cancer.

  18. Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis

    PubMed Central

    Corvol, Harriet; Blackman, Scott M.; Boëlle, Pierre-Yves; Gallins, Paul J.; Pace, Rhonda G.; Stonebraker, Jaclyn R.; Accurso, Frank J.; Clement, Annick; Collaco, Joseph M.; Dang, Hong; Dang, Anthony T.; Franca, Arianna; Gong, Jiafen; Guillot, Loic; Keenan, Katherine; Li, Weili; Lin, Fan; Patrone, Michael V.; Raraigh, Karen S.; Sun, Lei; Zhou, Yi-Hui; O'Neal, Wanda K.; Sontag, Marci K.; Levy, Hara; Durie, Peter R.; Rommens, Johanna M.; Drumm, Mitchell L.; Wright, Fred A.; Strug, Lisa J.; Cutting, Garry R.; Knowles, Michael R.

    2015-01-01

    The identification of small molecules that target specific CFTR variants has ushered in a new era of treatment for cystic fibrosis (CF), yet optimal, individualized treatment of CF will require identification and targeting of disease modifiers. Here we use genome-wide association analysis to identify genetic modifiers of CF lung disease, the primary cause of mortality. Meta-analysis of 6,365 CF patients identifies five loci that display significant association with variation in lung disease. Regions on chr3q29 (MUC4/MUC20; P=3.3 × 10−11), chr5p15.3 (SLC9A3; P=6.8 × 10−12), chr6p21.3 (HLA Class II; P=1.2 × 10−8) and chrXq22-q23 (AGTR2/SLC6A14; P=1.8 × 10−9) contain genes of high biological relevance to CF pathophysiology. The fifth locus, on chr11p12-p13 (EHF/APIP; P=1.9 × 10−10), was previously shown to be associated with lung disease. These results provide new insights into potential targets for modulating lung disease severity in CF. PMID:26417704

  19. The association between phosphatase and tensin homolog hypermethylation and patients with breast cancer, a meta-analysis and literature review

    PubMed Central

    Lu, Yi-Min; Cheng, Feng; Teng, Li-Song

    2016-01-01

    The Phosphatase and tensin homolog (PTEN) protein is a negative regulator of the Akt pathway, leading to suppression of apoptois and increased cell survival. Its role as a tumor-suppressor gene has been adequately substantiated, and PTEN hypermethylation has been demonstrated in familial and sporadic cancers. However, the association and clinical significance between PTEN hypermethylation and breast cancer remains unclear. In this study, we systematically reviewed studies of PTEN hypermethylation and breast cancer and quantify the association between PTEN hypermethylation and breast cancer using meta-analysis methods. The pooled OR, 22.30, 95% confidential intervals, CI = 1.98–251.51, P = 0.01, which demonstrates that loss of PTEN expression by hypermethylation plays a critical role in the early tumorigenesis of ductal carcinoma in situ (DCIS). In addition, PTEN hypermethylation also is detected in invasive ductal carcinomas (IDCs) and is significantly higher than in normal controls, OR = 23.32, 95% CI = 10.43–52.13, P < 0.00001. Further analysis did not show significant correlation between PTEN hypermethylation and the progression of breast cancer, estrogen receptor (ER), progesterone receptor (PgR), as well as HER2 status. These results indicate the PTEN hypermethylation is significantly associated with both DCIS and IDCs. The detection of PTEN hypermethylation could be an early tumorigenesis marker for breast cancer patients. PMID:27620353

  20. No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis

    PubMed Central

    Loley, Christina; Alver, Maris; Assimes, Themistocles L.; Bjonnes, Andrew; Goel, Anuj; Gustafsson, Stefan; Hernesniemi, Jussi; Hopewell, Jemma C.; Kanoni, Stavroula; Kleber, Marcus E.; Lau, King Wai; Lu, Yingchang; Lyytikäinen, Leo-Pekka; Nelson, Christopher P.; Nikpay, Majid; Qu, Liming; Salfati, Elias; Scholz, Markus; Tukiainen, Taru; Willenborg, Christina; Won, Hong-Hee; Zeng, Lingyao; Zhang, Weihua; Anand, Sonia S.; Beutner, Frank; Bottinger, Erwin P.; Clarke, Robert; Dedoussis, George; Do, Ron; Esko, Tõnu; Eskola, Markku; Farrall, Martin; Gauguier, Dominique; Giedraitis, Vilmantas; Granger, Christopher B.; Hall, Alistair S.; Hamsten, Anders; Hazen, Stanley L.; Huang, Jie; Kähönen, Mika; Kyriakou, Theodosios; Laaksonen, Reijo; Lind, Lars; Lindgren, Cecilia; Magnusson, Patrik K. E.; Marouli, Eirini; Mihailov, Evelin; Morris, Andrew P.; Nikus, Kjell; Pedersen, Nancy; Rallidis, Loukianos; Salomaa, Veikko; Shah, Svati H.; Stewart, Alexandre F. R.; Thompson, John R.; Zalloua, Pierre A.; Chambers, John C.; Collins, Rory; Ingelsson, Erik; Iribarren, Carlos; Karhunen, Pekka J.; Kooner, Jaspal S.; Lehtimäki, Terho; Loos, Ruth J. F.; März, Winfried; McPherson, Ruth; Metspalu, Andres; Reilly, Muredach P.; Ripatti, Samuli; Sanghera, Dharambir K.; Thiery, Joachim; Watkins, Hugh; Deloukas, Panos; Kathiresan, Sekar; Samani, Nilesh J.; Schunkert, Heribert; Erdmann, Jeanette; König, Inke R.

    2016-01-01

    In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD. PMID:27731410

  1. Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis

    PubMed Central

    Trindade, E; Menon, D; Topfer, L A; Coloma, C

    1998-01-01

    BACKGROUND: The use of antidepressant medications and the resulting costs have increased dramatically in recent years, partly because of the introduction of selective serotonin reuptake inhibitors (SSRIs). An assessment of the clinical and economic aspects of SSRIs compared with the older tricyclic antidepressants (TCAs) was initiated to generate information for purchasers of these drugs as well as clinicians. One component of this study was an examination of the adverse effects associated with the use of these drugs. METHODS: Searches of bibliographic databases (for January 1980 through May 1996) and manual scanning of both peer-reviewed publications and other documents were used to identify double-blind, randomized controlled trials involving at least one SSRI and one TCA. For the study of adverse effects, only trials that had at least 20 patients in each trial arm and that reported rates of adverse effects in both arms were retained. In total 84 trials reporting on 18 adverse effects were available. Meta-analyses were undertaken to calculate pooled differences in rates of adverse effects. The question of whether the method of eliciting information from patients about adverse effects made a difference in the findings was also examined. Finally, differences in drop-out rates due to adverse effects were calculated. RESULTS: The crude rates of occurrence of adverse effects ranged from 4% (palpitations) to 26% (nausea) for SSRIs and from 4% (diarrhea) to 27% (dry mouth) for TCAs. The differences in the rates of adverse effects between the 2 types of drugs ranged from 14% more with SSRIs (for nausea) to 11% more with TCAs (for constipation). The results did not depend on the method of eliciting information from patients. There were no statistically significant differences between drug classes in terms of drop-outs due to adverse effects. INTERPRETATION: SSRIs and TCAs are both associated with adverse effects, although the key effects differ between the drug classes

  2. Genetic variants of homocysteine/folate metabolism pathway and risk of inflammatory bowel disease: a synopsis and meta-analysis of genetic association studies.

    PubMed

    Zintzaras, Elias

    2010-02-01

    A synopsis and meta-analysis of studies that investigated the association between genetic variants involved in the homocysteine/folate metabolism pathway and risk of inflammatory bowel disease (IBD) were conducted. Four variants (MTHFR C6TTT, MTHFR A1298C, MTR A2756G and MTRR A66G) showed significant associations in individual studies. In meta-analyses, only the variant MTR A2756G indicated an association with the risk of IBD for the allele contrast and the dominant model (odds ratio (OR) 1.48 (1.12-1.97) and OR 1.55 (1.12-2.15), respectively). The effect sizes for Crohn's disease and ulcerative colitis were similar to IBD. Cumulative meta-analysis for C677T indicated a downward trend of association as information accumulates.

  3. Lactobacillus probiotics in the prevention of diarrhea associated with Clostridium difficile: a systematic review and Bayesian hierarchical meta-analysis

    PubMed Central

    Sinclair, Alison; Xie, Xuanqian; Saab, Lama; Dendukuri, Nandini

    2016-01-01

    Background: Recent meta-analyses of the efficacy of probiotics for preventing diarrhea associated with Clostridium difficile have concluded there is a large effect favouring probiotics. We reexamined this evidence, which contradicts the results of a more recent large randomized controlled trial that found no benefit of Lactobacillus probiotics for preventing C. difficile-associated diarrhea. Methods: We performed a systematic review of the efficacy of treatment with Lactobacillus probiotics for preventing nosocomial C. difficile-associated diarrhea in adults and carried out a meta-analysis using a Bayesian hierarchical model. We used credibility analysis and meta-regression to characterize the heterogeneity between studies. Results: Ten studies met our inclusion criteria. The pooled risk ratio was highly statistically significant, at 0.25 (95% credible interval 0.08-0.47). However, the 95% prediction interval for the risk ratio in a future study, 0.02-1.34, was wider than the credible interval, owing to heterogeneity between studies. Furthermore, a credibility analysis showed that the strength of the evidence was weaker than the observed number of cases of C. difficile-associated diarrhea across studies would suggest. Meta-regression suggested that the beneficial effect of probiotics was more likely to be reported in studies with an increased risk of C. difficile-associated diarrhea in the control group, although this association was not statistically significant. Interpretation: Accounting for between-study heterogeneity showed that there is considerable uncertainty regarding the apparently large efficacy estimate associated with Lactobacillus probiotic treatment in preventing C. difficile-associated diarrhea. Most studies to date have been carried out in populations with a low risk of C. difficile-associated diarrhea, such that the evidence is inconclusive and inadequate to support a policy concerning routine use of probiotics in to prevent this condition. PMID

  4. A meta-analysis of the association of estimated GFR, albuminuria, diabetes mellitus, and hypertension with AKI

    PubMed Central

    James, Matthew T.; Grams, Morgan E.; Woodward, Mark; Elley, C. Raina; Green, Jamie A.; Wheeler, David C.; de Jong, Paul; Gansevoort, Ron T.; Levey, Andrew S.; Warnock, David G.; Sarnak, Mark J.

    2015-01-01

    Background Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain. Study Design Meta-analysis of cohort studies. Setting & Population 8 general population (1,285,045 participants) and 5 CKD (79,519 participants) cohorts. Selection Criteria for Studies Cohorts participating in the CKD Prognosis Consortium. Predictors Diabetes and hypertension status, eGFR by the CKD Epidemiology Collaboration 2009 creatinine equation, urine ACR, and interactions. Outcome Hospitalization with AKI, using Cox proportional hazards models to estimate hazard ratios (HR) of AKI and random effects meta-analysis to pool results. Results Over a mean follow-up period of 4 years, there were 16,480 episodes of AKI in the general population and 2,087 episodes in the CKD cohorts. Low eGFR and high ACR were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR 80 mL/min/1.73m2 in non-diabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared to non-diabetic patients. The risk gradient for AKI with lower eGFR was greater in those without diabetes than with diabetes, but similar with higher ACR in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFR greater than 60 ml/min/1.73m2 than those without hypertension. However, the risk gradients for AKI with both lower eGFR and higher ACR were greater for those without than with hypertension. Limitations AKI identified by diagnostic code. Conclusions Lower eGFR and higher ACR are associated with higher risks of AKI among individuals with or without either diabetes or hypertension. PMID:25975964

  5. Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a systematic review and meta-analysis

    PubMed Central

    Dillon, David G; Gurdasani, Deepti; Riha, Johanna; Ekoru, Kenneth; Asiki, Gershim; Mayanja, Billy N; Levitt, Naomi S; Crowther, Nigel J; Nyirenda, Moffat; Njelekela, Marina; Ramaiya, Kaushik; Nyan, Ousman; Adewole, Olanisun O; Anastos, Kathryn; Azzoni, Livio; Boom, W Henry; Compostella, Caterina; Dave, Joel A; Dawood, Halima; Erikstrup, Christian; Fourie, Carla M; Friis, Henrik; Kruger, Annamarie; Idoko, John A; Longenecker, Chris T; Mbondi, Suzanne; Mukaya, Japheth E; Mutimura, Eugene; Ndhlovu, Chiratidzo E; Praygod, George; Pefura Yone, Eric W; Pujades-Rodriguez, Mar; Range, Nyagosya; Sani, Mahmoud U; Schutte, Aletta E; Sliwa, Karen; Tien, Phyllis C; Vorster, Este H; Walsh, Corinna; Zinyama, Rutendo; Mashili, Fredirick; Sobngwi, Eugene; Adebamowo, Clement; Kamali, Anatoli; Seeley, Janet; Young, Elizabeth H; Smeeth, Liam; Motala, Ayesha A; Kaleebu, Pontiano; Sandhu, Manjinder S

    2013-01-01

    Background Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations. Methods We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants. Results Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, −0.59; 95% CI, −0.86 to −0.31), BMI (SMD, −0.32; 95% CI, −0.45 to −0.18), SBP (SMD, −0.40; 95% CI, −0.55 to −0.25) and DBP (SMD, −0.34; 95% CI, −0.51 to −0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, −0.34; 95% CI, −0.62 to −0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits. Conclusions Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the

  6. The Association Between Serum Levels of Selenium, Copper, and Magnesium with Thyroid Cancer: a Meta-analysis.

    PubMed

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

    2015-10-01

    There are conflicting reports on the correlation between serum levels of selenium (Se), copper (Cu), and magnesium (Mg) with thyroid cancer. The purpose of the present study is to clarify the association between Se, Cu, and Mg levels with thyroid cancer using a meta-analysis approach. We searched articles indexed in PubMed published as of January 2015 that met our predefined criteria. Eight eligible articles involving 1291 subjects were identified. Overall, pooled analysis indicated that subjects with thyroid cancer had lower serum levels of Se and Mg, but higher levels of Cu than the healthy controls [Se: standardized mean difference (SMD) = -0.485, 95% confidence interval (95%CI) = (-0.878, -0.092), p = 0.016; Cu: SMD = 2.372, 95%CI = (0.945, 3.799), p = 0.001; Mg: SMD = -0.795, 95%CI = (-1.092, -0.498), p < 0.001]. Further subgroup analysis found lower serum levels of Se in thyroid cancer in Norway [SMD = -0.410, 95%CI = (-0.758, -0.062), p = 0.021] and Austria [SMD = -0.549, 95%CI = (-0.743, -0.355), p < 0.001], but not in Poland (SMD = -0.417, 95%CI = (-1.724, 0.891), p = 0.532]. Further subgroup analysis also found that patients with thyroid cancer had higher serum levels of Cu in China [SMD = 1.571, 95%CI = (1.121, 2.020), p < 0.001] and Turkey [SMD = 0.977, 95%CI = (0.521, 1.432), p < 0.001], but not in Poland [SMD = 3.471, 95%CI = (-0.056, 6.997], p = 0.054]. In conclusion, this meta-analysis supports a significant association between serum levels of Se, Cu, and Mg with thyroid cancer. However, the subgroup analysis found that there was significant effect modification of Se, Cu levels by ethnic, like China and Poland. Thus, this finding needs further confirmation by a trans-regional multicenter study to obtain better understanding of causal relationship between Se, Cu, and Mg with thyroid cancer of different human races or regions.

  7. Genome-wide association study meta-analysis reveals transethnic replication of mean arterial and pulse pressure loci.

    PubMed

    Kelly, Tanika N; Takeuchi, Fumihiko; Tabara, Yasuharu; Edwards, Todd L; Kim, Young Jin; Chen, Peng; Li, Huaixing; Wu, Ying; Yang, Chi-Fan; Zhang, Yonghong; Gu, Dongfeng; Katsuya, Tomohiro; Ohkubo, Takayoshi; Gao, Yu-Tang; Go, Min Jin; Teo, Yik Ying; Lu, Ling; Lee, Nanette R; Chang, Li-Ching; Peng, Hao; Zhao, Qi; Nakashima, Eitaro; Kita, Yoshikuni; Shu, Xiao-Ou; Kim, Nam Hee; Tai, E Shyong; Wang, Yiqin; Adair, Linda S; Chen, Chien-Hsiun; Zhang, Shihiu; Li, Changwei; Nabika, Toru; Umemura, Satoshi; Cai, Qiuyin; Cho, Yoon Shin; Wong, Tien Yin; Zhu, Jingwen; Wu, Jer-Yuarn; Gao, Xin; Hixson, James E; Cai, Hui; Lee, Juyoung; Cheng, Ching-Yu; Rao, Dabeeru C; Xiang, Yong-Bing; Cho, Myeong-Chan; Han, Bok-Ghee; Wang, Aili; Tsai, Fuu-Jen; Mohlke, Karen; Lin, Xu; Ikram, Mohammad Kamran; Lee, Jong-Young; Zheng, Wei; Tetsuro, Miki; Kato, Norihiro; He, Jiang

    2013-11-01

    We conducted a genome-wide association study meta-analysis of mean arterial pressure and pulse pressure among 26,600 East Asian participants (stage 1) followed by replication study of up to 28,783 participants (stage 2). For novel loci, statistical significance was determined by a P<5.0×10(-8) in joint analysis of stage 1 and stage 2 data. For loci reported by the previous mean arterial and pulse pressure genome-wide association study meta-analysis in Europeans, evidence of transethnic replication was determined by consistency in effect direction and a Bonferroni-corrected P<1.4×10(-3). No novel loci were identified by the current study. Five independent mean arterial pressure variants demonstrated robust evidence for transethnic replication including rs17249754 at ATP2B1 (P=7.5×10(-15)), rs2681492 at ATP2B1 (P=3.4×10(-7)), rs11191593 at NT5C2 (1.1×10(-6)), rs3824755 at CYP17A1 (P=1.2×10(-6)), and rs13149993 at FGF5 (P=2.4×10(-4)). Two additional variants showed suggestive evidence of transethnic replication (consistency in effect direction and P<0.05), including rs319690 at MAP4 (P=0.014) and rs1173771 at NPR3 (P=0.018). For pulse pressure, robust evidence of replication was identified for 2 independent variants, including rs17249754 at ATP2B1 (P=1.2×10(-5)) and rs11191593 at NT5C2 (P=1.1×10(-3)), with suggestive evidence of replication among an additional 2 variants including rs3824755 at CYP17A1 (P=6.1×10(-3)) and rs2681492 at ATP2B1 (P=9.0×10(-3)). Replicated variants demonstrated consistency in effect sizes between East Asian and European samples, with effect size differences ranging from 0.03 to 0.24 mm Hg for mean arterial pressure and from 0.03 to 0.21 mm Hg for pulse pressure. In conclusion, we present the first evidence of transethnic replication of several mean arterial and pulse pressure loci in an East Asian population.

  8. Vaccines are not associated with autism: an evidence-based meta-analysis of case-control and cohort studies.

    PubMed

    Taylor, Luke E; Swerdfeger, Amy L; Eslick, Guy D

    2014-06-17

    There has been enormous debate regarding the possibility of a link between childhood vaccinations and the subsequent development of autism. This has in recent times become a major public health issue with vaccine preventable diseases increasing in the community due to the fear of a 'link' between vaccinations and autism. We performed a meta-analysis to summarise available evidence from case-control and cohort studies on this topic (MEDLINE, PubMed, EMBASE, Google Scholar up to April, 2014). Eligible studies assessed the relationship between vaccine administration and the subsequent development of autism or autism spectrum disorders (ASD). Two reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus with another author. Five cohort studies involving 1,256,407 children, and five case-control studies involving 9,920 children were included in this analysis. The cohort data revealed no relationship between vaccination and autism (OR: 0.99; 95% CI: 0.92 to 1.06) or ASD (OR: 0.91; 95% CI: 0.68 to 1.20), nor was there a relationship between autism and MMR (OR: 0.84; 95% CI: 0.70 to 1.01), or thimerosal (OR: 1.00; 95% CI: 0.77 to 1.31), or mercury (Hg) (OR: 1.00; 95% CI: 0.93 to 1.07). Similarly the case-control data found no evidence for increased risk of developing autism or ASD following MMR, Hg, or thimerosal exposure when grouped by condition (OR: 0.90, 95% CI: 0.83 to 0.98; p=0.02) or grouped by exposure type (OR: 0.85, 95% CI: 0.76 to 0.95; p=0.01). Findings of this meta-analysis suggest that vaccinations are not associated with the development of autism or autism spectrum disorder. Furthermore, the components of the vaccines (thimerosal or mercury) or multiple vaccines (MMR) are not associated with the development of autism or autism spectrum disorder.

  9. Association between 8q24 (rs13281615 and rs6983267) polymorphism and breast cancer susceptibility: a meta-analysis involving 117,355 subjects.

    PubMed

    Zhang, Yafei; Zeng, Xianling; Lu, Hongwei; Ji, Hong; Zhao, Enfa; Li, Yiming

    2016-10-18

    Published data on the association between 8q24 polymorphism and breast cancer (BC) risk are inconclusive. Thus, we conducted a meta-analysis to evaluate the relationship between 8q24 (rs13281615 and rs6983267) polymorphism and BC risk. We searched PubMed, EMBASE, Web of science and the Cochrane Library up to August 13, 2015 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. Twenty-six studies published from 2008 to 2014, with a total of 52,683 cases and 64,672 controls, were included in this meta-analysis. The pooled results showed that there was significant association between 8q24 rs13281615 polymorphism and BC risk in any genetic model. In the subgroup analysis by ethnicity, the effects remained in Asians and Caucasians. However, no genetic models reached statistical association in Africans. There was no association in any genetic model in rs6983267. This meta-analysis suggests that 8q24 rs13281615 polymorphism is a risk factor for susceptibility to BC in Asians, Caucasians and in overall population, While, there was no association in Africans. The rs6983267 polymorphism has no association with BC risk in any genetic model. Further large scale multicenter epidemiological studies are warranted to confirm this finding.

  10. Replication and Characterization of Association between ABO SNPs and Red Blood Cell Traits by Meta-Analysis in Europeans

    PubMed Central

    McLachlan, Stela; Giambartolomei, Claudia; Charoen, Pimphen; Wong, Andrew; Finan, Chris; Engmann, Jorgen; Shah, Tina; Hersch, Micha; Cavadino, Alana; Jefferis, Barbara J.; Dale, Caroline E.; Hypponen, Elina; Morris, Richard W.; Casas, Juan P.; Kumari, Meena; Ben-Shlomo, Yoav; Gaunt, Tom R.; Drenos, Fotios; Langenberg, Claudia; Kuh, Diana; Kivimaki, Mika; Rueedi, Rico; Waeber, Gerard; Hingorani, Aroon D.; Price, Jacqueline F.

    2016-01-01

    Red blood cell (RBC) traits are routinely measured in clinical practice as important markers of health. Deviations from the physiological ranges are usually a sign of disease, although variation between healthy individuals also occurs, at least partly due to genetic factors. Recent large scale genetic studies identified loci associated with one or more of these traits; further characterization of known loci and identification of new loci is necessary to better understand their role in health and disease and to identify potential molecular mechanisms. We performed meta-analysis of Metabochip association results for six RBC traits—hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV) and red blood cell count (RCC)—in 11 093 Europeans from seven studies of the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium. We identified 394 non-overlapping SNPs in five loci at genome-wide significance: 6p22.1-6p21.33 (with HFE among others), 6q23.2 (with HBS1L among others), 6q23.3 (contains no genes), 9q34.3 (only ABO gene) and 22q13.1 (with TMPRSS6 among others), replicating previous findings of association with RBC traits at these loci and extending them by imputation to 1000 Genomes. We further characterized associations between ABO SNPs and three traits: hemoglobin, hematocrit and red blood cell count, replicating them in an independent cohort. Conditional analyses indicated the independent association of each of these traits with ABO SNPs and a role for blood group O in mediating the association. The 15 most significant RBC-associated ABO SNPs were also associated with five cardiometabolic traits, with discordance in the direction of effect between groups of traits, suggesting that ABO may act through more than one mechanism to influence cardiometabolic risk. PMID:27280446

  11. The Association between Arrhythmia and Helicobacter pylori Infection: A Meta-Analysis of Case-Control Studies

    PubMed Central

    Yan, Jin; She, Qiang; Zhang, Yifeng; Cui, Chang; Zhang, Guoxin

    2016-01-01

    Arrhythmia is a common disease around the world and Helicobacter pylori (H. pylori) is a bacterium infecting 28% to 84% of subjects, depending on the population tested. However, the implication of H. pylori in cardiac arrhythmia is poorly understood. We performed this meta-analysis with an aim to identify the association between arrhythmia and H. pylori. We searched PubMed, Embase, Web of Science, and the Cochrane library databases to select studies on the association between arrhythmia and H. pylori. In the arrhythmia group, 392 (58.1%) were H. pylori-positive and in the control group 640 (47.8%) were H. pylori-positive. Compared to the controls, the infection rate of H. pylori was higher in patients with arrhythmia than in controls (odds ratio (OR) = 1.797, 95% confidence interval (CI): 1.081–2.988, p < 0.05). Subgroup analysis indicated that H. pylori infection was a risk factor for atrial fibrillation in Asia and Africa. Therefore, a correlation between H. pylori infection and arrhythmia may exist and H. pylori eradication may decrease the occurrence of arrhythmia, especially in Asia and Africa. PMID:27854353

  12. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

    PubMed Central

    Elks, Cathy E.; Perry, John R.B.; Sulem, Patrick; Chasman, Daniel I.; Franceschini, Nora; He, Chunyan; Lunetta, Kathryn L.; Visser, Jenny A.; Byrne, Enda M.; Cousminer, Diana L.; Gudbjartsson, Daniel F.; Esko, Tõnu; Feenstra, Bjarke; Hottenga, Jouke-Jan; Koller, Daniel L.; Kutalik, Zoltán; Lin, Peng; Mangino, Massimo; Marongiu, Mara; McArdle, Patrick F.; Smith, Albert V.; Stolk, Lisette; van Wingerden, Sophie W.; Zhao, Jing Hua; Albrecht, Eva; Corre, Tanguy; Ingelsson, Erik; Hayward, Caroline; Magnusson, Patrik K.E.; Smith, Erin N.; Ulivi, Shelia; Warrington, Nicole M.; Zgaga, Lina; Alavere, Helen; Amin, Najaf; Aspelund, Thor; Bandinelli, Stefania; Barroso, Ines; Berenson, Gerald S.; Bergmann, Sven; Blackburn, Hannah; Boerwinkle, Eric; Buring, Julie E.; Busonero, Fabio; Campbell, Harry; Chanock, Stephen J.; Chen, Wei; Cornelis, Marilyn C.; Couper, David; Coviello, Andrea D.; d’Adamo, Pio; de Faire, Ulf; de Geus, Eco J.C.; Deloukas, Panos; Döring, Angela; Smith, George Davey; Easton, Douglas F.; Eiriksdottir, Gudny; Emilsson, Valur; Eriksson, Johan; Ferrucci, Luigi; Folsom, Aaron R.; Foroud, Tatiana; Garcia, Melissa; Gasparini, Paolo; Geller, Frank; Gieger, Christian; Gudnason, Vilmundur; Hall, Per; Hankinson, Susan E.; Ferreli, Liana; Heath, Andrew C.; Hernandez, Dena G.; Hofman, Albert; Hu, Frank B.; Illig, Thomas; Järvelin, Marjo-Riitta; Johnson, Andrew D.; Karasik, David; Khaw, Kay-Tee; Kiel, Douglas P.; Kilpeläinen, Tuomas O.; Kolcic, Ivana; Kraft, Peter; Launer, Lenore J.; Laven, Joop S.E.; Li, Shengxu; Liu, Jianjun; Levy, Daniel; Martin, Nicholas G.; McArdle, Wendy L.; Melbye, Mads; Mooser, Vincent; Murray, Jeffrey C.; Murray, Sarah S.; Nalls, Michael A.; Navarro, Pau; Nelis, Mari; Ness, Andrew R.; Northstone, Kate; Oostra, Ben A.; Peacock, Munro; Palmer, Lyle J.; Palotie, Aarno; Paré, Guillaume; Parker, Alex N.; Pedersen, Nancy L.; Peltonen, Leena; Pennell, Craig E.; Pharoah, Paul; Polasek, Ozren; Plump, Andrew S.; Pouta, Anneli; Porcu, Eleonora; Rafnar, Thorunn; Rice, John P.; Ring, Susan M.; Rivadeneira, Fernando; Rudan, Igor; Sala, Cinzia; Salomaa, Veikko; Sanna, Serena; Schlessinger, David; Schork, Nicholas J.; Scuteri, Angelo; Segrè, Ayellet V.; Shuldiner, Alan R.; Soranzo, Nicole; Sovio, Ulla; Srinivasan, Sathanur R.; Strachan, David P.; Tammesoo, Mar-Liis; Tikkanen, Emmi; Toniolo, Daniela; Tsui, Kim; Tryggvadottir, Laufey; Tyrer, Jonathon; Uda, Manuela; van Dam, Rob M.; van Meurs, Joyve B.J.; Vollenweider, Peter; Waeber, Gerard; Wareham, Nicholas J.; Waterworth, Dawn M.; Weedon, Michael N.; Wichmann, H. Erich; Willemsen, Gonneke; Wilson, James F.; Wright, Alan F.; Young, Lauren; Zhai, Guangju; Zhuang, Wei Vivian; Bierut, Laura J.; Boomsma, Dorret I.; Boyd, Heather A.; Crisponi, Laura; Demerath, Ellen W.; van Duijn, Cornelia M.; Econs, Michael J.; Harris, Tamara B.; Hunter, David J.; Loos, Ruth J.F.; Metspalu, Andres; Montgomery, Grant W.; Ridker, Paul M.; Spector, Tim D.; Streeten, Elizabeth A.; Stefansson, Kari; Thorsteinsdottir, Unnur; Uitterlinden, André G.; Widen, Elisabeth; Murabito, Joanne M.; Ong, Ken K.; Murray, Anna

    2011-01-01

    To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P=5.4×10−60) and 9q31.2 (P=2.2×10−33), we identified 30 novel menarche loci (all P<5×10−8) and found suggestive evidence for a further 10 loci (P<1.9×10−6). New loci included four previously associated with BMI (in/near FTO, SEC16B, TRA2B and TMEM18), three in/near other genes implicated in energy homeostasis (BSX, CRTC1, and MCHR2), and three in/near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and MAGENTA pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing. PMID:21102462

  13. Association between Dietary Vitamin A Intake and the Risk of Glioma: Evidence from a Meta-analysis

    PubMed Central

    Lv, Wen; Zhong, Xian; Xu, Lingmin; Han, Weidong

    2015-01-01

    The results from epidemiological studies between dietary vitamin A intake and glioma risk is not consistent. Thus, a meta-analysis was conducted to confirm the exact relationship between them. PubMed and Web of Knowledge were used to search the relevant articles up to May 2015. Pooled relative risk (RR) with 95% confidence interval (CI)was calculated using random-effect model. Egger’s test was used to assess the small-study effect. At the end, seven articles with eight case-control studies involving 1841 glioma cases and 4123 participants were included. Our study indicated that highest category of dietary vitamin A intake was significantly associated with reduced risk of glioma (RR = 0.80, 95% CI = 0.62–0.98, p = 0.014, I2 = 54.9%). Egger’s test did not find any publication bias. In conclusion, our study indicated that higher category of dietary vitamin A intake could reduce the glioma risk. However, we could not do a dose-response analysis for vitamin A intake with glioma risk due to the limited data in each reported individual article. Due to this limitation, further studies with detailed dose, cases and person-years for each category is wanted to assess this dose-response association. PMID:26516909

  14. Ramadan fasting is not usually associated with the risk of cardiovascular events: A systematic review and meta-analysis

    PubMed Central

    Turin, Tanvir C.; Ahmed, Salim; Shommu, Nusrat S.; Afzal, Arfan R.; Al Mamun, Mohammad; Qasqas, Mahdi; Rumana, Nahid; Vaska, Marcus; Berka, Noureddine

    2016-01-01

    Over one billion Muslims worldwide fast during the month of Ramadan. Ramadan fasting brings about some changes in the daily lives of practicing Muslims, especially in their diet and sleep patterns, which are associated with the risk of cardiovascular diseases. Over the years, many original studies have made the effort to identify the possible impact of the Ramadan fast on cardiovascular diseases. This systematic review and meta-analysis is an attempt to present the summary of key findings from those articles and an appraisal of selected literature. A systematic search using keywords of “;Ramadan fasting” and “;cardiovascular diseases” was conducted in primary research article and gray-literature repositories, in combination with hand searching and snow balling. Fifteen studies were finally selected for data extraction on the outcomes of stroke, myocardial infarction, and congestive heart failure. The analysis revealed that the incidence of cardiovascular events during the Ramadan fast was similar to the nonfasting period. Ramadan fast is not associated with any change in incidence of acute cardiovascular disease. PMID:27186152

  15. Quantifying the strength of the associations of prototype perceptions with behaviour, behavioural willingness and intentions: a meta-analysis.

    PubMed

    van Lettow, Britt; de Vries, Hein; Burdorf, Alex; van Empelen, Pepijn

    2016-01-01

    Prototypes (i.e., social images representing perceptions of typical persons engaging in or refraining from certain behaviour) have been shown to explain health-related behaviours. The present meta-analysis quantified the strength of the associations of prototype perceptions with health motivation and behaviour. Specifically, the analysis addressed (i) the relationship of prototype favourability (i.e., degree of likability) and similarity (i.e., perceived resemblance to the self) with behaviour, willingness and intentions; (ii) the effect of the interaction between favourability and similarity; and (iii) the extent to which health-risk and health-protective prototypes differed in their association with these outcomes. A total of 80 independent studies were identified based on 69 articles. The results indicated that prototype favourability and similarity were related to behaviour, intentions and willingness with small-to-medium effect sizes (r+ = 0.12-0.43). Direct measures of prototype perceptions generally produced larger effects than indirect measures. The interaction between favourability and similarity produced small-to-large effect sizes (r+ = .22-.54). The results suggest that both health-risk and health-protective prototypes might be useful targets for interventions (r+ = .22-.54). In order to increase health-protective behaviours, intentions and behaviour could be targeted by increasing similarity to health-protective prototypes. Health-risk behaviour might be decreased by targeting willingness by modifying health-risk prototype favourability and similarity.

  16. The Association between Arrhythmia and Helicobacter pylori Infection: A Meta-Analysis of Case-Control Studies.

    PubMed

    Yan, Jin; She, Qiang; Zhang, Yifeng; Cui, Chang; Zhang, Guoxin

    2016-11-16

    Arrhythmia is a common disease around the world and Helicobacter pylori (H. pylori) is a bacterium infecting 28% to 84% of subjects, depending on the population tested. However, the implication of H. pylori in cardiac arrhythmia is poorly understood. We performed this meta-analysis with an aim to identify the association between arrhythmia and H. pylori. We searched PubMed, Embase, Web of Science, and the Cochrane library databases to select studies on the association between arrhythmia and H. pylori. In the arrhythmia group, 392 (58.1%) were H. pylori-positive and in the control group 640 (47.8%) were H. pylori-positive. Compared to the controls, the infection rate of H. pylori was higher in patients with arrhythmia than in controls (odds ratio (OR) = 1.797, 95% confidence interval (CI): 1.081-2.988, p < 0.05). Subgroup analysis indicated that H. pylori infection was a risk factor for atrial fibrillation in Asia and Africa. Therefore, a correlation between H. pylori infection and arrhythmia may exist and H. pylori eradication may decrease the occurrence of arrhythmia, especially in Asia and Africa.

  17. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies.

    PubMed

    Elks, Cathy E; Perry, John R B; Sulem, Patrick; Chasman, Daniel I; Franceschini, Nora; He, Chunyan; Lunetta, Kathryn L; Visser, Jenny A; Byrne, Enda M; Cousminer, Diana L; Gudbjartsson, Daniel F; Esko, Tõnu; Feenstra, Bjarke; Hottenga, Jouke-Jan; Koller, Daniel L; Kutalik, Zoltán; Lin, Peng; Mangino, Massimo; Marongiu, Mara; McArdle, Patrick F; Smith, Albert V; Stolk, Lisette; van Wingerden, Sophie H; Zhao, Jing Hua; Albrecht, Eva; Corre, Tanguy; Ingelsson, Erik; Hayward, Caroline; Magnusson, Patrik K E; Smith, Erin N; Ulivi, Shelia; Warrington, Nicole M; Zgaga, Lina; Alavere, Helen; Amin, Najaf; Aspelund, Thor; Bandinelli, Stefania; Barroso, Inês; Berenson, Gerald S; Bergmann, Sven; Blackburn, Hannah; Boerwinkle, Eric; Buring, Julie E; Busonero, Fabio; Campbell, Harry; Chanock, Stephen J; Chen, Wei; Cornelis, Marilyn C; Couper, David; Coviello, Andrea D; d'Adamo, Pio; de Faire, Ulf; de Geus, Eco J C; Deloukas, Panos; Döring, Angela; Smith, George Davey; Easton, Douglas F; Eiriksdottir, Gudny; Emilsson, Valur; Eriksson, Johan; Ferrucci, Luigi; Folsom, Aaron R; Foroud, Tatiana; Garcia, Melissa; Gasparini, Paolo; Geller, Frank; Gieger, Christian; Gudnason, Vilmundur; Hall, Per; Hankinson, Susan E; Ferreli, Liana; Heath, Andrew C; Hernandez, Dena G; Hofman, Albert; Hu, Frank B; Illig, Thomas; Järvelin, Marjo-Riitta; Johnson, Andrew D; Karasik, David; Khaw, Kay-Tee; Kiel, Douglas P; Kilpeläinen, Tuomas O; Kolcic, Ivana; Kraft, Peter; Launer, Lenore J; Laven, Joop S E; Li, Shengxu; Liu, Jianjun; Levy, Daniel; Martin, Nicholas G; McArdle, Wendy L; Melbye, Mads; Mooser, Vincent; Murray, Jeffrey C; Murray, Sarah S; Nalls, Michael A; Navarro, Pau; Nelis, Mari; Ness, Andrew R; Northstone, Kate; Oostra, Ben A; Peacock, Munro; Palmer, Lyle J; Palotie, Aarno; Paré, Guillaume; Parker, Alex N; Pedersen, Nancy L; Peltonen, Leena; Pennell, Craig E; Pharoah, Paul; Polasek, Ozren; Plump, Andrew S; Pouta, Anneli; Porcu, Eleonora; Rafnar, Thorunn; Rice, John P; Ring, Susan M; Rivadeneira, Fernando; Rudan, Igor; Sala, Cinzia; Salomaa, Veikko; Sanna, Serena; Schlessinger, David; Schork, Nicholas J; Scuteri, Angelo; Segrè, Ayellet V; Shuldiner, Alan R; Soranzo, Nicole; Sovio, Ulla; Srinivasan, Sathanur R; Strachan, David P; Tammesoo, Mar-Liis; Tikkanen, Emmi; Toniolo, Daniela; Tsui, Kim; Tryggvadottir, Laufey; Tyrer, Jonathon; Uda, Manuela; van Dam, Rob M; van Meurs, Joyce B J; Vollenweider, Peter; Waeber, Gerard; Wareham, Nicholas J; Waterworth, Dawn M; Weedon, Michael N; Wichmann, H Erich; Willemsen, Gonneke; Wilson, James F; Wright, Alan F; Young, Lauren; Zhai, Guangju; Zhuang, Wei Vivian; Bierut, Laura J; Boomsma, Dorret I; Boyd, Heather A; Crisponi, Laura; Demerath, Ellen W; van Duijn, Cornelia M; Econs, Michael J; Harris, Tamara B; Hunter, David J; Loos, Ruth J F; Metspalu, Andres; Montgomery, Grant W; Ridker, Paul M; Spector, Tim D; Streeten, Elizabeth A; Stefansson, Kari; Thorsteinsdottir, Unnur; Uitterlinden, André G; Widen, Elisabeth; Murabito, Joanne M; Ong, Ken K; Murray, Anna

    2010-12-01

    To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.

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

    PubMed

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

    2017-03-01

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

  19. Association between transcription factor 7-like 2 rs7903146 polymorphism and diabetic retinopathy in type 2 diabetes mellitus: A meta-analysis.

    PubMed

    Ding, Yuzhi; Hu, Zizhong; Yuan, Songtao; Xie, Ping; Liu, Qinghuai

    2015-11-01

    As one of the vascular complications of type 2 diabetes mellitus, the incidence of diabetes retinopathy is greatly increasing worldwide. Both genetic and environmental factors are involved in the pathologies. A meta-analysis was conducted to assess the association between transcription factor 7-like 2 polymorphism (rs7903146) and type 2 diabetic retinopathy. Published literature from PubMed, Web of Science and China National Knowledge Infrastructure were retrieved. Pooled odds ratios with 95% confidence intervals were calculated to estimate the strength of the association. Eight studies including 6422 participants were included in the final meta-analysis. Our analysis provides substantial evidence that the rs7903146 variant is significantly associated with the risk of diabetic retinopathy in Caucasian populations while not in East Asian populations. The variant of rs7903146 appeared more likely to be a promising genetic biomarker of diabetic retinopathy in Caucasians.

  20. Association of Renalase SNPs rs2296545 and rs2576178 with the Risk of Hypertension: A Meta-Analysis

    PubMed Central

    Ma, Wang-Ge; Yan, Ding-Yi; Zheng, Wen-Ling; Chu, Chao; Guo, Tong-Shuai; Yuan, Zu-Yi; Mu, Jian-Jun

    2016-01-01

    Background/Aims Two renalase single nucleotide polymorphisms (SNPs) rs2296545 and rs2576178 have been reported to be associated with the susceptibility to hypertension (HT). Given the inconsistent results, we conducted a meta-analysis to assess the association between these two SNPs and the risk of HT. Methods Electronic databases were systematically searched to find relevant studies. Subgroup analysis was conducted according to the different concomitant diseases and ethnicities in the study population. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using fixed-effect or random-effect models. Results A total of six case–control studies on rs2296545 and six studies on rs2576178 were included. In the combined analysis, results showed a significant association between SNP rs2296545 and risk of HT in all genetic models (dominant model CG+CC/GG: OR = 1.43, 95% CI = 1.24–1.65; recessive model CC/CG+GG: OR = 1.36, 95% CI = 1.09–1.69; codominant model CC/GG: OR = 1.63, 95% CI = 1.20–2.20, CG/GG: OR = 1.30, 95% CI = 1.12–1.52; allelic model C/G: OR = 1.29, 95% CI = 1.10–1.51). In subgroup analysis, we observed a significant association between rs2296545 and risk of essential HT. Although we did not observe an association between rs2576178 polymorphism and HT in the combined analysis, an increased risk was observed in the essential HT patients versus healthy controls (subgroup 1) analysis under the dominant, recessive, and codominant genetic models. Conclusions Renalase gene rs2296545 polymorphism is significantly associated with increased risk of HT, whereas rs2576178 polymorphism may not be associated with the susceptibility to HT. PMID:27434211

  1. Association between the CTLA-4 +49A/G polymorphism and Graves' disease: A meta-analysis.

    PubMed

    Si, Xiaoyu; Zhang, Xiufeng; Tang, Wenru; Luo, Ying

    2012-09-01

    The +49A/G polymorphism of the cytotoxic T-lymphocyte-associated antigen-4 gene (CTLA-4) has been associated with Graves' disease (GD). However, results have been inconsistent. The aim of this study was to quantitatively summarize the evidence for CTLA-4 +49A/G polymorphism and GD. Electronic search of PubMed was conducted to select studies. Case-control studies containing available genotype frequencies of CTLA-4 +49 were chosen, and Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association. Forty-two case-control studies including 8,288 cases and 9,372 controls were identified. Three studies were eliminated from the total 42 studies due to a p-value <0.05 (p-value for Hardy-Weinberg equilibrium in control group) in these studies which induced significant publication bias. The overall results suggested that the variant genotypes were highly associated (p<0.01) with GD risk in all genetic models (additive model: OR, 1.443; 95% CI, 1.319-1.578; p<0.001; recessive model: OR, 1.589; 95% CI, 1.396-1.808; p<0.001; dominant model: OR, 1.621; 95% CI, 1.430-1.837; p<0.001). Similarly, in the subgroup analyses for ethnicity (Caucasian, Asian), the results were positive. This meta-analysis suggests that the CTLA-4 +49A/G polymorphism is highly associated (p<0.01) with increased risk of GD, especially in Caucasians and Asians. To validate this association, further studies with larger participants worldwide are needed to examine associations between this polymorphism and GD.

  2. Associations between TNF-α polymorphisms and susceptibility to rheumatoid arthritis and vitiligo: a meta-analysis.

    PubMed

    Lee, Y H; Bae, S C

    2015-05-25

    We investigated whether the tumor necrosis factor-a (TNF-α) promoter -238 A/G and -308 A/G polymorphisms are associated with rheumatoid arthritis (RA) and vitiligo susceptibility. MEDLINE and EMBASE databases and a manual search were used to identify articles in which TNF-α polymorphisms were determined in RA or vitiligo patients and controls. Meta-analysis was used to examine the associations between the TNF-α -238 A/G polymorphism and RA and vitiligo using the allelic contrast and dominant models. Fifteen studies (10 RA and 5 vitiligo) involving 3678 cases and 4400 controls were considered. We observed an association between the TNF-α -238 A allele and RA when all subjects were considered [odds ratio (OR) = 0.686, 95% confidence interval (CI) = 0.476-0.968, P = 0.043]. After stratification by ethnicity, we found no association between the TNF-α -238 A allele and RA in European or Asian populations. We observed no association between the TNF-α -308 A allele and vitiligo (OR = 1.787, 95%CI = 0.894-3.573, P = 0.101). However, the adjusted OR by the trim-and-fill technique was significant (OR = 2.064, 95%CI = 1.138- 3.743). After stratification by geographic continent, the TNF-α -308 A allele was significantly associated with vitiligo in Middle Eastern populations (OR = 1.569, 95%CI = 1.224-2.013, P = 3.8 x 10(-5)). The TNF-α -238 A/G polymorphism was associated with RA susceptibility, and the TNF-α -308 A/G polymorphism may be a significant risk factor for vitiligo in Middle Eastern populations.

  3. Association between XRCC3 Thr241Met polymorphism and risk of brain tumors: a meta-analysis.

    PubMed

    Liu, Jun; Zhou, Zheng; Lai, Ting; Yin, Jinbo

    2014-02-01

    X-ray repair cross-complementing group 3 (XRCC3) plays an important role in the process of homologous recombination repair for DNA double-strand breaks which further maintains the stability of the genome. XRCC3 Thr241Met polymorphism has been indicated in the development of cancers, but the association of the XRCC3 Thr241Met polymorphism with risk of brain tumors is still unclear owing to the conflicting findings from previous studies. We performed a meta-analysis to provide a better understanding on the association between the XRCC3 Thr241Met polymorphism and risk of brain tumors. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was used to assess the association. Thirteen case-control studies involving a total of 4,984 cases and 7,472 controls were included. Overall, there was no statistically significant association between the XRCC3 Thr241Met polymorphism and risk of brain tumors under all contrast models. Subgroup analysis by race suggested that the XRCC3 Thr241Met polymorphism was associated with increased risk of brain tumors in Asians under all four contrast models (Met vs. Thr: OR = 1.22, 95 % CI 1.09-1.36, P < 0.01; MetMet vs. ThrThr: OR = 1.89, 95 % CI 1.38-2.57, P < 0.01; MetMet vs. ThrThr/ThrMet: OR = 1.78, 95 % CI 1.31-2.40, P < 0.01; and MetMet vs. ThrThr/ThrMet: OR = 1.19, 95 % CI 1.04-1.36, P = 0.01). However, there was no significant association between the XRCC3 Thr241Met polymorphism and risk of brain tumors in Caucasians. Therefore, the XRCC3 Thr241Met polymorphism is associated with increased risk of brain tumors, especially in Asians.

  4. Association between the CD24 Ala57Val polymorphism and risk for multiple sclerosis and systemic lupus erythematosus: a meta-analysis

    PubMed Central

    Huang, Jian; Yang, Yaqi; Liang, Zibin; Kang, Miaomiao; Kuang, Ying; Li, Feng

    2015-01-01

    The cluster of differentiation 24 (CD24) Ala57Val polymorphism has been implicated as a risk factor for multiple sclerosis (MS) and systemic lupus erythematosus (SLE); however, genetic studies have produced controversial results. A meta-analysis was performed on this topic. We used odds ratio (OR) and 95% confidence interval (95% CI) to investigate the strength of association. Eleven studies from nine publications consisting of 2466 cases and 2650 controls were included. The results suggested that the CD24 Val/Val genotypes were associated with an increased risk of MS in all study subjects and Caucasians (OR = 2.28, 95% CI: 1.68–3.10, Pz < 0.001 and OR = 2.30, 95% CI: 1.66–3.20, Pz < 0.001, respectively). Sensitivity analysis showed that no individual study was found to be significantly biasing the pooled results. Although meta-analysis also suggested an association between the CD24 Val/Val genotypes and SLE risk in Caucasians (OR = 1.71, 95% CI: 1.31–2.24, Pz < 0.001), sensitivity analysis demonstrated that the association was not statistically significant after removing a Spanish study. In conclusion, this meta-analysis suggests that the CD24 Ala57Val polymorphism is associated with an increased risk of MS in Caucasians. However, the available evidence is not sufficient to support an association between the CD24 Ala57Val polymorphism and SLE risk. PMID:25830931

  5. Intraoperative Ultrasound Guidance Is Associated with Clear Lumpectomy Margins for Breast Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Ding, Qiang; Dai, Juncheng; Ling, Lijun; Chen, Lin; Zha, Xiaoming; Liu, Xiaoan; Zhou, Wenbin; Wang, Shui

    2013-01-01

    Purpose Margin status is one of the most important predictors of local recurrence after breast conserving surgery (BCS). Intraoperative ultrasound guidance (IOUS) has the potential to improve surgical accuracy for breast cancer. The purpose of the present meta-analysis was to determine the efficacy of IOUS in breast cancer surgery and to compare the margin status to that of the more traditional Guide wire localization (GWL) or palpation-guidance. Methods We searched the database of PubMed for prospective and retrospective studies about the impact of IOUS on margin status of breast cancer, and a meta-analysis was conducted. Results Of the 13 studies included, 8 were eligible for the impact of IOUS on margin status of non-palpable breast cancers, 4 were eligible for palpable breast cancers, and 1 was for both non-palpable and palpable breast cancers. The rate of negative margins of breast cancers in IOUS group was significantly higher than that in control group without IOUS (risk ratio (RR)  = 1.37, 95% confidence interval (CI)  = 1.18–1.59 from 7 prospective studies, odds ratio (OR)  = 2.75, 95% CI  = 1.66–4.55 from 4 retrospective studies). For non-palpable breast cancers, IOUS-guidance enabled a significantly higher rate of negative margins than that of GWL-guidance (RR  = 1.26, 95% CI  = 1.09–1.46 from 6 prospective studies; OR  = 1.45, 95% CI  = 0.86–2.43 from 2 retrospective studies). For palpable breast cancers, relative to control group without IOUS, the RR for IOUS associated negative margins was 2.36 (95% CI  = 1.26–4.43) from 2 prospective studies, the OR was 2.71 (95% CI  = 1.25–5.87) from 2 retrospective studies. Conclusion This study strongly suggests that IOUS is an accurate method for localization of non-palpable and palpable breast cancers. It is an efficient method of obtaining high proportion of negative margins and optimum resection volumes in patients undergoing BCS. PMID:24073200

  6. Testing the association of novel meta-analysis-derived diabetes risk genes with type II diabetes and related metabolic traits in Asian Indian Sikhs.

    PubMed

    Sanghera, Dharambir K; Been, Latonya; Ortega, Lyda; Wander, Gurpreet S; Mehra, Narinder K; Aston, Christopher E; Mulvihill, John J; Ralhan, Sarju

    2009-03-01

    A recent meta-analysis on three genome-wide association (GWA) scans identified six loci (NOTCH2, THADA, ADAMTS9, JAZF1, CDC123/CAMKID and TSPAN8/LGRS) highly associated with type II diabetes (T2D) in Caucasians. This investigation seeks to confirm this association with diabetes and related metabolic traits in Khatri Sikh diabetics of North India. We genotyped highly significant variants from each locus in a case-control cohort consisting of 680 T2D cases and 637 normoglycemic (NG) controls. Only CDC123/CAMKID (rs12779790) replicated earlier evidence of association with T2D under a dominant model (odds ratio (OR): 1.27; 95% confidence interval (CI): 1.02-1.57; P=0.031) during initial testing. However, we could not confirm this association using multiple testing corrections. In a multiple linear-regression analysis, the same variant in the CDC123/CAMKID revealed a marked decrease in fasting insulin levels among 'G' (risk) allele carriers independently in NG controls (P=0.030) and in T2D cases (P=0.009), as well as in the combined sample (P=0.003) after adjusting for covariates. Evidence of impaired beta-cell function was also observed among 'G' (risk) allele carriers in T2D cases (P=0.008) and in a combined cohort (P=0.026). Our data could not confirm the role of the remaining variants with risk either for T2D or quantitative phenotypes measuring insulin secretion or insulin resistance. These findings suggest that CDC123/CAMKID could be a major risk factor for the development of T2D in Sikhs by affecting beta-cell function. To our knowledge, this is the first study reporting the role of recently emerging loci in this high-risk population from the South Asian subcontinent.

  7. Association between LGALS2 3279C>T and coronary artery disease: A case-control study and a meta-analysis

    PubMed Central

    LIAN, JIANGFANG; FANG, PEILIANG; DAI, DONGJUN; BA, YANNA; YANG, XI; HUANG, XIAOYAN; LI, JUNXIN; CHEN, XIAOLIANG; GUO, JIAN; GUAN, FENG; PENG, PING; ZHAO, RUOCHI; ZHANG, SHANGSHI; GAO, FANG; TANG, LINLIN; ZHANG, CHENG; JI, HUIHUI; HONG, QINGXIAO; YE, HUADAN; XU, LIMIN; ZHONG, QILONG; LIU, PANPAN; ZHOU, JIANQING; DUAN, SHIWEI

    2014-01-01

    Coronary artery disease (CAD) has become the main cause of mortality worldwide. Lectin galactoside-binding soluble-2 (LGALS2) is involved in the cytokine lymphotoxin-α (LTA) cascade that may influence the progress of CAD. The aim of the present study was to assess the association between the LGALS2 3279C>T (rs7291467) polymorphism and CAD. A total of 562 cases and 572 controls were recruited to examine the association. A systematic meta-analysis was performed to evaluate the contribution of LGALS2 3279C>T polymorphism to the risk of CAD among 12,093 cases and 11,020 controls. There was no significant association found in the present case-control study. However, the meta-analysis showed that LGALS2 3279C>T played a protective role in CAD [P=0.008, odds ratio (OR), 0.90; 95% confidence interval (95% CI), 0.82–0.97] and particularly in the Asian population (P=0.006; OR, 0.82; 95% CI, 0.71–0.94). The present case-control study did not find a significant association between LGALS2 3279C>T and CAD in the Eastern Han Chinese population. However, the meta-analysis indicated that LGALS2 3279C>T played a protective role in CAD, suggesting an ethnic difference in the association of the locus with CAD. PMID:25279163

  8. Tumor necrosis factor-alpha promoter polymorphism 308 G/A is not significantly associated with esophageal cancer risk: a meta-analysis.

    PubMed

    Luo, Ming; Yang, Yuan; Luo, Dongmei; Liu, Liang; Zhang, Yuening; Xiao, Feifan; Yang, Jingcheng; Zhang, Chengdong; Fu, Shen; Luo, Zhiguo

    2016-11-29

    Many studies have investigated the association between Tumor necrosis factor-α-308 G>A (rs1800629) and the risk of esophageal cancer. However, their results are inconsistent. Therefore, we performed a meta-analysis of available data to investigate any possible association between this polymorphism and esophageal cancer risk. We searched PubMed, EMBASE, Web of Science, and the CNKI database for articles published up to 2016. Crude and adjusted odds ratio with 95% confidence intervals were calculated using fixed or random effects models. We used a dominant model (GA+AA vs GG), a recessive model (AA vs GG+GA), an over-dominant model (GG+AA vs GA), and allele frequency (G vs A) to identify any association. Eleven studies with 5617 participants were included in the meta-analysis. Our results suggest that TNF-α-308 G>A (rs1800629) is not significantly associated with a risk of esophageal squamous cell carcinoma and esophageal adenocarcinoma. For genetic association studies, negative results of meta-analysis have a high level of evidence, and these results are important in this era of high-throughput sequencing-based precision medicine.

  9. Clinicopathological and prognostic significance of metastasis-associated in colon cancer-1 (MACC1) overexpression in colorectal cancer: a meta-analysis

    PubMed Central

    Zhao, Yang; Dai, Cong; Wang, Meng; Kang, Huafeng; Lin, Shuai; Yang, Pengtao; Liu, Xinghan; Liu, Kang; Xu, Peng; Zheng, Yi; Li, Shanli; Dai, Zhijun

    2016-01-01

    Metastasis-associated in colon cancer-1 (MACC1) has been reported to be overexpressed in diverse human malignancies, and the increasing amount of evidences suggest that its overexpression is associated with the development and progression of many human tumors. However, the prognostic and clinicopathological value of MACC1 in colorectal cancer remains inconclusive. Therefore, we conducted this meta-analysis to investigate the effect of MACC1 overexpression on clinicopathological features and survival outcomes in colorectal cancer. PubMed, CNKI, and Wanfang databases were searched for relevant articles published update to December 2015. Correlation of MACC1 expression level with overall survival (OS), disease-free survival (DFS), and clinicopathological features were analyzed. In this meta-analysis, fifteen studies with a total of 2,161 colorectal cancer patients were included. Our results showed that MACC1 overexpression was significantly associated with poorer OS and DFS. Moreover, MACC1 overexpression was significantly associated with gender, localization, TNM stage, T stage, and N stage. Together, our meta-analysis showed that MACC1 overexpression was significantly associated with poor survival rates, regional invasion and lymph-node metastasis. MACC1 expression level can serve as a novel prognostic factor in colorectal cancer patients. PMID:27542234

  10. Tumor necrosis factor-alpha promoter polymorphism 308 G/A is not significantly associated with esophageal cancer risk: a meta-analysis

    PubMed Central

    Zhang, Yuening; Xiao, Feifan; Yang, Jingcheng; Zhang, Chengdong; Fu, Shen; Luo, Zhiguo

    2016-01-01

    Many studies have investigated the association between Tumor necrosis factor-α-308 G>A (rs1800629) and the risk of esophageal cancer. However, their results are inconsistent. Therefore, we performed a meta-analysis of available data to investigate any possible association between this polymorphism and esophageal cancer risk. We searched PubMed, EMBASE, Web of Science, and the CNKI database for articles published up to 2016. Crude and adjusted odds ratio with 95% confidence intervals were calculated using fixed or random effects models. We used a dominant model (GA+AA vs GG), a recessive model (AA vs GG+GA), an over-dominant model (GG+AA vs GA), and allele frequency (G vs A) to identify any association. Eleven studies with 5617 participants were included in the meta-analysis. Our results suggest that TNF-α-308 G>A (rs1800629) is not significantly associated with a risk of esophageal squamous cell carcinoma and esophageal adenocarcinoma. For genetic association studies, negative results of meta-analysis have a high level of evidence, and these results are important in this era of high-throughput sequencing-based precision medicine. PMID:27821804

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

    PubMed Central

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

    2016-01-01

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

  12. The SNP rs931794 in 15q25.1 Is Associated with Lung Cancer Risk: A Hospital-Based Case-Control Study and Meta-Analysis

    PubMed Central

    Hu, Weiguo; Lu, Xuzai; Wang, Zhenling; Gong, Hongyun; Xu, Tangpeng; Chen, Xueqin; Xu, Bin; Liu, Cheng; Sun, Yun; Gong, Yajie; Yang, Yang; Zhu, Ying

    2015-01-01

    Background Lung cancer is one of the most common human malignant diseases and the leading cause of cancer death worldwide. The rs931794, a SNP located in 15q25.1, has been suggested to be associated with lung cancer risk. Nevertheless, several genetic association studies yielded controversial results. Methods and Findings A hospital-based case-control study involving 611 cases and 1062 controls revealed the variant of rs931794 was related to increased lung cancer risk. Stratified analyses revealed the G allele was significantly associated with lung cancer risk among smokers. Following meta-analysis including 6616 cases and 7697 controls confirmed the relevance of rs931794 variant with increased lung cancer risk once again. Heterogeneity should be taken into account when interpreting the consequences. Stratified analysis found ethnicity, histological type and genotyping method were not the sources of between-study heterogeneity. Further sensitivity analysis revealed that the study “Hsiung et al (2010)” might be the major contributor to heterogeneity. Cumulative meta-analysis showed the trend was increasingly obvious with adding studies, confirming the significant association. Conclusions Results from our current case-control study and meta-analysis offered insight of association between rs931794 and lung cancer risk, suggesting the variant of rs931794 might be related with increased lung cancer risk. PMID:26079375

  13. Association of telomerase reverse transcriptase promoter mutations with clinicopathological features and prognosis of thyroid cancer: a meta-analysis

    PubMed Central

    Su, Xingyun; Jiang, Xiaoxia; Wang, Weibin; Wang, Haiyong; Xu, Xin; Lin, Aihui; Teng, Xiaodong; Wu, Huiling; Teng, Lisong

    2016-01-01

    The clinicopathological and prognostic significance of telomerase reverse transcriptase (TERT) promoter mutations have been widely investigated in thyroid cancer; however, the results are still discrepant. Systematic searches were performed in PubMed, Web of Science, Scopus, Ovid, and the Cochran Library databases for relevant articles prior to April 2016. Mutation rates were synthesized by R statistical software. The odds ratio or standardized mean difference with 95% confidence interval was pooled by Stata. A total of 22 studies with 4,907 cases were included in this meta-analysis. TERT promoter mutations tended to present in aggressive histological types including poorly differentiated thyroid cancer (33.37%), anaplastic thyroid cancer (38.69%), and tall-cell variant papillary thyroid cancer (30.23%). These promoter mutations were likely to exist in older patients and males and were well associated with larger tumor size, extrathyroidal extension, vascular invasion, lymph node metastasis, distant metastasis, advanced tumor stage, disease recurrence/persistence, and mortality. In addition, TERT promoter mutations (especially C228T) tended to coexist with BRAFV600E mutation, which indicated more aggressive tumor behavior. Therefore, TERT promoter mutations may be promising biomarkers for early diagnosis, risk stratification, prognostic prediction, and management of thyroid cancer. PMID:27956840

  14. [Diagnostic value of MRI versus 99Tcm-MDP bone scan in osseous metastasis of prostate cancer: a meta-analysis].

    PubMed

    Shen, Guohua; Zhou, Luyi; Jia, Zhiyun; Zhang, Wenjie; Wang, Qiao; Deng, Houfu

    2014-08-01

    This paper is aimed to assess the diagnostic value of MRI versus 99 Tcm-methylene diphosphonate (99 Tcm- MDP) bone scan (BS) for osseous metastases in patients with prostate cancer. The computer-based retrieval was conducted on PubMed, EMBASE, EBSCO, Web of Knowledge, the Cochrane Library and Ovid data bases to search for trials about diagnosing osseous metastases of prostate cancer with MRI and 99Tc"m-MDP BS. Selected with time acceptance and time exclusion criteria, the data quality were evaluated with QUADAS quality assessment tool and collected. We used the Meta-Disc software to conduct meta-analysis, and then calculated the pooled sensitivity, specificity and diagnostic odds ratio (DOR), drew the summary receiving operating characteristic (SROC) curve, and measured the area under curve (AUC) and Q value. Then five studies were included, involving 353 patients. The pooled sensitivity of MRI and BS was 0. 95 (95% CI 0. 90~0. 98) and 0. 67 (95% CI 0. 58~0. 75), respectively. The pooled specificity was 0. 97 (95% CI 0. 94~0. 99) and 0. 88 (95% CI 0. 83~0. 91), respectively. The pooled DOR was 402.99 (95% CI 119. 05 ~1364. 15) and 23. 85 (95% CI 1. 32~431. 48), respectively. The AUC was 0. 990 1 and 0. 624 1, respectively. The Q was 0. 958 7 and 0. 593 8. It can well be concluded that MRI is more effective than 99 Tcm-MDP BS in the diagnosis of osseous metastases in patients with prostate cancer.

  15. Association of personality with the development and persistence of obesity: a meta-analysis based on individual-participant data.

    PubMed

    Jokela, M; Hintsanen, M; Hakulinen, C; Batty, G D; Nabi, H; Singh-Manoux, A; Kivimäki, M

    2013-04-01

    Personality is thought to affect obesity risk but before such information can be incorporated into prevention and intervention plans, robust and converging evidence concerning the most relevant personality traits is needed. We performed a meta-analysis based on individual-participant data from nine cohort studies to examine whether broad-level personality traits predict the development and persistence of obesity (n = 78,931 men and women; mean age 50 years). Personality was assessed using inventories of the Five-Factor Model (extraversion, neuroticism, agreeableness, conscientiousness and openness to experience). High conscientiousness - reflecting high self-control, orderliness and adherence to social norms - was associated with lower obesity risk across studies (pooled odds ratio [OR] = 0.84; 95% confidence interval [CI] = 0.80-0.88 per 1 standard deviation increment in conscientiousness). Over a mean follow-up of 5.4 years, conscientiousness predicted lower obesity risk in initially non-obese individuals (OR = 0.88, 95% CI = 0.85-0.92; n = 33,981) and was associated with greater likelihood of reversion to non-obese among initially obese individuals (OR = 1.08, 95% CI = 1.01-1.14; n = 9,657). Other personality traits were not associated with obesity in the pooled analysis, and there was substantial heterogeneity in the associations between studies. The findings indicate that conscientiousness may be the only broad-level personality trait of the Five-Factor Model that is consistently associated with obesity across populations.

  16. Association between Tumor Necrosis Factor-α rs1800629 Polymorphism and Risk of Asthma: A Meta-Analysis

    PubMed Central

    Yang, Guangdie; Chen, Junjun; Xu, Fei; Bao, Zhang; Yao, Yake; Zhou, Jianying

    2014-01-01

    Objective The purpose of this study was to explore the association between the TNF-α rs1800629 (also refers as -308G/A) polymorphism and asthma susceptibility. Methods We searched the Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Wanfang databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association. Results A total of 34 studies involving 5477 asthma patients and 5962 controls were included in present study. The results indicated that TNF-α rs1800629 polymorphism was significantly associated with asthma risk in a recessive genetic model (OR = 1.46, 95% CI 1.21–1.76, P<0.0001). Subgroup analyses found that the TNF-α rs1800629 polymorphism was significantly associated with asthma risk in West Asians and South Asians (OR = 2.47, 95% CI = 1.48–4.12, P = 0.0005; OR = 1.83, 95% CI = 1.42–2.36, P<0.00001), but not East Asians and Caucasians. Furthermore, significant association also was observed in allergic asthma (OR = 1.51, 95% CI = 1.24–1.83, P<0.0001), adults and children (OR = 1.43, 95 CI% = 1.07–1.91, P = 0.02; OR = 1.57, 95% CI = 1.19–2.06, P = 0.001). Conclusions This meta-analysis suggested that the rs1800629 polymorphism in TNF-α was a risk factor for asthma. PMID:24936650

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

    PubMed

    Marx, Robert A; Kettrey, Heather Hensman

    2016-07-01

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

  18. Dose-response of serum 25-hydroxyvitamin D in association with risk of colorectal cancer: A meta-analysis.

    PubMed

    Garland, Cedric F; Gorham, Edward D

    2017-04-01

    Fifteen nested case-control or cohort studies in 14 countries have examined the association between serum 25-hydroxyvitamin D [25(OH)D] and risk of colorectal cancer. A meta-analysis of these studies would provide a useful dose-response gradient curve based on pooling of the results of known studies to date. An up-to-date dose-response curve that combines the findings of these studies has not been reported, to our knowledge. This curve would help in designing interventions for future studies. A new meta-analysis would be more precise than any previous analysis due to its larger sample size. Therefore a search of PubMed and other resources was performed in May 2016 for all cohort or nested case-control observational studies that reported risk of colon or colorectal cancer by quantiles of 25(OH)D. All but two of the 15 studies found a trend toward lower risk of colorectal cancer associated with higher serum 25(OH)D. There was a linear reduction in the odds ratio (OR) with each 10ng/ml-increment in 25(OH)D concentration. The lowest quantile of the serum 25(OH)D concentration was generally<20ng/ml. The downward trend in ORs associated with higher serum 25(OH)D concentrations was statistically significant in 3 studies. The pooled OR from all studies comparing highest with lowest quantile of 25(OH)D was 0.67 (95% confidence interval [CI], 0.59-0.76), meaning there was a 33% lower risk associated with the highest compared with the lowest quantile of serum 25(OH)D. A dose-response analysis revealed that a serum 25(OH)D of 50ng/ml was associated with an OR of 0.4 (95% CI, 0.2-1.0) compared with a concentration of 5ng/ml. The formula for the linear relationship was OR=0.008x. For example, individuals with a 25(OH)D concentration of 50ng/ml had an approximately 60% lower risk of colorectal cancer than those with a concentration of 5ng/ml. Those with a 25(OH)D concentration of 30ng/ml had a 33% lower risk than those with a concentration of 5ng/ml. The inverse association

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

    PubMed Central

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

    2016-01-01

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

  20. Association of MHTFR Ala222Val (rs1801133) polymorphism and breast cancer susceptibility: An update meta-analysis based on 51 research studies

    PubMed Central

    2012-01-01

    Background The association between MHTFR Ala222Val polymorphism and breast cancer (BC) risk are inconclusive. To derive a more precise estimation of the relationship, a systematic review and meta-analysis was performed. Methods A comprehensive search was conducted through researching MEDLINE, EMBASE, PubMed, Web of Science, Chinese Biomedical Literature database (CBM) and China National Knowledge Infrastructure (CNKI) databases before August 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association. Results A total of 51 studies including 20,907 cases and 23,905 controls were involved in this meta-analysis. Overall, significant associations were found between MTHFR Ala222Val polymorphism and BC risk when all studies pooled into the meta-analysis (Ala/Ala vs Val/Val: OR=0.870, 95%CI=0.789–0.958,P=0.005; Ala/Val vs Val/Val: OR=0.895, 95%CI=0.821–0.976, P=0.012; dominant model: OR=0.882, 95%CI=0.808–0.963, P=0.005; and recessive model: OR = 0.944, 95%CI=0.898–0.993, P=0.026; Ala allele vs Val allele: OR = 0.935, 95%CI=0.887–0.986, P=0.013). In the subgroup analysis by ethnicity, the same results were found in Asian populations, while no significant associations were found for all comparison models in other Ethnicity populations. Conclusion In conclusion, our meta-analysis provides the evidence that MTHFR Ala222Val gene polymorphisms contributed to the breast cancer development. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1966146911851976 PMID:23217001

  1. Lack of Association between the CDH1 -160C>A Polymorphism and Risk of Gastrointestinal Cancer - a Meta-Analysis.

    PubMed

    Sahami-Fard, Mohammad Hossein; Yazd, Ehsan Farashahi; Khazaei, Zahra; Neamatzadeh, Hossein

    2016-01-01

    E-cadherin (CDH1) genetic variations alter gene transcriptional activity of epithelial cells in vitro and may cause susceptibility to various cancers. Associations of CDH1 -160C>A polymorphism with various cancers have been widely reported. However, the results are controversial and inconsistent. To derive a more accurate estimation of the relationship, a meta-analysis was performed with regard to gastrointestinal (GI) cancer risk. Eligible studies were identified through a search of PubMed database until December 2015. Associations between the CDH1 -160C>A polymorphism and GI cancer risk was considered by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 31 studies including 11,606 cases and 12,655 controls were involved in this meta-analysis. Overall, this meta-analysis showed no association between CDH1 -160C>A polymorphism and GI cancer risk (A vs. C: OR = 1.08, 95%CI = 0.98-1.18, P = 0.086;CA vs. CC: OR = 1.09, 95%CI = 0.97- 1.22, P = 0.118; AA vs. CC: OR = 1.10, 95%CI = 0.89-1.35, P = 0.356; AA vs. CC + CA: OR = 1.06, 95%CI = 0.96-1.18, P = 0.207; CA+AA vs. CC: OR = 1.01, 95%CI = 0.84-1.22, P = 0.89). In subgroup analysis, similar results were found. In conclusion, this meta-analysis has demonstrated that there is a lack of association of the CDH1-160C>A polymorphism with GI cancer susceptibility.

  2. The association of TNF-308 (G/A) gene polymorphisms and hepatocellular carcinoma risk: a meta-analysis

    PubMed Central

    Sun, Qing; Guo, Xuedan; Wang, Qi; Zhao, Fan

    2016-01-01

    Objective Many studies have examined the association between the TNF-308 G/A polymorphism gene polymorphisms and hepatocellular carcinoma risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. Methods The PubMed and CNKI (China National Knowledge Infrastructure) database was searched for case-control studies. Odds ratios (OR) with 95% CIs were used to determine the strength of association between the TNF-308 G/A polymorphisms and HCC risk. The pooled ORs for the risk associated with the TNF-308 G/A genotype, the A carriers (A/G + A/A) vs. the wild-type homozygotes (G/G), A/A vs. G/G were calculated, respectively. Subgroup analyses were done by ethnicity and smoking status. Heterogeneity assumptions were assessed by chi-square-based Q-test. Results Ultimately, 21 studies, comprising 2,923 hepatocellular carcinoma cases and 4,323 controls were included. Overall, the A carriers (G/A + A/A) vs. the wild-type homozygotes (G/G), the pooled OR was 1.05 (95% CI, 0.93-1.19; P=0.000 for heterogeneity), for A/A vs. G/G the pooled OR was 1.07 (95% CI, 0.95-1.21; P=0.007 for heterogeneity). In the stratified analysis by ethnicity, the significantly risks were found among non-Asians. However, for Asians, significantly risks were not found. Conclusions The TNF-308 G/A polymorphisms are not associated with hepatocellular carcinoma risk among Asians, but for non-Asians. PMID:27877013

  3. Genetic associations of the thyroid stimulating hormone receptor gene with Graves diseases and Graves ophthalmopathy: A meta-analysis

    PubMed Central

    Xiong, Haibo; Wu, Mingxing; Yi, Hong; Wang, Xiuqing; Wang, Qian; Nadirshina, Sophia; Zhou, Xiyuan; Liu, Xueqin

    2016-01-01

    Graves’ disease (GD) is a common thyroid disease, and Graves ophthalmopathy(GO) is the most common extra-thyroidal manifestation of GD. Genetic associations of the thyroid stimulating hormone receptor (TSHR) gene with GD and GO have been studied in different population groups for a long time. We aimed to obtain a more precise estimation of the effects of TSHR single nucleotide polymorphisms (SNPs) on GD/GO using a meta-analysis. Publications were searched on Pub Med and EMBASE up to December 30, 2015. Eight studies involving three SNPs (rs179247, rs12101255, and rs2268458), which included 4790 cases and 5350 controls, met the selection criteria. The pooled odds ratios (OR) and the 95% confidence intervals (CI) were estimated. SNPs rs179247 (dominant model [GG + GA vs. AA]: OR = 0.66, 95%CI: 0.61–0.73, P = 0.000, I2 = 0%) and rs12101255 (dominant model [TT + TC vs. CC]: OR = 1.67, 95%CI: 1.53–1.83, P = 0.000, I2 = 0%) were significantly associated with GD in all of the genetic models. TSHR rs12101255 and rs2268458 polymorphisms had no association between GO and GD (GD without GO). The results indicate that rs179247 and rs12101255 are likely to be genetic biomarkers for GD. Further studies with different population groups and larger sample sizes are needed to confirm the genetic associations of the TSHR gene with GD/GO. PMID:27456991

  4. Associations of non-symbolic and symbolic numerical magnitude processing with mathematical competence: a meta-analysis.

    PubMed

    Schneider, Michael; Beeres, Kassandra; Coban, Leyla; Merz, Simon; Susan Schmidt, S; Stricker, Johannes; De Smedt, Bert

    2016-01-14

    Many studies have investigated the association between numerical magnitude processing skills, as assessed by the numerical magnitude comparison task, and broader mathematical competence, e.g. counting, arithmetic, or algebra. Most correlations were positive but varied considerably in their strengths. It remains unclear whether and to what extent the strength of these associations differs systematically between non-symbolic and symbolic magnitude comparison tasks and whether age, magnitude comparison measures or mathematical competence measures are additional moderators. We investigated these questions by means of a meta-analysis. The literature search yielded 45 articles reporting 284 effect sizes found with 17,201 participants. Effect sizes were combined by means of a two-level random-effects regression model. The effect size was significantly higher for the symbolic (r = .302, 95% CI [.243, .361]) than for the non-symbolic (r = .241, 95% CI [.198, .284]) magnitude comparison task and decreased very slightly with age. The correlation was higher for solution rates and Weber fractions than for alternative measures of comparison proficiency. It was higher for mathematical competencies that rely more heavily on the processing of magnitudes (i.e. mental arithmetic and early mathematical abilities) than for others. The results support the view that magnitude processing is reliably associated with mathematic