Science.gov

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. Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

    PubMed

    Lindgren, Cecilia M; Heid, Iris M; Randall, Joshua C; Lamina, Claudia; Steinthorsdottir, Valgerdur; 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; Hugh Watkins; 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, Mark I

    2009-06-01

    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 = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-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.

  3. 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.

  4. 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

  5. A note on generalized Genome Scan Meta-Analysis statistics.

    PubMed

    Koziol, James A; Feng, Anne C

    2005-02-17

    Wise et al. introduced a rank-based statistical technique for meta-analysis of genome scans, the Genome Scan Meta-Analysis (GSMA) method. Levinson et al. recently described two generalizations of the GSMA statistic: (i) a weighted version of the GSMA statistic, so that different studies could be ascribed different weights for analysis; and (ii) an order statistic approach, reflecting the fact that a GSMA statistic can be computed for each chromosomal region or bin width across the various genome scan studies. We provide an Edgeworth approximation to the null distribution of the weighted GSMA statistic, and, we examine the limiting distribution of the GSMA statistics under the order statistic formulation, and quantify the relevance of the pairwise correlations of the GSMA statistics across different bins on this limiting distribution. We also remark on aggregate criteria and multiple testing for determining significance of GSMA results. Theoretical considerations detailed herein can lead to clarification and simplification of testing criteria for generalizations of the GSMA statistic.

  6. 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

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

    PubMed Central

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

    2011-01-01

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

  8. 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.

  9. Association of blepharitis with Demodex: a meta-analysis.

    PubMed

    Zhao, Ya-E; Wu, Li-Ping; Hu, Li; Xu, Ji-Ru

    2012-04-01

    To conduct a meta-analysis to confirm the association between Demodex infestation and blepharitis. We conducted a comprehensive and quantitative analysis of relevant published case-control studies which were found from the ISI Web of Knowledge, MEDLINE and CNKI from January 1950 to December 2010. Meta-analysis was applied for 13 of these and included matched data sets, using odds ratio (OR) as the effect indicator. Sensitivity was assessed. Eleven articles (13 matched data sets) covering four different countries and reporting 4741 participants (2098 blepharitis and 2643 controls) were eligible. The pooled OR in random effect models was 4.89 (95% confidence interval, 3.00-7.97). Sensitivity analysis showed that results of pooled ORs in different effect models, language, sample size, and control groups were completely consistent, which demonstrated a stable association between Demodex infestation and blepharitis by meta-analysis. The association between Demodex infestation and blepharitis was statistically significant. The conclusion implies that when conventional treatments for blepharitis fail, examination of Demodex mites and acaricidal therapy should be considered.

  10. Association of Raynaud's syndrome with interferons. A meta-analysis.

    PubMed

    Mohokum, M; Hartmann, P; Schlattmann, P

    2012-10-01

    Vasospastic disorders of the digital circulation such as the Raynaud's syndrome (RS) are known side-effects of treatment of interferons. The prevalence of RS in patients during treatment with interferons agents is not well-defined. The objective of this paper was to assess the prevalence of RS in patients receiving interferons - 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 patients receiving interferons. The studies provided sufficient data to estimate the prevalence of RS in patients receiving interferons. 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. Six eligible studies, contributing data on 183 subjects, were included in this meta-analysis. For RS in patients receiving interferons a pooled prevalence of 13.6% and 95% CI (95% CI 0.026, 0.313) was obtained. A mixture model analysis found three latent classes. Statistically, publication bias was not present (p-value 0.335). Despite some heterogeneity there is a possible indication of an association between RS and patients receiving interferons.

  11. Genetic associations in diabetic nephropathy: a meta-analysis.

    PubMed

    Mooyaart, A L; Valk, E J J; van Es, L A; Bruijn, J A; de Heer, E; Freedman, B I; Dekkers, O M; Baelde, H J

    2011-03-01

    This meta-analysis assessed the pooled effect of each genetic variant reproducibly associated with diabetic nephropathy. PubMed, EMBASE and Web of Science were searched for articles assessing the association between genes and diabetic nephropathy. All genetic variants statistically associated with diabetic nephropathy in an initial study, then independently reproduced in at least one additional study, were selected. Subsequently, all studies assessing these variants were included. The association between these variants and diabetic nephropathy (defined as macroalbuminuria/proteinuria or end-stage renal disease [ESRD]) was calculated at the allele level and the main measure of effect was a pooled odds ratio. Pre-specified subgroup analyses were performed, stratifying for type 1/type 2 diabetes mellitus, proteinuria/ESRD and ethnic group. The literature search yielded 3,455 citations, of which 671 were genetic association studies investigating diabetic nephropathy. We identified 34 replicated genetic variants. Of these, 21 remained significantly associated with diabetic nephropathy in a random-effects meta-analysis. These variants were in or near the following genes: ACE, AKR1B1 (two variants), APOC1, APOE, EPO, NOS3 (two variants), HSPG2, VEGFA, FRMD3 (two variants), CARS (two variants), UNC13B, CPVL and CHN2, and GREM1, plus four variants not near genes. The odds ratios of associated genetic variants ranged from 0.48 to 1.70. Additional variants were detected in subgroup analyses: ELMO1 (Asians), CCR5 (Asians) and CNDP1 (type 2 diabetes). This meta-analysis found 24 genetic variants associated with diabetic nephropathy. The relative contribution and relevance of the identified genes in the pathogenesis of diabetic nephropathy should be the focus of future studies.

  12. 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

  13. Meta-Analysis of Genome-Wide Linkage Scans of Attention Deficit Hyperactivity Disorder

    PubMed Central

    Zhou, Kaixin; Dempfle, Astrid; Arcos-Burgos, Mauricio; Bakker, Steven C.; Banaschewski, Tobias; Biederman, Joseph; Buitelaar, Jan; Castellanos, F.Xavier; Doyle, Alysa; Ebstein, Richard P.; Ekholm, Jenny; Forabosco, Paola; Franke, Barbara; Freitag, Christine; Friedel, Susann; Gill, Michael; Hebebrand, Johannes; Hinney, Anke; Jacob, Christian; Lesch, Klaus Peter; Loo, Sandra K.; Lopera, Francisco; McCracken, James T.; McGough, James J.; Meyer, Jobst; Mick, Eric; Miranda, Ana; Muenke, Maximilian; Mulas, Fernando; Nelson, Stanley F.; Nguyen, T.Trang; Oades, Robert D.; Ogdie, Matthew N.; Palacio, Juan David; Pineda, David; Reif, Andreas; Renner, Tobias J.; Roeyers, Herbert; Romanos, Marcel; Rothenberger, Aribert; Schäfer, Helmut; Sergeant, Joseph; Sinke, Richard J.; Smalley, Susan L.; Sonuga-Barke, Edmund; Steinhausen, Hans-Christoph; van der Meulen, Emma; Walitza, Susanne; Warnke, Andreas; Lewis, Cathryn M; Faraone, Stephen V.; Asherson, Philip

    2010-01-01

    Genetic contribution to the development of attention deficit hyperactivity disorder (ADHD) is well established. Seven independent genome-wide linkage scans have been performed to map loci that increase the risk for ADHD. Although significant linkage signals were identified in some of the studies, there has been limited replications between the various independent datasets. The current study gathered the results from all seven of the ADHD linkage scans and performed a Genome Scan Meta Analysis (GSMA) to identify the genomic region with most consistent linkage evidence across the studies. Genome-wide significant linkage (PSR=0.00034, POR=0.04) was identified on chromosome 16 between 64 and 83 Mb. In addition there are nine other genomic regions from the GSMA showing nominal or suggestive evidence of linkage. All these linkage results may be informative and focus the search for novel ADHD susceptibility genes. PMID:18988193

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

    PubMed Central

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

    2015-01-01

    Studies on the association between arsenic exposure and diabetes mellitus (DM) yielded inconsistent results. Epidemiologic data on the associations between arsenic exposures via inhalation and DM are limited. Therefore, we conducted a meta-analysis to evaluate the risk of DM associated with arsenic exposure. We searched the related literature through a systematic approach and analyzed the data according to the exposure route (inhalation and ingestion). We used random-effect models to estimate the summary relative risks (RRs) for DM associated with arsenic exposure and used I 2 statistics to assess the heterogeneity of studies. We identified 38 relevant studies, of which the 32 on the ingestion route showed a significant association between arsenic exposure and DM (RR = 1.57; 95% CI 1.27–1.93). Focusing on the 24 studies in which the diagnosis of DM was confirmed using laboratory tests or medical records, we found that the summary RR was 1.71 (95% CI 1.32–2.23), very close to the overall estimates. We concluded that ingested arsenic is associated with the development of DM, but the heterogeneity among the studies may affect the results. PMID:26000288

  15. The Association Between Anxiety and Falls: A Meta-Analysis.

    PubMed

    Hallford, David John; Nicholson, Geoff; Sanders, Kerrie; McCabe, Marita P

    2017-09-01

    Falls occur frequently among older adults and can lead to a range of adverse and debilitating outcomes. Although symptoms of clinical anxiety have been implicated as risk factors for falls, there is no current consensus on the empirical association between anxiety and falls. The current study aimed to address this gap in the literature by conducting a quantitative, meta-analytic review of findings from previous studies. A systematic literature search of bibliographic databases was conducted, yielding 18 studies that fit the criteria for inclusion in the meta-analysis. A random-effects model of all 18 studies showed a significant overall odds ratio of 1.53 (95% CI 1.28-1.83, p < .001), indicating that elevated levels of anxiety were associated with a 53% increased likelihood of falls. A high amount of variance among effect sizes was observed. Only age was identified as a moderator of this relationship in a subgroup of the samples. Clinical anxiety is associated with falls, however, further research is required to elucidate the factors that might moderate or mediate this relationship, the casual pathways through which they are related, and the associations between different types of anxiety and falls.

  16. 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

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

    PubMed Central

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

    2010-01-01

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

  18. 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. © 2016 The Foundation for the Scandinavian Journal of Immunology.

  19. 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.

  20. [Association between neutrophil-lymphocyte ratio and isolated coronary artery ectasia: a meta-analysis].

    PubMed

    Zhang, H; Chen, X

    2016-03-01

    To evaluate the association between neutrophil-lymphocyte ratio (NLR) and isolated coronary artery ectasia by meta-analysis. Case-control studies focusing the association between NLR and isolated coronary artery ectasia published before July 2015 were identified from PubMed, CBM, CNKI, WanFang, and VIP databases and references of related studies were also searched manually. After document screening, data extraction and quality evaluation, meta-analysis was performed using RevMan 5.3 software. Five case-control studies including 817 patients were identified. The result of meta-analysis showed the NLR level in the isolated coronary artery ectasia group was significantly higher than that of the control group (MD=0.89, 95%CI 0.07-1.00, P<0.01), and the loss of safety coefficient was 335 showing that the result of meta-analysis was reliable. Results from the present meta-analysis show that elevated NLR level may be associated with the presence of isolated coronary artery ectasia. However, further studies are warranted to establish the causal association between NLR level and presence of isolated coronary artery ectasia.

  1. Meta-analysis of gene-level tests for rare variant association.

    PubMed

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

    2014-02-01

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

  2. Association between BANK1 polymorphisms and susceptibility to autoimmune diseases: A meta-analysis.

    PubMed

    Bae, S-C; Lee, Y H

    2017-03-31

    This study aimed to explore whether BANK1 polymorphisms are associated with susceptibility to autoimmune diseases. We conducted a meta-analysis on the associations between the BANK1 rs10516487, rs3733197, and rs17266594 polymorphisms and autoimmune diseases. Twenty-two articles with a total of 22,684 patients and 36,437 controls were included in the meta-analysis. Meta-analysis revealed a significant association between autoimmune diseases and the BANK1 rs10516487 T allele (OR = 1.161, 95% CI = 1.092-1.275, p = 1.9 × 10-6, heterogeneity p<0.001). The analysis also revealed an association between autoimmune diseases and the BANK1 rs3733197 A allele (OR = 1.178, 95% CI = 1.105-1.256, p = 4.5 × 10-7, heterogeneity p = 0.002) and the rs17266594 T allele (OR = 1.189, 95% CI = 1.073-1.315, p = 0.001, heterogeneity p<0.001). Meta-analysis by autoimmune disease type revealed an association between both systemic lupus erythematosus and systemic sclerosis and the BANK1 rs10516487 T allele (OR = 1.294, 95% CI = 1.232-1.360, p<1.0 × 10-8, heterogeneity p = 0.556; OR = 1.102, 95% CI = 1.027-1.183, p = 0.017, heterogeneity p = 0.048). However, meta-analysis failed to indicate an association between the BANK1 rs10516487 T allele and rheumatoid arthritis (RA; OR = 1.006, 95% CI = 1.956-1.058, p = 0.819). This meta-analysis demonstrates that BANK1 rs10516487, rs3733197, and rs17266594 polymorphisms are associated with susceptibility to autoimmune diseases.

  3. 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

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

    PubMed

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

    2017-03-01

    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. 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. 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. 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.

  5. The association of folate and depression: A meta-analysis.

    PubMed

    Bender, Ansley; Hagan, Kelsey E; Kingston, Neal

    2017-07-22

    Previous research suggested that folate levels play an important role in the etiology and course of depression. However, the literature has been inconsistent with regard to differences in folate level between individuals with and without depression. The present meta-analysis synthesized the results of previous studies to examine whether individuals with depression had lower levels of folate than individuals without depression. Meta-analytic procedures were conducted in accordance with PRISMA guidelines. Studies evaluating folate levels in individuals with and without depression via red blood cell folate, serum folate, or dietary intake of folate methods were identified via PsycINFO and PubMed. Random-effects meta-analysis was conducted using Hedge's g, and moderation analysis was used for both folate measurement method and population type. Study heterogeneity was assessed with I(2) and publication bias was qualitatively assessed via funnel plot and quantitatively assessed with the trim-and-fill method and Begg's adjusted rank test. We found a significant, small effect size, such that individuals with depression had lower folate levels than those without depression, Hedge's g = -0.24 (95% CI = -0.31, -0.16), p < 0.001. Study heterogeneity was high (I(2) = 84.88%), and neither folate measurement method nor population accounted for study heterogeneity. Individuals with depression have lower serum levels of folate and dietary folate intake than individuals without depression. Given that previous literature suggested folate supplementation improved the efficacy of traditional antidepressant medications, future research on folate supplementation in depression is warranted and clinicians may wish to consider folate supplementation for patients with depression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. 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.

  7. Meta-Analysis of Associations Between Interleukin-10 Polymorphisms and Susceptibility to Vasculitis.

    PubMed

    Jung, Jae Hyun; Song, Gwan Gyu; Lee, Young Ho

    2015-01-01

    This study determined whether interleukin-10 (IL-10) polymorphisms are associated with susceptibility to vasculitis. A meta-analysis was conducted of the associations between the IL-10 -1082 G/A, -819 C/T, and -592 C/A polymorphisms and the haplotype of the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and vasculitis. A total of 21 comparative studies involving 4121 patients and 5504 controls were considered in the meta-analysis. Meta-analysis revealed no association between the IL-10-1082 G allele and vasculitis in all study subjects (OR = 0.927, 95% CI = 0.780-1.102, p = 0.389). However, disease-specific meta-analysis showed an association between Wegener's granulomatosis (WG) and the IL-10-1082 G allele (OR = 0.729, 95% CI = 0.547-0.971, p = 0.031). Meta-analysis revealed an association between vasculitis and the IL-10-819 C allele (OR = 0.804, 95% CI = 0.706-0.916, p = 0.001) in all study subjects and Behcet's disease (BD) (OR = 0.724, 95% CI = 0.679-0.781, p < 1.0 × 10(-9)). Meta-analysis of the IL-10-592 C allele showed an association with vasculitis in all study subjects (OR = 0.805, 95% CI = 0.619-0.938, p = 0.005) and BD (OR = 0.718, 95% CI = 0.661-0.781, p < 1.0 × 10(-9)). Meta-analysis of the IL-10 haplotype revealed an association between the GCC haplotype and vasculitis in Europeans (OR = 1.239, 95% CI = 1.105-1.513, p = 0.035). This meta-analysis showed that IL-10 polymorphisms are associated with vasculitis susceptibility, especially in WG and BD.

  8. General Framework for Meta-analysis of Rare Variants in Sequencing Association Studies

    PubMed Central

    Lee, Seunggeun; Teslovich, Tanya M.; Boehnke, Michael; Lin, Xihong

    2013-01-01

    We propose a general statistical framework for meta-analysis of gene- or region-based multimarker rare variant association tests in sequencing association studies. In genome-wide association studies, single-marker meta-analysis has been widely used to increase statistical power by combining results via regression coefficients and standard errors from different studies. In analysis of rare variants in sequencing studies, region-based multimarker tests are often used to increase power. We propose meta-analysis methods for commonly used gene- or region-based rare variants tests, such as burden tests and variance component tests. Because estimation of regression coefficients of individual rare variants is often unstable or not feasible, the proposed method avoids this difficulty by calculating score statistics instead that only require fitting the null model for each study and then aggregating these score statistics across studies. Our proposed meta-analysis rare variant association tests are conducted based on study-specific summary statistics, specifically score statistics for each variant and between-variant covariance-type (linkage disequilibrium) relationship statistics for each gene or region. The proposed methods are able to incorporate different levels of heterogeneity of genetic effects across studies and are applicable to meta-analysis of multiple ancestry groups. We show that the proposed methods are essentially as powerful as joint analysis by directly pooling individual level genotype data. We conduct extensive simulations to evaluate the performance of our methods by varying levels of heterogeneity across studies, and we apply the proposed methods to meta-analysis of rare variant effects in a multicohort study of the genetics of blood lipid levels. PMID:23768515

  9. Association between depression and periodontitis: a systematic review and meta-analysis.

    PubMed

    Araújo, Milena Moreira; Martins, Carolina Castro; Costa, Lidiane Cristina Machado; Cota, Luís Otávio Miranda; Faria, Rodrigo Lamounier Araújo Melo; Cunha, Fabiano Araújo; Costa, Fernando Oliveira

    2016-03-01

    The aim of this systematic review and meta-analysis was to assess the scientific evidence on the association between depression and periodontitis. An electronic search was conducted in three databases until October 2015 (PROSPERO-CRD42014006451). Hand searches and grey literature were also included. Search retrieved 423 potentially studies. Two independent reviewers selected the studies, extracted data and assessed risk bias through a modified version of Newcastle-Ottawa scale. Meta-analysis was performed for the presence/absence of periodontitis (dichotomic). Summary effect measures and odds ratio (OR) 95% CI were calculated. After selecting the studies, 15 were included in the systematic review (eight cross-sectional, six case-control and one cohort study). Six studies reported that depression was associated with periodontitis, whereas nine studies did not. The majority of studies had low risk of bias by methodological quality assessment. Meta-analysis of seven cross-sectional studies showed no significant association between depression and periodontitis (OR = 1.03, 95% CI = 0.75-1.41). Findings from the present systematic review showed a great heterogeneity among the studies and the summary effect measure of the meta-analysis cannot affirm an association between depression and periodontitis. Future studies with different designs in distinct populations should be conducted to investigate this association. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. 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…

  11. 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.

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

    USDA-ARS?s Scientific Manuscript database

    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-...

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  16. 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…

  17. 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…

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

    PubMed

    Ouyang, Zhiguo; Wang, Zhaoyan; Jin, Jian

    2014-01-01

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

  19. 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…

  20. Association between FOXP3 polymorphisms and susceptibility to autoimmune diseases: A meta-analysis.

    PubMed

    Lee, Min-Gu; Bae, Sang-Cheol; Lee, Young Ho

    2015-01-01

    The aim of this study was to explore whether the FOXP3 -3279 A/C polymorphism and (GT)n microsatellite polymorphisms are associated with susceptibility to autoimmune diseases. A meta-analysis was conducted on the associations between the FOXP3 -3279 A/C polymorphism and (GT)15 and (GT)16 polymorphisms and autoimmune diseases. Twenty-two comparative studies with a total of 7962 patients and 7453 controls were included in the meta-analysis. Meta-analysis revealed an association between autoimmune disease and the FOXP3 -3279 AA + AC genotype (OR = 1.480, 95% CI = 1.263-1.614, p < 1.0 × 10(-9)), and stratification by ethnicity indicated a significant association between the FOXP3 -3279 AA + AC genotype and autoimmune diseases in Asians (OR = 1.416, 95% CI = 1.225-1.637, p = 2.5 × 10(-7)) and non-Caucasians (OR = 1.432, 95% CI = 1.245-1.647, p = 7.5 × 10(-8)). In addition, corrected p values for multiple testing remained significant. Meta-analysis revealed no association between autoimmune disease and the FOXP3 (GT)15 allele (OR = 1.051, 95% CI = 0.933-1.183, p = 0.413). Similarly, the FOXP3 (GT)16 allele showed no associations with autoimmune disease. This meta-analysis indicates that the FOXP3 -3279 A/C polymorphism is associated with susceptibility to autoimmune disease in Asians and non-Caucasians.

  1. 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.

  2. Association between serum folate level and cervical cancer: a meta-analysis.

    PubMed

    Zhou, Xinyue; Meng, Yuanguang

    2016-04-01

    The aim of this study was to evaluate the association between serum folate level and cervical cancer. PubMed, Medline, Springer, Elsevier Science Direct, Cochrane Library and Google scholar were searched for relevant trials. Rev.Man5.1 and Stata 11.0 software were applied for this meta-analysis. Odds Ratio (OR) and 95 % confidence intervals (95 % CI) were collected and calculated in a fixed-effects model or a random-effects model when appropriate. Subgroup analysis was performed by sample size, participant's geographical location and definition of deficient serum folate level. A total of 6 case-control studies including 2383 participants were included in the meta-analysis. The overall meta-analysis showed that there were significant differences between cases and controls, suggesting that deficient serum folate level was associated with the increased risk of cervical cancer. After stratification subgroup analysis, significant difference was also found in subgroup with sample size <500 as well as in Asian population, but not in subgroup with sample size ≥500, American populations as well as different definition of deficient serum folate level (<6.4 ng/ml or others). Based on our meta-analysis, deficiency of serum folate level was associated with the increased risk of cervical cancer among Asian populations.

  3. Multivariate meta-analysis for non-linear and other multi-parameter associations

    PubMed Central

    Gasparrini, A; Armstrong, B; Kenward, M G

    2012-01-01

    In this paper, we formalize the application of multivariate meta-analysis and meta-regression to synthesize estimates of multi-parameter associations obtained from different studies. This modelling approach extends the standard two-stage analysis used to combine results across different sub-groups or populations. The most straightforward application is for the meta-analysis of non-linear relationships, described for example by regression coefficients of splines or other functions, but the methodology easily generalizes to any setting where complex associations are described by multiple correlated parameters. The modelling framework of multivariate meta-analysis is implemented in the package mvmeta within the statistical environment R. As an illustrative example, we propose a two-stage analysis for investigating the non-linear exposure–response relationship between temperature and non-accidental mortality using time-series data from multiple cities. Multivariate meta-analysis represents a useful analytical tool for studying complex associations through a two-stage procedure. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22807043

  4. Systematic Review and Meta-Analysis: Is Pre-Injury Antiplatelet Therapy Associated with Traumatic Intracranial Hemorrhage?

    PubMed

    van den Brand, Crispijn L; Tolido, Tanya; Rambach, Anna H; Hunink, Myriam G M; Patka, Peter; Jellema, Korné

    2017-01-01

    The objective of this systematic review and meta-analysis is to evaluate whether the pre-injury use of antiplatelet therapy (APT) is associated with increased risk of traumatic intracranial hemorrhage (tICH) on CT scan. PubMed, Medline, Embase, Cochrane Central, reference lists, and national guidelines on traumatic brain injury were used as data sources. Eligible studies were cohort studies and case-control studies that assessed the relationship between APT and tICH. Studies without control group were not included. The primary outcome of interest was tICH on CT. Two reviewers independently selected studies, assessed methodological quality, and extracted outcome data. This search resulted in 10 eligible studies with 20,247 patients with head injury that were included in the meta-analysis. The use of APT in patients with head injury was associated with significant increased risk of tICH compared with control (odds ratio [OR] 1.87, 95% confidence interval [CI]1.27-2.74). There was significant heterogeneity in the studies (I(2) 84%), although almost all showed an association between APT use and tICH. This association could not be established for patients receiving aspirin monotherapy. When considering only patients with mild traumatic brain injury (mTBI), the OR is 2.72 (95% CI 1.92-3.85). The results were robust to sensitivity analysis on study quality. In summary, APT in patients with head injury is associated with increased risk of tICH; this association is most relevant in patients with mTBI. Whether this association is the result of a causal relationship and whether this relationship also exists for patients receiving aspirin monotherapy cannot be established with the current review and meta-analysis.

  5. 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

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

    PubMed Central

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

    2013-01-01

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

  7. Association between TYK2 polymorphisms and susceptibility to autoimmune rheumatic diseases: a meta-analysis.

    PubMed

    Lee, Y H; Bae, S-C

    2016-10-01

    This study aimed to explore whether TYK2 polymorphisms are associated with susceptibility to autoimmune rheumatic diseases. We conducted a meta-analysis on the association between TYK2 polymorphisms and autoimmune rheumatic diseases. Twelve studies with a total of 16,335 patients and 30,065 controls were included in the meta-analysis. Meta-analysis revealed an association between rheumatic diseases and the 2 allele of the TYK2 rs2304256 (OR = 0.885, 95% CI = 0.802-0.978, p = 0.016). Furthermore, stratification by ethnicity identified a significant association between this polymorphism and rheumatic diseases in Caucasians (OR = 0.822, 95% CI = 0.706-0.889, p = 9.5 × 10(-7)), but not in Asians (OR = 1.127, 95% CI = 0.835-1.522, p = 0.434). Meta-analysis by rheumatic disease type revealed a significant association between the 2 allele of the TYK2 rs2304256 and SLE in Caucasians (OR = 0.737, 95% CI = 0.673-0.808, p < 1.0 × 10(-8)) but not in Asians (OR = 1.211, 95% CI = 0.813-1.804, p = 0.347). Meta-analysis revealed that the rs12720356 polymorphism was associated with susceptibility to rheumatic diseases in Caucasians (OR = 0.812, 95% CI = 0.661-0.997, p = 0.046) but not in Asians. Interestingly, the rs280519 polymorphism was significantly associated with susceptibility to SLE both in Caucasians and Asians. However, no associations were found between the rs12720270, rs280500, rs280523 and rs8108236 polymorphisms and susceptibility to rheumatic diseases. This meta-analysis demonstrates that the TYK2 rs2304256 and rs12720356 polymorphisms are associated with susceptibility to rheumatic diseases, rs2304256 polymorphism is associated with SLE in Caucasians, and rs280519 polymorphism is associated with SLE in Caucasians and Asians. © The Author(s) 2016.

  8. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-08-01

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

  11. Associations of general parenting and parent-child relationship with pediatric obesity: a meta-analysis.

    PubMed

    Pinquart, Martin

    2014-05-01

    The objective of the meta-analysis is to integrate available results on associations of general parenting (not specific to feeding and activity promotion) and parent-child relations with child weight status, eating, and physical activity. Searching in electronic databases and cross-referencing identified 156 empirical studies. Random-effects meta-analysis was computed. A positive parent-child relationship and higher levels of parental responsiveness were associated with lower weight, healthier eating, and more physical activity of the child. Parental demandingness, overprotection, psychological control, inconsistency, and parenting styles showed associations with some of the assessed outcome variables. Most effect sizes were small and varied by study characteristics. The small effects do not support making general parenting styles, parental demandingness, responsiveness, and the quality of the parent-child relationship a main target of preventing and treating obesity. Reducing parental inconsistency may be a better target if available results are replicated in future studies.

  12. Cluster headache and the hypocretin receptor 2 reconsidered: a genetic association study and meta-analysis.

    PubMed

    Weller, Claudia M; Wilbrink, Leopoldine A; Houwing-Duistermaat, Jeanine J; Koelewijn, Stephany C; Vijfhuizen, Lisanne S; Haan, Joost; Ferrari, Michel D; Terwindt, Gisela M; van den Maagdenberg, Arn M J M; de Vries, Boukje

    2015-08-01

    Cluster headache is a severe neurological disorder with a complex genetic background. A missense single nucleotide polymorphism (rs2653349; p.Ile308Val) in the HCRTR2 gene that encodes the hypocretin receptor 2 is the only genetic factor that is reported to be associated with cluster headache in different studies. However, as there are conflicting results between studies, we re-evaluated its role in cluster headache. We performed a genetic association analysis for rs2653349 in our large Leiden University Cluster headache Analysis (LUCA) program study population. Systematic selection of the literature yielded three additional studies comprising five study populations, which were included in our meta-analysis. Data were extracted according to predefined criteria. A total of 575 cluster headache patients from our LUCA study and 874 controls were genotyped for HCRTR2 SNP rs2653349 but no significant association with cluster headache was found (odds ratio 0.91 (95% confidence intervals 0.75-1.10), p = 0.319). In contrast, the meta-analysis that included in total 1167 cluster headache cases and 1618 controls from the six study populations, which were part of four different studies, showed association of the single nucleotide polymorphism with cluster headache (random effect odds ratio 0.69 (95% confidence intervals 0.53-0.90), p = 0.006). The association became weaker, as the odds ratio increased to 0.80, when the meta-analysis was repeated without the initial single South European study with the largest effect size. Although we did not find evidence for association of rs2653349 in our LUCA study, which is the largest investigated study population thus far, our meta-analysis provides genetic evidence for a role of HCRTR2 in cluster headache. Regardless, we feel that the association should be interpreted with caution as meta-analyses with individual populations that have limited power have diminished validity. © International Headache Society 2014.

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

    PubMed

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

    2016-04-01

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

  14. Association of MSX1 and TGF-β1 genetic polymorphisms with hypodontia: meta-analysis.

    PubMed

    Zhang, W; Qu, H C; Zhang, Y

    2014-11-28

    We conducted a comprehensive meta-analysis of 4 case-control studies to explore the association between polymorphisms of Msh homeobox 1 (MSX1) and transforming growth factor-β1 (TGF-β1) genes and hypodontia. A total of 643 tooth agenesis cases and 733 healthy controls were included in this study. The meta-analysis results showed that the T allele and T carrier (CT + TT) of rs1095 in the MSX1 gene were positively associated with hypodontia susceptibility. However, the T allele and T carrier (TC + CC) of rs12532 and rs8670 showed no association with cancer susceptibility. In addition, there were no strong associations between the T allele and T carrier (CT + TT) of C509T and the A allele and A carrier (AG + AA) of G800A in the TGF-β1 gene polymorphisms between patients with tooth agenesis and healthy subjects. In conclusion, these meta-analysis results demonstrated that polymorphisms in the rs1095 region of the MSX1 gene may influence the transcriptional activity of this gene and are associated with hypodontia in humans. However, the association between the TGF-β1 gene and sporadic tooth agenesis is not well understood, and further studies are required to explore the correlation between the TGF-β1 gene and hypodontia.

  15. 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

  16. 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

  17. 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.

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

    PubMed

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

    2014-11-01

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

  19. Association between sleep duration and cancer risk: a meta-analysis of prospective cohort studies.

    PubMed

    Lu, Yan; Tian, Nong; Yin, Jie; Shi, Yuhua; Huang, Zhenping

    2013-01-01

    Sleep duration has been shown to play an important role in the development of cancer. However, the results have been inconsistent. A meta-analysis with prospective cohort studies was performed to clarify the association between short or long sleep duration and cancer risk. PubMed and Embase databases were searched for eligible publications. Pooled relative risk (RR) with 95% confidence interval (CI) was calculated using random- or fixed- model. A total of 10 prospective studies (8392 incident cases and 555678 participants) were included in the meta-analysis. Neither short nor long sleep duration was statistically associated with increased risk of cancer (short sleep duration: RR=1.05, 95%CI=0.90-1.24, p=0.523; long sleep duration: RR=0.92, 95%CI=0.76-1.12, p=0.415). In the subgroup by cancer type, long sleep duration was positively associated with colorectal cancer (RR=1.29, 95%CI=1.09-1.52, p=0.003). The present meta-analysis suggested that neither short nor long sleep duration was significantly associated with risk of cancer, although long sleep duration increased risk of with colorectal cancer. Large-scale well-design prospective studies are required to be conducted to further investigate the observed association.

  20. Association of programmed cell death 1 polymorphisms and systemic lupus erythematosus: a meta-analysis.

    PubMed

    Lee, Y H; Woo, J H; Choi, S J; Ji, J D; Song, G G

    2009-01-01

    Programmed cell death 1 (PDCD1 or PD1) polymorphisms have been inconsistently reported to be associated with systemic lupus erythematosus (SLE). The aim of this study was to explore whether the PDCD1 polymorphisms confer a susceptibility to SLE and lupus nephritis (LN). We conducted a meta-analysis on the association of PDCD1 polymorphisms with SLE in overall and specific ethnic populations. A total of 15 separate comparisons were included in this meta-analysis consisting of nine Europeans, two Latin Americans, two Africans, one Asian and one unknown participant. In subgroup analysis, the PD1.3A allele was significantly associated with SLE in Latin Americans (OR = 3.073, 95% CI = 1.416-6.461, P = 0.003), but not in patients of European and African decent. The PD1.3A allele was a risk factor for LN in European descendants (OR = 2.207, 95% CI = 1.488-3.467, P < 0.001). The PD1.5C allele was a risk factor for SLE in Europeans (OR = 1.297, 95% CI = 1.024-1.643, P = 0.031). In conclusion, this meta-analysis demonstrated an association of the PD1.3A allele with LN in European and SLE in Latin-American populations. Furthermore, the PD1.5C allele was associated with SLE susceptibility in Europeans.

  1. 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

  2. Association Between Periodontitis and Gestational Diabetes Mellitus: Systematic Review and Meta-Analysis.

    PubMed

    Esteves Lima, Rafael Paschoal; Cyrino, Renata Magalhães; de Carvalho Dutra, Bernardo; Oliveira da Silveira, Juliana; Martins, Carolina Castro; Miranda Cota, Luis Otávio; Costa, Fernando Oliveira

    2016-01-01

    To the best of the authors' knowledge, there is no systematic review of the potential association between periodontitis and gestational diabetes mellitus (GDM) in the current literature. The aim of the present systematic review and meta-analysis is to search for scientific evidence regarding the association between periodontitis and GDM. The present study was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and registered (CRD2014010728) with PROSPERO (International prospective register for systematic reviews, University of York, York, UK). A search was conducted in three electronic databases without restrictions regarding language or date of publication. From 190 studies selected, 15 underwent full-text analysis. Eight studies were eligible (five cross-sectional and three case-control studies), and seven were entered in the meta-analysis. Meta-analysis was performed with tests for sensitivity and statistical heterogeneity. Summary effect measures were calculated by odds ratio (OR) and 95% confidence interval (CI). There was a significant association between periodontitis and GDM in the meta-analyses of four cross-sectional studies (OR 1.67, 95% CI 1.20 to 2.32) and two case-control studies (OR 2.66, 95% CI 1.52 to 4.65). However, sensitivity tests for case-control studies showed a lack of consistency in data; when including one case-control study, the significance was null (meta-analysis of three case-control studies: OR 1.69, 95% CI 0.68 to 4.21). There was substantial clinical, methodologic, and statistical heterogeneity among the studies. The scientific evidence cannot affirm a positive association between periodontitis and GDM. Future studies with different designs in distinct populations should be conducted to investigate this association.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Association of T174M polymorphism of angiotensinogen gene with essential hypertension: A meta-analysis.

    PubMed

    Liao, Xiaoyang; Yang, Zhiyi; Peng, Daqing; Dai, Hua; Lei, Yi; Zhao, Qian; Han, Yanbing; Wang, Weiwen

    2014-09-01

    The association between T174M polymorphism of angiotensinogen gene and essential hypertension risk remains controversial. We herein performed a meta-analysis to achieve a reliable estimation of their relationship. All the studies published up to May 2013 on the association between T174M polymorphism and essential hypertension risk were identified by searching the electronic repositories PubMed, MEDLINE and EMBASE, Springer, Elsevier Science Direct, Cochrane Library and Google Scholar. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Ultimately, nine eligible studies, including 2188 essential hypertension cases and 2459 controls, were enrolled in this meta-analysis. No significant associations were found under the overall ORs for M-allele comparison (M vs. T, pooled OR 0.92, 95% CI 0.62-1.37), MM vs. TT (pooled OR 0.86, 95% CI 0.29-2.51), TM vs. TT n (pooled OR 0.91, 95% CI 0.63-1.32), recessive model (MM vs. TT+TM, pooled OR 0.89, 95% CI 0.35-2.30), dominant model (MM+TM vs. TT, pooled OR 0.91, 95% CI 0.60-1.38) between T174M polymorphism and risk for essential hypertension. This meta-analysis suggested that the T174M polymorphism of the angiotensinogen gene might not be associated with the susceptibility of essential hypertension in Asian or European populations.

  11. Meta-analysis of perceived stress and its association with incident coronary heart disease.

    PubMed

    Richardson, Safiya; Shaffer, Jonathan A; Falzon, Louise; Krupka, David; Davidson, Karina W; Edmondson, Donald

    2012-12-15

    Most studies examining potential associations between psychological factors and cardiovascular outcomes have focused on depression or anxiety. The effect of perceived stress on incident coronary heart disease (CHD) has yet to be reviewed systematically. We conducted a systematic review and meta-analysis of the association between perceived stress and incident CHD. Ovid, MEDLINE, and PsycINFO were searched as data sources. Prospective observational cohort studies were selected that measured self-reported perceived stress and assessed incident CHD at ≥6 months. We extracted study characteristics and estimates of the risk of incident CHD associated with high perceived stress versus low perceived stress. We identified 23 potentially relevant articles, of which 6 met our criteria (n = 118,696). Included studies measured perceived stress with validated measurements and nonvalidated simple self-report surveys. Incident CHD was defined as new diagnosis of, hospitalization for, or mortality secondary to CHD. Meta-analysis yielded an aggregate risk ratio of 1.27 (95% confidence interval 1.12 to 1.45) for the magnitude of the relation between high perceived stress and incident CHD. In conclusion, this meta-analysis suggests that high perceived stress is associated with a moderately increased risk of incident CHD. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Steep delay discounting and addictive behavior: a meta-analysis of continuous associations.

    PubMed

    Amlung, Michael; Vedelago, Lana; Acker, John; Balodis, Iris; MacKillop, James

    2017-01-01

    To synthesize continuous associations between delayed reward discounting (DRD) and both addiction severity and quantity-frequency (QF); to examine moderators of these relationships; and to investigate publication bias. Meta-analysis of published studies examining continuous associations between DRD and addictive behaviors. Published, peer-reviewed studies on addictive behaviors (alcohol, tobacco, cannabis, stimulants, opiates and gambling) were identified via PubMed, MEDLINE and PsycInfo. Studies were restricted to DRD measures of monetary gains. Random-effects meta-analysis was conducted using Pearson's r as the effect size. Publication bias was evaluated using fail-safe N, Begg-Mazumdar and Egger's tests, meta-regression of publication year and effect size and imputation of missing studies. The primary meta-analysis revealed a small magnitude effect size that was highly significant (r = 0.14, P < 10(-14) ). Significantly larger effect sizes were observed for studies examining severity compared with QF (P = 0.01), but not between the type of addictive behavior (P = 0.30) or DRD assessment (P = 0.90). Indices of publication bias suggested a modest impact of unpublished findings. Delayed reward discounting is associated robustly with continuous measures of addiction severity and quantity-frequency. This relation is generally robust across type of addictive behavior and delayed reward discounting assessment modality. © 2016 Society for the Study of Addiction.

  13. Association between developmental defects of enamel and dental caries: A systematic review and meta-analysis.

    PubMed

    Vargas-Ferreira, F; Salas, M M S; Nascimento, G G; Tarquinio, S B C; Faggion, C M; Peres, M A; Thomson, W M; Demarco, F F

    2015-06-01

    Dental caries is the main problem oral health and it is not well established in the literature if the enamel defects are a risk factor for its development. Studies have reported a potential association between developmental defects enamel (DDE) and dental caries occurrence. We investigated the association between DDE and caries in permanent dentition of children and teenagers. A systematic review was carried out using four databases (Pubmed, Web of Science, Embase, and Science Direct), which were searched from their earliest records until December 31, 2014. Population-based studies assessing differences in dental caries experience according to the presence of enamel defects (and their types) were included. PRISMA guidelines for reporting systematic reviews were followed. Meta-analysis was performed to assess the pooled effect, and meta-regression was carried out to identify heterogeneity sources. From the 2558 initially identified papers, nine studies fulfilled all inclusion criteria after checking the titles, abstracts, references, and complete reading. Seven of them were included in the meta-analysis with random model. A positive association between enamel defects and dental caries was identified; meta-analysis showed that individuals with DDE had higher pooled odds of having dental caries experience [OR 2.21 (95% CI 1.3; 3.54)]. Meta-regression analysis demonstrated that adjustment for sociodemographic factors, countries' socioeconomic status, and bias (quality of studies) explained the high heterogeneity observed. A higher chance of dental caries should be expected among individuals with enamel defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Association of psoriasis with stroke and myocardial infarction: meta-analysis of cohort studies.

    PubMed

    Xu, T; Zhang, Y-H

    2012-12-01

    Psoriasis is a common, chronic, relapsing, inflammatory skin disorder. Observational studies suggest an association between psoriasis and the incidence of stroke or myocardial infarction (MI). However, whether psoriasis is an independent risk factor for these two vascular events remains controversial. To evaluate the association of psoriasis with stroke and MI by conducting a meta-analysis of cohort studies. Cohort studies were searched in MEDLINE (Pubmed), EMBASE and Cochrane Library from their inception to March 2012. Stroke and MI were considered as a composite endpoint. Two authors independently extracted information on the characteristics of the study participants, follow-up range and control for potential confounding factors. A random-effects model was used to calculate the overall combined risk estimates. Seven cohort studies were included in the meta-analysis. On the basis of cohort characteristics, five of them were considered good quality and two were fair. The overall combined relative risk for psoriasis and composite vascular endpoint was 1·2 (95% confidence interval 1·1-1·31). Subgroup analysis maintained this significance with respect to stroke and MI individually. Sensitivity analysis and 'trim and fill' method yielded similar results. No evidence of publication bias was observed. This meta-analysis of cohort studies suggests that psoriasis significantly increases the risk of stroke and MI. The increase is probably independent of conventional cardiovascular risk factors. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

  15. Association of Helicobacter pylori with Chronic Kidney Diseases: A Meta-Analysis.

    PubMed

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

    2017-08-01

    The reported risk of chronic kidney disease (CKD) in patients with Helicobacter pylori infection is conflicting. This meta-analysis was conducted to summarize all available data and to estimate the prevalence and association between H. pylori and kidney disease and CKD. Comprehensive literature review was conducted using MEDLINE and EMBASE database through October 2016 to identify studies that reported the prevalence or the association between H. pylori infection and non-dialysis-dependent kidney diseases or CKD. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. Of 4546 studies, nine cross-sectional studies met the eligibility criteria and were included in the meta-analysis. The estimated prevalence of H. pylori infection among subjects with kidney disease was 53% (95% CI 45-61%). The pooled OR of H. pylori in patients with non-dialysis-dependent kidney diseases was 1.20 (95% CI 0.73-1.97) when compared with the patients without kidney diseases. The meta-analysis was then limited to only studies evaluating the risk of H. pylori in CKD; the pooled OR of H. pylori in patients with CKD was 1.00 (95% CI 0.58-1.71). The estimated prevalence of H. pylori in patients with non-dialysis-dependent kidney diseases is 53%. This study does not support the association between H. pylori infection and non-dialysis-dependent kidney diseases nor CKD.

  16. The association between physical activity and renal cancer: systematic review and meta-analysis

    PubMed Central

    Behrens, G; Leitzmann, M F

    2013-01-01

    Background: Physical activity may decrease renal cancer risk by reducing obesity, blood pressure, insulin resistance, and lipid peroxidation. Despite plausible biologic mechanisms linking increased physical activity to decreased risk for renal cancer, few epidemiologic studies have been able to report a clear inverse association between physical activity and renal cancer, and no meta-analysis is available on the topic. Methods: We searched the literature using PubMed and Web of Knowledge to identify published non-ecologic epidemiologic studies quantifying the relationship between physical activity and renal cancer risk in individuals without a cancer history. Following the PRISMA guidelines, we conducted a systematic review and meta-analysis, including information from 19 studies based on a total of 2 327 322 subjects and 10 756 cases. The methodologic quality of the studies was examined using a comprehensive scoring system. Results: Comparing high vs low levels of physical activity, we observed an inverse association between physical activity and renal cancer risk (summary relative risk (RR) from random-effects meta-analysis=0.88; 95% confidence interval (CI)=0.79–0.97). Summarising risk estimates from high-quality studies strengthened the inverse association between physical activity and renal cancer risk (RR=0.78; 95% CI=0.66–0.92). Effect modification by adiposity, hypertension, type 2 diabetes, smoking, gender, or geographic region was not observed. Conclusion: Our comprehensive meta-analysis provides strong support for an inverse relation of physical activity to renal cancer risk. Future high-quality studies are required to discern which specific types, intensities, frequencies, and durations of physical activity are needed for renal cancer risk reduction. PMID:23412105

  17. 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

  18. Meta-analysis: Association of Helicobacter pylori infection with Parkinson's diseases.

    PubMed

    Shen, Xiaoli; Yang, Huazhen; Wu, Yili; Zhang, Dongfeng; Jiang, Hong

    2017-10-01

    The results from observational studies on the relationship between helicobacter pylori (H. pylori) infection and Parkinson's disease remain controversial. A meta-analysis was conducted to evaluate the association between helicobacter pylori infection and Parkinson's disease. A comprehensive literature search was performed on relevant studies published from January 1983 to January 2017 in PubMed, Web of Science and EMBASE databases. The fixed or random effects model was used to pool the odds ratio with 95% confidence interval from individual studies. Publication bias was estimated by Egger's test and the funnel plot. Eight eligible studies involving 33 125 participants were included in this meta-analysis. Compared with the no helicobacter pylori infected person, the pooled odds ratio of Parkinson's disease in helicobacter pylori infected person was 1.59 (95% confidence interval: 1.37-1.85). In subgroup analyzes, the combined odds ratios were 1.96 (1.23-3.12) in Asia, 1.55 (1.32-1.82) in Europe, 1.59 (1.35-1.88) in case-control studies, 1.56 (1.01-2.39) in cross-sectional studies, 1.56 (1.32-1.85) in studies with confounders adjusted, and 1.71 (1.21-2.43) in studies with no confounder adjusted, respectively. This meta-analysis indicated that H. pylori infection might be associated with the risk of Parkinson's disease. © 2017 John Wiley & Sons Ltd.

  19. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2012-12-01

    Systematic review and meta-analysis to investigate the association between maternal AGTR1 gene single nucleotide polymorphisms (SNPs) and preeclampsia (PE). A systematic literature search was performed using PubMed, EMBASE, Scopus, and HuGE Literature Finder databases. The review was conducted according to PRISMA guidelines. Summary odds ratios (ORs) for the allelic and genotypic contrasts were calculated and compared to indicate the most appropriate genetic model for the polymorphism of interest. Among-study heterogeneity was assessed using the I(2) statistic and publication bias was evaluated visually using funnel plots. Seven maternal SNPs investigated with PE were found, but only AGTR1 +1166A>C accumulated sufficient evidence for meta-analysis. Summary ORs calculated from eight studies (10 populations involving 845 PE cases and 1150 controls) did not reveal an association between the +1166A>C polymorphism and PE (allelic OR = 1.19, 95% CI: 0.96-1.47). No evidence of publication bias and among-study heterogeneity was detected. meta-analysis findings did not support AGTR1 +1166A>C as a susceptibility locus for PE. Other AGTR1 SNPs require more study.

  2. 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.

  3. Association between circadian preference and academic achievement: A systematic review and meta-analysis.

    PubMed

    Tonetti, Lorenzo; Natale, Vincenzo; Randler, Christoph

    2015-01-01

    The association between circadian preference and academic achievement has been assessed through a systematic review and meta-analysis. The literature searches retrieved 1647 studies; 31 studies, with a total sample size of 27 309 participants, fulfilled the inclusion criteria and were included in the meta-analysis. With reference to all these 31 studies, before running the meta-analysis, the sign of the correlation between the investigated variables was set in a way that a positive correlation showed that eveningness was related to worse academic performance. The meta-analysis yielded a small overall effect size of 0.143 (CI [0,129; 0,156]) under a fixed effects model (Z = 20.584, p < 0.001, I(2)( )= 72.656; Q = 109.715) and of 0.145 (CI [0.117; 0.172]) under a random effects model (Z = 10.077, p < 0.001). A random effects model with a grouping variable (participants) revealed 15 studies based on school pupils and 16 on university students. The random model showed a higher effect size in school pupils (0.166, CI from 0.127 to 0.206) compared to university students (0.121, CI from 0.080 to 0.163). Self-report measures of grades revealed a stronger effect size (0.171; CI: 0.137 to 0.206; N = 20) compared to objective measures (0.093; CI: 0.047 to 0.140; N = 19). Overall, the present results suggest that evening orientation is associated with a worse academic performance, both in school pupils and university students; for the first time, it has been shown that such relationship changes over time, being weaker in university students.

  4. 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

  5. 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.

  6. 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

  7. 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

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

    PubMed

    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

    2017-02-10

    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.

  9. Association of coffee drinking with all-cause mortality: a systematic review and meta-analysis.

    PubMed

    Zhao, Yimin; Wu, Kejian; Zheng, Jusheng; Zuo, Ruiting; Li, Duo

    2015-05-01

    We aimed to use the meta-analysis method to assess the relationship between coffee drinking and all-cause mortality. Categorical and dose-response meta-analyses were conducted using random-effects models. We systematically searched and identified eligible literature in the PubMed and Scopus databases. Seventeen studies including 1 054 571 participants and 131 212 death events from all causes were included in the present study. Seventeen studies were included and evaluated in the meta-analysis. A U-shaped dose-response relationship was found between coffee consumption and all-cause mortality (P for non-linearity <0.001). Compared with non/occasional coffee drinkers, the relative risks for all-cause mortality were 0.89 (95 % CI 0.85, 0.93) for 1-<3 cups/d, 0.87 (95 % CI 0.83, 0.91) for 3-<5 cups/d and 0.90 (95 % CI 0.87, 0.94) for ≥5 cups/d, and the relationship was more marked in females than in males. The present meta-analysis of prospective cohort studies indicated that light to moderate coffee intake is associated with a reduced risk of death from all causes, particularly in women.

  10. Complications associated with autologous rib cartilage use in rhinoplasty: a meta-analysis.

    PubMed

    Wee, Jee Hye; Park, Min-Hyun; Oh, Sohee; Jin, Hong-Ryul

    2015-01-01

    Although autologous rib cartilage is a preferred source of graft material in rhinoplasty, rib cartilage for dorsal augmentation has been continuously criticized for its tendency to warp and for high donor-site morbidities. However, no meta-analysis or systemic review on complications associated with autologous rib cartilage use in rhinoplasty has been conducted. To carry out a systematic review and a meta-analysis of available literature to evaluate complications regarding autologous rib cartilage in rhinoplasty. The studies reporting complications associated with the autologous rib cartilage use in rhinoplasty were systematically reviewed by searching the MEDLINE, PubMed, and Embase databases for sources published from 1946 through June 2013. The selected articles included clinical studies conducted with at least 10 patients and at least 1 postoperative long-term complication or donor-site morbidity in rhinoplasty. Excluded were nonhuman studies; review articles; case reports; abstracts; and reports of nasal reconstruction as indication for surgery, use of homologous rib cartilage, and diced or laminated methods. Two investigators independently reviewed all studies and extracted the data using a standardized form. A meta-analysis was performed using a random-effects model. Number of patients; follow-up duration; and rates of complication, donor-site morbidity, and revision surgery. Also noted were study authors and year of publication. Ten studies involving a total 491 patients were identified. Mean follow-up across all studies was 33.3 months. In meta-analysis, the combined rates were 3.08% (95% confidence interval [CI], 0%-10.15%) for warping, 0.22% (95% CI, 0%-1.25%) for resorption, 0.56% (95% CI, 0%-2.61%) for infection, 0.39% (95% CI, 0%-1.97%) for displacement, 5.45% (95% CI, 0.68%-13.24%) for hypertrophic chest scarring, 0% (95% CI, 0%-0.32%) for pneumothorax, and 14.07% (95% CI, 6.19%-24.20%) for revision surgery. The overall long-term complications and

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

    PubMed Central

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

    2011-01-01

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

  12. Association between depression and neuropathy in people with type 2 diabetes: a meta-analysis.

    PubMed

    Bartoli, Francesco; Carrà, Giuseppe; Crocamo, Cristina; Carretta, Daniele; La Tegola, Davide; Tabacchi, Tommaso; Gamba, Pierluigi; Clerici, Massimo

    2016-08-01

    Depression and neuropathy are frequent complications of type 2 diabetes. The current meta-analysis aimed to estimate the association between depression and neuropathy in subjects with type 2 diabetes. We systematically searched electronic databases for articles published up to February 2015, providing data on the association between depression and neuropathy in individuals with type 2 diabetes. No language restrictions were applied. The meta-analysis generated random-effect odds ratios with 95% confidence intervals (95% CI). Risk of publication bias and heterogeneity were estimated using the Egger test and I(2) index, respectively. Leave-one-out analysis was performed. Data were analysed using stata. Thirteen studies were included in the meta-analysis. Data on the association between depression and neuropathy were available for 3898 individuals with type 2 diabetes. Pooled analysis showed an association between depression and neuropathy, with an odds ratio of 2.01 (95% CI: 1.60-2.54; p < 0.001). There was no risk of publication bias (p = 0.064), and heterogeneity was moderate (I(2)  = 44.5%). Leave-one-out analysis confirmed consistency of the findings. The association appeared partly influenced by age, because studies selecting older people (sample mean age > 65 years) showed a slightly higher estimate for the association. We found an association between depression and neuropathy among people with type 2 diabetes. Because of the cross-sectional nature of included studies, the relationship between these two conditions might be bidirectional. Further research exploring factors that might moderate or mediate this association is needed. Targeted interventions for comorbid depression and neuropathy should be implemented in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  13. 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.

  14. 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

  15. Associations between TNFAIP3 gene polymorphisms and systemic lupus erythematosus: a meta-analysis.

    PubMed

    Lee, Young Ho; Song, Gwan Gyu

    2012-09-01

    The aim of this study was to determine whether the tumor necrosis factor-alpha-inducible protein 3 (TNFAIP3) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. The authors conducted meta-analyses on associations between the TNFAIP3 polymorphisms and SLE susceptibility, using fixed and random effects models. A total of eight comparative studies were included in this meta-analysis, which included four Asian, three European, and one African American population. Meta-analysis revealed that an association was found between the minor allele of rs2230926 and SLE in all subjects (odds ratio [OR] 1.848, 95% confidence interval [CI] 1.547-2.208, p<1.0×10(-9)). After stratification by ethnicity, the minor allele of rs2230926 was found to be significantly associated with SLE in Asians and Europeans (OR 1.821, 95% CI 1.495-2.219, p<1.0×10(-9); OR 2.251, 95% CI 1.830-2.768, p<1.0×10(-9)). In addition, a significant association was found between the minor allele of the rs5029939 polymorphism and the risk of developing SLE in all study subjects and Europeans (OR 1.804, 95% CI 1.255-2.592, p=0.001; OR 2.145, 95% CI 1.731-2.658, p<1.0×10(-9)). Furthermore, an association was found between the minor allele of rs3757173 and SLE in all study subjects (OR 1.540, 95% CI 1.017-2.331, p=0.041). However, no association was found between SLE susceptibility and rs6922466 (OR 0.953, 95% CI 0.812-1.120, p=0.561). This meta-analysis confirms that the TNFAIP3 polymorphisms are associated with SLE susceptibility in different ethnic groups, namely in Asians and Europeans.

  16. Associations between interleukin-1 polymorphisms and susceptibility to vasculitis: a meta-analysis.

    PubMed

    Song, G G; Kim, J-H; Lee, Y H

    2016-05-01

    The objective of this study was to determine whether interleukin-1 (IL-1) polymorphisms are associated with susceptibility to vasculitis. A meta-analysis was conducted to investigate possible associations between IL-1A, IL-1B, and IL-1 receptor antagonist (IL1RN) polymorphisms and vasculitis. A total of 17 studies involving 1384 vasculitis cases [Behçet's disease (BD), IgA vasculitis, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), Kawasaki disease (KD), giant cell arteritis, and Takayasu's arteritis] and 2710 controls were included in the meta-analysis. This analysis showed an association between BD and the TT + TC genotypes of the IL-1A-889 C/T polymorphism in the entire study population [odds ratio (OR) = 0.623, 95 % CI = 0.395-0.981, p = 0.045), and a trend toward an association in a Turkish population (OR = 0.578, 95 % CI = 0.331-1.010, p = 0.054). A meta-analysis of the IL1RN polymorphism revealed no association with vasculitis in all study subjects (OR for IL1RN*2 = 0.904, 95 % CI = 0.626-1.304, p = 0.588). However, stratification by ethnicity revealed a significant association between the IL1RN*2 allele and vasculitis including AAV, BD, KD in Asians (OR = 2.393, 95 % CI = 1.429-4.006, p = 0.001), but not in Caucasian and Turkish populations (OR = 0.776, 95 % CI = 0.487-1.238, p = 0.288; OR = 0.914, 95 % CI = 0.667-1.252, p = 0.576, respectively). No association was found between vasculitis and the IL-1B-511 C/T polymorphism, or the IL-1B+3953 C/T polymorphism. This meta-analysis suggests that the IL-1A-889 C/T polymorphism is associated with susceptibility to BD, and that the IL1RN*2 allele is associated with susceptibility to vasculitis including AAV, BD, and KD in Asians.

  17. 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.

  18. 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

  19. 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

  20. Association between MTHFR A1298C polymorphism and male infertility: A meta-analysis.

    PubMed

    Zhang, Qiang; Yin, Guo-Ying; Liu, Juan; Liang, Yue; Li, Yao-Yan; Zhao, Jing-Yu; Zhang, Li-Wen; Wang, Bai-Qi; Tang, Nai-Jun

    2017-04-01

    There have been several epidemiological studies evaluating the potential association between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the risk of male infertility. However, the results obtained were inconsistent. Therefore, we performed a meta-analysis to further examine the association between the MTHFR A1298C polymorphism and male infertility. A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to January 15th, 2016. A total of 20 studies with 4293 cases and 4507 controls were included. An odds ratio (OR) and a 95% confidence interval (95% CI) were calculated to assess the strength of the association. A cumulative meta-analysis, sensitivity analysis and assessment of the publication bias were also performed in this study. The results showed that in the overall analysis, the association between the MTHFR A1298C polymorphism and male infertility was not significant. A stratified analysis by ethnicity revealed a significant increase in the risk of male infertility in the Asian population with the MTHFR A1298C polymorphism (especially in the heterozygote model: OR=1.20, 95% CI=1.01-1.44, P=0.994; the dominant model: OR=1.23, 95% CI=1.04-1.45, P=0.996; and the allele model: OR=1.20, 95% CI=1.04-1.39, P=0.985) but not in the Caucasian population. In the stratified analyses, no significant association was observed between the different types of male infertility. This meta-analysis suggests the MTHFR A1298C polymorphism may be a potential risk factor for male infertility, especially in the Asian population.

  1. Association of VEGF gene polymorphisms with diabetic retinopathy: a meta-analysis.

    PubMed

    Gong, Jian-Yang; Sun, Ye-Huan

    2013-01-01

    Studies on the association of vascular endothelial growth factor (VEGF) gene -460T/C and -2578C/A polymorphisms with diabetic retinopathy (DR) have reported conflicting results. The aim of the present study was to assess the association by using meta-analysis. A systematic search of electronic databases (PubMed, EMBASE, Elsevier Science Direct, ISI Web of Science, CBM, CNKI and VIP) was carried out until Sept 18, 2013. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to assess the strength of the association. Eleven studies (-460T/C: 6 studies including 932 cases and 722 controls; -2578C/A: 6 studies including 1,071 cases and 1,137 controls) were involved in this meta-analysis. Significant association was found for -460T/C polymorphism (C versus T: OR=1.48, 95%CI=1.07-2.05, P=0.02; TC+CC versus TT: OR=1.78, 95%CI=1.02-3.12, P=0.04; CC versus TT+TC: OR=1.76, 95%CI=1.10-2.81, P=0.02), but not for -2578C/A polymorphism (P>0.05). Similar results were found in the subgroup analysis. This meta-analysis demonstrates that DR is associated with VEGF gene -460T/C polymorphism, but not -2578C/A polymorphism. Further case-control studies based on larger sample size are still needed, especially for -2578C/A polymorphism.

  2. 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 %).

  3. 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.

  4. 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.

  5. Association between PPAR-γ2 Pro12Ala polymorphism and obesity: a meta-analysis.

    PubMed

    Yao, Ying-Shui; Li, Jie; Jin, Yue-Long; Chen, Yan; He, Lian-Ping

    2015-06-01

    The peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) gene has been reported in the pathogeny of obesity. However, the results have been inconsistent. The purpose of this meta-analysis was to acquire a more accurate assessment of the association between PPAR-γ2 Pro12Ala polymorphism and obesity. PubMed, Wan Fang (Chinese) databases, Chinese Biomedical Medical databases, and Chinese National Knowledge Infrastructure were searched to identify eligible studies. Finally, 25 studies (6491 cases and 8242 controls) were enrolled in this meta-analysis. The effect summary odds ratio (OR) with 95 % confidence interval (CI) was applied. Random-effects or fixed-effects model was performed based on the heterogeneity. STATA 12.0 was applied for this meta-analysis. The combined results showed that PPAR-γ Pro12Ala polymorphism was associated with the obesity risk (Ala vs. Pro: OR = 1.55, 95 % CI 1.34-1.80; Pro/Ala vs. Pro/Pro: OR = 1.54, 95 % CI 1.31-1.82; Ala/Ala + Pro/Ala vs. Pro/Pro: OR = 1.61, 95 % CI 1.36-1.90). Subgroup analysis by ethnicity showed that there were significant associations between PPAR-γ Pro12Ala polymorphism and obesity risk in Caucasians, Asians, and Mixed population. Subgroup analysis by obesity's cutoff points showed that the associations were found among the patients with the cutoff point of BMI ≥24 and BMI ≥30 but not among the patients with the cutoff point of BMI ≥95th percentile. These results suggested that PPAR-γ Pro12Ala polymorphism might be a risk factor for obesity susceptibility.

  6. Nerve injuries associated with pediatric supracondylar humeral fractures: a meta-analysis.

    PubMed

    Babal, Jessica C; Mehlman, Charles T; Klein, Guy

    2010-01-01

    Supracondylar fractures of the humerus are the most common type of elbow fracture in children. Of all complications associated with supracondylar fractures, nerve injury ranks highest, although reports of the incidence of specific neurapraxia vary. This meta-analysis aims primarily to determine the risk of traumatic neurapraxia in extension-type supracondylar fractures as compared with that of flexion-type fractures; secondarily it aims to use subgroup analysis to assess the risk of iatrogenic neurapraxia induced by pin fixation. A literature search identified studies that reported the incidence of nerve injury presenting with displaced supracondylar fractures of the humerus in children. Meta-analysis was subsequently performed to evaluate the risk of traumatic neurapraxia associated with supracondylar fractures. Subgroup analysis of included articles was additionally performed to assess the risk of iatrogenic neurapraxia associated with lateral-only or medial/lateral pin fixation. Data from 5148 patients with 5154 fractures were pooled for meta-analysis. Among these patients, traumatic neurapraxia occurred at a weighted event rate of 11.3%. Anterior interosseous nerve injury predominated in extension-type fractures, representing 34.1% of associated neurapraxias; meanwhile, ulnar neuropathy occurred most frequently in flexion-type injuries, representing 91.3% of associated neurapraxias. Nerve injury induced by lateral-only pinning occurred at a weighted event rate of 3.4%, while the introduction of a medial pin elicited neurapraxia at a weighted event rate of 4.1%. Lateral pinning carried increased risk of median neuropathy, whereas the use of a medial pin significantly increased the risk of ulnar nerve injury. Of nerve injury associated with extension-type fractures, anterior interosseous neurapraxia ranks highest, whereas of flexion-type neuropathy, ulnar nerve injury predominates. We confirm that medial pinning carries the greater overall risk of nerve injury as

  7. 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.

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

    PubMed

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

    2014-03-01

    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.

  9. The association between maternal subclinical hypothyroidism and growth, development, and childhood intelligence: a meta-analysis.

    PubMed

    Liu, Yahong; Chen, Hui; Chen, Jing; Li, Fupin

    2017-09-29

    To explore the association between maternal subclinical hypothyroidism (SCH) in pregnancy and the development of their children. Using RevMan 5.3 software, we performed a meta-analysis of cohort studies published from inception to May 2017, focusing on the association between maternal SCH in pregnancy and childhood growth, development and intelligence. Sources included the Cochrane Library, Pub-Med, Web of Science, CNKI, and Wan Fang Data. We included a total of 15 cohort studies involving 1,896 pregnant women with SCH. SCH in pregnancy was significantly associated with child's intelligence (P = 0.0007) and motor development (P < 0.00001). SCH was significantly associated with the child's weight in four studies involving 222 women (P = 0.02). Maternal SCH in pregnancy was identified as a risk factor for fetal growth restriction with a combined RR value of 2.4 [95% CI: 1.56, 3.7]. Meta-analysis of 10 studies that provided numbers of preterm infants revealed a significant association between maternal SCH in pregnancy and premature delivery, with a combined RR of 1.96 (95% CI: 1.34, 2.88). There was a significant effect of maternal SCH in pregnancy on fetal distress in utero (P = 0.003). Maternal SCH in pregnancy is associated with increased risk of adverse neonatal outcomes, including delayed intellectual and motor development, low birth weight, premature delivery, fetal distress and fetal growth restriction. .

  10. Lack of association between p53 codon 72 polymorphism and endometrial cancer: a meta-analysis.

    PubMed

    Tang, Wenru; He, Xinggang; Chan, Ying; Luo, Ying

    2012-06-01

    It has been suggested that the p53 tumor suppressor gene Arg72Pro polymorphism is associated with endometrial cancer. However, results have been inconsistent. We performed this meta-analysis to estimate the association between p53 Arg72Pro polymorphism and endometrial cancer. An electronic search of PubMed was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and the association was assessed by pooled odds ratios (ORs) with 95% confidence intervals (CIs). Nine published studies, including 829 endometrial cancer cases and 1387 controls, were identified. The overall results suggested that the variant genotypes were not associated with the endometrial cancer risk in all genetic models (additive model: OR 1.027, 95% CI 0.893-1.18, P=0.71; recessive model: OR 1.099, 95% CI 0.802-1.507, P=0.556; dominant model: OR 1.013, 95% CI 0.842-1.219 P=0.89). Similarly, the results were negative in subgroup analyses for ethnicity (Caucasian, Asian). This meta-analysis suggests that p53 codon 72 polymorphism is not associated with increased risk of endometrial cancer, especially in Caucasians and Asians. To validate the association between this polymorphism and endometrial cancer, further studies with larger numbers of participants worldwide are needed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. 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

  12. Meta-analysis of the association between cysticercosis and epilepsy in Africa.

    PubMed

    Quet, Fabrice; Guerchet, Maëlenn; Pion, Sebastien D S; Ngoungou, Edgard B; Nicoletti, Alessandra; Preux, Pierre-Marie

    2010-05-01

    The association between cysticercosis and epilepsy has been widely studied in Latin America and Asia and has proven to be one of the main causes of epilepsy. Despite high prevalences of both diseases in Africa, their association remains unclear. In this article we quantified the strength of the association between epilepsy and cysticercosis in Africa and we proposed some guidelines for future studies. We performed a systematic review of literature on cysticercosis (considered as exposure) and epilepsy (considered as the disease) and collected data from both cross-sectional and case-control studies. A common odds ratio was estimated using a random-effects meta-analysis model of aggregate published data. Among 21 retrieved documents, 11 studies located in 8 African countries were included in the meta-analysis. Odds ratio of developing epilepsy when presenting cysticercosis (defined as Taenia solium seropositivity) ranged from 1.3-6.1. Overall, association between cysticercosis and epilepsy was found significant with a common odds ratio of 3.4 [95% confidence interval (CI) 2.7-4.3; p < 0.001]. The variability of the association found between the studies could be due to differences in study design or in pathogenesis of cysticercosis. Further studies should overcome identified problems by following some guidelines to improve epidemiologic and clinical assessment of the association. Better understanding of the relation between cysticercosis and epilepsy is a key issue in improving prevention of epilepsy in Africa.

  13. 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

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

    PubMed Central

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

    2013-01-01

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

  15. Association between SNCA rs2736990 polymorphism and Parkinson's disease: a meta-analysis.

    PubMed

    Fang, Jinni; Hou, Binghui; Liu, Hongxin; Zhang, Xiaona; Wang, Jing; Zhou, Chang; Xie, Anmu

    2017-08-24

    Emerging evidence suggests that the SNP rs2736990 of SNCA is a susceptibility factor for idiopathic Parkinson's disease (PD) in different populations, but the studies which examined the association have provided inconsistent results. Therefore, we performed a meta-analysis of some case-control studies to obtain a more exact estimation of there associations. All the relevant studies were extracted from PubMed, Embase, EBSCO, Chineses national knowledge infrastructure, Google Scholar and Wanfang databases (up to February 2017). A total of six studies with 2525 PD cases and 2165 controls were eventually enrolled in the present meta-analysis based on the strict inclusion and exclusion criteria. The pooled analysis showed that there is a significant association between rs2736990 polymorphism and PD susceptibility in all genetic models (T vs. C: OR=0.772, 95%CI: 0.709-0.840, P=0.001; TT vs. CC: OR=0.586, 95%CI: 0.490-0.701, P=0.001; TC vs. CC: OR=0.814, 95%CI: 0.716-0.925, P=0.002; TT+TC vs. CC: OR=0.752, 95%CI: 0.666-0.848, P=0.001; TT vs. TC+CC: OR=0.658, 95%CI: 0.561-0.772, P=0.001). Our meta-analysis provides evidence that the T allele, TT and TC genotype of rs2736990(C/T) polymorphism may decrease the risk of PD. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Associations between matrix metalloproteinase gene polymorphisms and glaucoma susceptibility: a meta-analysis.

    PubMed

    Wu, Ming-Yue; Wu, Yang; Zhang, Yong; Liu, Cai-Yun; Deng, Chun-Yan; Peng, Le; Zhou, Lan

    2017-04-21

    Matrix metalloproteinases (MMPs) polymorphisms have been implicated in the pathogenesis of glaucoma risk. However, the results were controversial. We performed a meta-analysis to evaluate the precise associations between MMPs polymorphisms and glaucoma risk. Related studies were reviewed by searching electronic databases within four databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between the most common polymorphisms of MMPs and glaucoma risk. Heterogeneity, publication bias and sensitivity analysis were conducted to guarantee the statistical power. Overall, 11 selected articles involving 2,388 cases and 2,319 controls were included in this meta-analysis. Significant associations were only found between MMP-9 rs17576 G > A polymorphism (GA vs. GG: OR = 0.80, 95%CI = 0.67-0.97, P = 0.02, I(2) = 0%), MMP-9 rs3918249 C > T polymorphism (TT vs. CC + CT: OR = 0.71, 95%CI = 0.51-0.98, P = 0.04, I(2) = 0%) and glaucoma risk in the general population. Subgroup analysis also suggested that MMP-9 rs17576 G > A was related to glaucoma in the Caucasian population (GA vs. GG: OR = 0.67, 95%CI = 0.45-1.00, P = 0.05; GA + AA vs. GG: OR = 0.66, 95%CI = 0.45-0.97, P = 0.03, I(2) = 0%). Our meta-analysis demonstrates that MMP-9 rs17576 G > A polymorphism might be a protective factor against the development of glaucoma in Caucasian population.

  17. 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.

  18. Association between intake of antioxidants and pancreatic cancer risk: a meta-analysis.

    PubMed

    Chen, Jiamin; Jiang, Wuxia; Shao, Liming; Zhong, Dandan; Wu, Yihua; Cai, Jianting

    2016-11-01

    We conducted a meta-analysis to systematically evaluate the association between antioxidants intake and pancreatic cancer risk. Relevant articles were retrieved from PUBMED and EMBASE databases and standard meta-analysis methods were applied. Finally a total of 18 studies were included. Comparing the highest with lowest categories, higher dietary intakes of selenium, vitamin C, vitamin E, β-carotene and β-cryptoxanthin were significantly associated with reduced pancreatic cancer risk (for selenium, pooled OR = 0.47, 95%CI 0.26-0.85; for vitamin C, pooled OR = 0.68, 95%CI 0.57-0.80; for vitamin E, pooled OR = 0.70, 95%CI 0.62-0.81; for β-carotene, pooled OR = 0.74, 95%CI 0.56-0.98; for β-cryptoxanthin, pooled OR = 0.70, 95%CI 0.56-0.88). Lycopene intake was marginally associated with pancreatic cancer risk (pooled OR = 0.85, 95%CI 0.73-1.00), while no significant association was observed for α-carotene, lutein and zeaxanthin. In summary, higher dietary intake of selenium, vitamin C, vitamin E, β-carotene and β-cryptoxanthin was inversely associated with pancreatic cancer risk.

  19. Dietary fiber intake is inversely associated with risk of pancreatic cancer: a meta-analysis.

    PubMed

    Mao, Qi-Qi; Lin, Yi-Wei; Chen, Hong; Qin, Jie; Zheng, Xiang-Yi; Xu, Xin; Xie, Li-Ping

    2017-01-01

    The association between fiber intake and pancreatic cancer risk is conflicting and poorly explored. The aim of study was to investigate the association between dietary fiber intake and the risk of pancreatic cancer by conducting a meta-analysis of epidemiological studies. Systematic search of PubMed and Embase databases up to April 2015 were conducted to identify relevant studies. Adjusted odds ratios (ORs) were combined using random-effects models to assess the risk of pancreatic cancer when comparing extreme categories of fiber intake. Dose-response meta-analysis was performed for studies reporting categorical risk estimates for at least 3 exposure levels. One cohort and thirteen case-control studies were identified. The overall analysis revealed a strong inverse association between risk of pancreatic cancer and high fiber intake (OR 0.52; 95% CI 0.44-0.61). No publication bias was detected by Egger's or Begg's test. The dose-response analyses showed that the summary OR for an increment of 10 g daily intake of fiber was 0.88 (0.84 to 0.92). A high intake of dietary fiber was associated with a reduced risk of pancreatic cancer. Further well-designed prospective studies are warranted to confirm the inverse association and to identify the dietary fiber types involved.

  20. The association between hot flushes and smoking in midlife women: a meta-analysis.

    PubMed

    Jenabi, E; Poorolajal, J

    2015-01-01

    Several epidemiological studies have investigated the association between hot flushes and smoking, but the results are inconsistent. This meta-analysis was performed to estimate an overall effect of former smoking and current smoking on the risk of hot flushes in midlife women. We searched PubMed, Web of Science, and Scopus for observational studies addressing the association between hot flushes and smoking until March 2015. Data were independently extracted and analyzed using odds ratio with 95% confidence intervals (CI) based on the random-effects model. We identified 621 references and included eight studies with 27 054 participants. The odds ratio of an association between hot flushes and former smoking was estimated as 1.31 (95% CI 1.22-1.41) and that of current smoking was estimated as 1.97 (95% CI 1.81-2.14). No evidence of heterogeneity and publication bias was observed. The findings from this meta-analysis indicated that former and current smoking are associated with an increased risk of hot flushes. However, more evidence based on large, prospective cohort studies is required to provide stronger evidence whether former and current smoking may be associated with an increased risk of hot flushes.

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

    PubMed

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

    2014-06-01

    Domestic animal husbandry, a common practice globally, can lead to zoonotic transmission of enteric pathogens. However, this risk has received little attention to date. This systematic review and meta-analysis examines the evidence for an association between domestic exposure to food-producing animals and cases of human diarrhea and specific enteric infections. We performed a systematic review of available literature to examine domestic livestock and poultry as risk factors for diarrhea and applied pre-determined quality criteria. Where possible, we carried out meta-analysis of specific animal-pathogen pairs. We found consistent evidence of a positive association between exposure to domestic food-producing animals and diarrheal illness across a range of animal exposures and enteric pathogens. Out of 29 studies included in the review, 20 (69.0%) reported a positive association between domestic animal exposure and diarrhea. Domestic exposure to poultry revealed a substantial association with human campylobacteriosis (OR 2.73, 95% CI 1.90-3.93). Our results suggest that domestic poultry and livestock exposures are associated with diarrheal illness in humans. Failure to ascertain the microbial cause of disease may mask this effect. Exposure to domestic animals should be considered a risk factor for human diarrheal illness and additional studies may identify potential mitigation strategies to address this risk. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    PubMed Central

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

    2014-01-01

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

  3. Association between nonverbal communication during clinical interactions and outcomes: a systematic review and meta-analysis.

    PubMed

    Henry, Stephen G; Fuhrel-Forbis, Andrea; Rogers, Mary A M; Eggly, Susan

    2012-03-01

    To conduct a systematic review and meta-analysis of studies reporting associations between patients' and clinicians' nonverbal communication during real clinical interactions and clinically relevant outcomes. We searched 10 electronic databases, reference lists, and expert contacts for English-language studies examining associations between nonverbal communication measured through direct observation and either clinician or patient outcomes in adults. Data were systematically extracted and random effects meta-analyses were performed. 26 observational studies met inclusion criteria. Meta-analysis was performed for patient satisfaction, which was assessed in 65% of studies. Mental and physical health status were evaluated in 23% and 19% of included studies, respectively. Both clinician warmth and clinician listening were associated with greater patient satisfaction (p<0.001 both). Physician negativity was not related to patient satisfaction (p=0.505), but greater nurse negativity was associated with less patient satisfaction (p<0.001). Substantial differences in study design and nonverbal measures existed across studies. Greater clinician warmth, less nurse negativity, and greater clinician listening were associated with greater patient satisfaction. Additional studies are needed to evaluate the impact of nonverbal communication on patients' mental and physical health. Communication-based interventions that target clinician warmth and listening and nurse negativity may lead to greater patient satisfaction. Published by Elsevier Ireland Ltd.

  4. 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

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

    PubMed

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

    2016-09-01

    Cannabis use has been reported to induce long-lasting psychotic disorders and a dose-response relationship has been observed. We performed a systematic review of studies that investigate the association between the degree of cannabis consumption and psychosis and a meta-analysis to quantify the magnitude of effect. Published studies were identified through search of electronic databases, supplemented by manual searches of bibliographies. Studies were considered if they provided data on cannabis consumption prior to the onset of psychosis using a dose criterion (frequency/amount used) and reported psychosis-related outcomes. We performed random effects meta-analysis of individual data points generated with a simulation method from the summary data of the original studies. From 571 references, 18 studies fulfilled inclusion criteria for the systematic review and 10 were inserted in the meta-analysis, enrolling a total of 66 816 individuals. Higher levels of cannabis use were associated with increased risk for psychosis in all the included studies. A logistic regression model gave an OR of 3.90 (95% CI 2.84 to 5.34) for the risk of schizophrenia and other psychosis-related outcomes among the heaviest cannabis users compared to the nonusers. Current evidence shows that high levels of cannabis use increase the risk of psychotic outcomes and confirms a dose-response relationship between the level of use and the risk for psychosis. Although a causal link cannot be unequivocally established, there is sufficient evidence to justify harm reduction prevention programs. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. Consumption of coffee associated with reduced risk of liver cancer: a meta-analysis

    PubMed Central

    2013-01-01

    Background Epidemiologic studies have reported inconsistent results regarding coffee consumption and the risk of liver cancer. We performed a meta-analysis of published case–control and cohort studies to investigate the association between coffee consumption and liver cancer. Methods We searched Medline, EMBASE, ISI Web of Science and the Cochrane library for studies published up to May 2012. We performed a meta-analysis of nine case–control studies and seven cohort studies. Results The summary odds ratio (OR) for high vs no/almost never drinkers was 0.50 (95% confidence interval (CI): 0.42–0.59), with no significant heterogeneity across studies (Q = 16.71; P = 0.337; I2 = 10.2%). The ORs were 0.50 (95% CI: 0.40–0.63) for case–control studies and 0.48 (95% CI: 0.38–0.62) for cohort studies. The OR was 0.38 (95% CI: 0.25–0.56) in males and 0.60 (95% CI: 0.33–1.10) in females. The OR was 0.45 (95% CI: 0.36–0.56) in Asian studies and 0.57 (95% CI: 0.44–0.75) in European studies. The OR was 0.39 (95% CI: 0.28–0.54) with no adjustment for a history of liver disease and 0.54 (95% CI: 0.46–0.66) after adjustment for a history of liver disease. Conclusions The results of this meta-analysis suggested an inverse association between coffee consumption and liver cancer. Because of the small number of studies, further prospective studies are needed. PMID:23433483

  7. Positive association between IL-16 rs1131445 polymorphism and cancer risk: a meta-analysis.

    PubMed

    Liu, Fang-Teng; Zhu, Pei-Qian; Ou, Yang-Xi; Liu, Wan-Wei; Xia, Guang-Feng; Luo, Hong-Liang

    2016-04-01

    The association between IL-16 rs1131445 polymorphism and cancer risk is not consistent or even contradictory, this meta-analysis aims to investigate the role of IL-16 gene rs1131445 polymorphisms in the risk of cancer. A comprehensive online search was conducted in PubMed, EMBASE and CNKI databases to identify eligible studies. The case-control studies related IL-16 rs1131445 C/T polymorphism with the cancer susceptibility were selected according to the inclusion and exclusion criteria. After extracting the basic data information and quality of literature evaluation, the meta-analysis was performed by using STATA 12.0 software, with calculating odds ratio and 95% confidence interval, and further subgroup analysis, literature publication bias test and sensitivity analysis. There are totally 1677 cases and 1989 non-tumor controls finally involved. Meta-analysis showed that there are statistical correlations between the IL-16 rs1131445 C/T polymorphism and the cancer risk in Asian populations (TS vs. C, OR=0.80, 95%CI: 0.73-0.88; TT vs. TC, OR=0.75, 95%CI: 0.65-0.87; TT vs. CC, OR=0.69, 95% CI: 0.56-0.84; CC+TC vs. TT, OR=1.36, 95%CI: 1.19-1.55; CC vs. TC+TT, OR=1.27, 95%CI: 1.05-1.53) (all P<0.05). IL-16 rs1131445 C/T polymorphism is related to the susceptibility to cancer in Asians, suggesting that the C allelic gene of rs1131445 is significantly associated with an increasing cancer risk.

  8. Updated association of tea consumption and bone mineral density: A meta-analysis.

    PubMed

    Zhang, Zhao-Fei; Yang, Jun-Long; Jiang, Huan-Chang; Lai, Zheng; Wu, Feng; Liu, Zhi-Xiang

    2017-03-01

    Current studies evaluating the association of tea consumption and bone mineral density (BMD) have yielded inconsistent findings. Therefore, we conducted a meta-analysis to assess the relationship between tea consumption and BMD. The PubMed, Embase, and Cochrane Library databases were comprehensively searched, and a meta-analysis performed of all observational studies assessing the association of tea consumption and BMD. Forest plots were used to illustrate the results graphically. The Q-test and I statistic were employed to evaluate between-study heterogeneity. Potential publication bias was assessed by the funnel plot. Four cohort, 1 case-control, and 8 cross-sectional studies including a total of 12,635 cases were included. Tea consumption was shown to prevent bone loss [odds ratio (OR): 0.66; 95% confidence interval (CI), 0.47-0.94; P = 0.02], yielding higher mineral densities in several bones, including the lumbar spine [standardized mean difference (SMD): 0.19; 95% CI, 0.08-0.31; P = 0.001], hip (SMD: 0.19; 95% CI, 0.05-0.34; P = 0.01), femoral neck [mean difference (MD): 0.01; 95% CI, 0.00-0.02; P = 0.04], Ward triangle (MD: 0.02; 95% CI, 0.01-0.04; P = 0.001), and greater trochanter (MD: 0.03; 95% CI, 0.02-0.04; P < 0.00001), than the non-tea consumption group. This meta-analysis provided a potential trend that tea consumption might be beneficial for BMD, especially in the lumbar spine, hip, femoral neck, Ward triangle, and greater trochanter, which might help prevent bone loss.

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

    PubMed Central

    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

  10. 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.

  11. 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

  12. Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials.

    PubMed

    Cohen, Stephanie C; Mulqueen, Jilian M; Ferracioli-Oda, Eduardo; Stuckelman, Zachary D; Coughlin, Catherine G; Leckman, James F; Bloch, Michael H

    2015-09-01

    Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials. We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics. We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials. Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant

  13. 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.

  14. 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

  15. 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

  16. Lack of association between factor V Leiden and sepsis: a meta-analysis.

    PubMed

    Zhang, Jing; He, Yanxian; Song, Weibing; Lu, Yong; Li, Ping; Zou, Li; Zhong, Wuzhuang

    2015-04-01

    Some studies evaluated the association of factor V Leiden (FVL) with sepsis risk and mortality risk. However, the results were conflicting. Thus, we performed a meta-analysis to address the association between FVL and sepsis. PubMed and EMBASE databases were searched to find relevant studies. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using random effects model. Five case-control studies and 3 cohort studies were included. Overall, no significant association between FVL and sepsis risk was observed (OR = 0.93; 95% CI 0.74-1.15; P = .49). In addition, there was no significant association between FVL and sepsis-related mortality (OR = 1.17; 95% CI 0.73-1.88; P = .52). In the subgroup analysis, no increased sepsis risk and mortality risk were found in caucasian population. This meta-analysis suggested that FVL was not a risk factor for sepsis and sepsis mortality. © The Author(s) 2013.

  17. 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).

  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. 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.

  20. 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.

  1. Analysis of susceptible genes and chromosome loci for lung cancers by automated gene prediction tools and genome scanning meta-analysis

    PubMed Central

    Tian, Yu; Wang, Daoxin

    2015-01-01

    Genome-wide scanning of susceptible loci and genes for medical diseases is important in current post-genome era. To date, a variety of studies have been focused on the experimental validation or genome-wide linkage scans across multiple populations hunting for susceptibility genes in lung cancer. In the present study, we used two gene prediction tools (PROSPECTR and SUSPECTS, Gen Wanderer) to analyze eight previously identified susceptibility loci for lung tumors, which are selected from literature searching. Our results showed that there was a subset of 26 likely candidate susceptible genes related to lung cancer in each chromosomal region. For potential susceptible chromosome loci, the genome-wide scanning meta-analysis using bins of 60 cM width predicted a group of potential regions associated with lung cancer. Locus 15q21-26 (P=0.000606) is strongly evidenced, which has been confirmed in previous work. In contrast, another potential locus 10q11.2-q23.3 (P=0.0435223) is suggestively evidenced, which was never identified before. Ac compared to previous known regions, the latter one is the new detected one in our study. In conclusion, our study may be useful to contribute to further experimental tests of susceptibility genes/loci related to lung cancer. PMID:26617950

  2. A critical review and meta-analysis of the association between overt hyperthyroidism and mortality.

    PubMed

    Brandt, Frans; Green, Anders; Hegedüs, Laszlo; Brix, Thomas H

    2011-10-01

    Overt hyperthyroidism has been associated with cardiac arrhythmias, hypercoagulopathy, stroke, and pulmonary embolism, all of which may increase mortality. Some, but not all, studies show an increased mortality in patients with hyperthyroidism. This inconsistency may be due to differences in study design, characteristics of participants, or confounders. In order to test whether hyperthyroidism influences mortality, we performed a critical review and statistical meta-analysis. Based on an electronic PubMed search, using the Medical Subject Heading words such as hyperthyroidism, thyrotoxicosis, and mortality or survival, case-control and cohort studies were selected and reviewed. Using meta-analysis, an overall relative risk (RR) of mortality was calculated. Eight studies fulfilled the inclusion criteria, six of which showed an increased all-cause mortality; seven studies, including 31,138 patients and 400,000 person years at risk, allowed calculation of mortality in a meta-analysis. Based on this, the RR of overall mortality was 1.21 (95% confidence interval: 1.05-1.38). Analyses including studies considering setting, treatment, and control for co-morbidity did not significantly alter this finding. As the measured heterogeneity (I(2)) ranges from 89.1 to 98.3%, which is much higher than the 50% generally viewed on as a threshold, the statistical heterogeneity is very pronounced in the included studies. In patients diagnosed with hyperthyroidism, mortality is increased by ∼ 20%. Future studies need to address the cause of hyperthyroidism, impact of type of therapy, time dependency, as well as the potential influence of confounding or genetic susceptibility before the question of causality can be answered.

  3. 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.

  4. 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

  5. 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

  6. The association of Raynaud's syndrome with cisplatin-based chemotherapy - a meta-analysis.

    PubMed

    Mohokum, Melvin; Hartmann, Peter; Schlattmann, Peter

    2012-10-01

    Vasospastic disorders of the digital circulation such as the Raynaud's syndrome (RS) are known side-effects of treatment of cisplatin-based chemotherapy. The prevalence of RS in patients during treatment with cisplatin-based chemotherapy is not well-defined. The objective of this paper was to assess the prevalence of RS in patients receiving cisplatin-based chemotherapy - 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 patients receiving cisplatin-based chemotherapy. The studies provided sufficient data to estimate the prevalence of RS in patients receiving cisplatin-based chemotherapy. 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 and latitude. 24 eligible studies, contributing data on 2749 subjects, were included in this meta-analysis. For RS in patients receiving cisplatin-based chemotherapy a pooled prevalence of 24% and 95% CI (0.175, 0.313) was obtained. A mixture model analysis found four latent classes. Statistically, publication bias was not present (p-value 0.74). The meta-regression indicated that the odds ratio increased when the latitude increased, too (p-value 0.011). Despite some heterogeneity there is a possible indication of an association between RS and patients receiving cisplatin-based chemotherapy. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  7. Association of Common Variants in LOX with Keratoconus: A Meta-Analysis

    PubMed Central

    Hong, Jiaxu; Wu, Dan; Xu, Jianjiang

    2015-01-01

    Background Several case-control studies have been performed to examine the association of genetic variants in lysyl oxidase (LOX) with keratoconus. However, the results remained inconclusive and great heterogeneity might exist across populations. Method A comprehensive literature search for studies that published up to June 25, 2015 was performed. Summary odds ratios (OR) and 95% confidence intervals (CI) of each single nucleotide polymorphism (SNP) were estimated with fixed effects model when I2<50% in the test for heterogeneity or random effects model when I2>50%. Publication bias was evaluated using funnel plots and Egger’s test. Results A total of four studies including 1,467 keratoconus cases and 4,490 controls were involved in this meta-analysis. SNPs rs2956540 and rs10519694 showed significant association with keratoconus, with ORs of 0.71 (95% CI: 0.63–0.80, P = 1.43E-08) and 0.77 (95% CI: 0.61–0.97, P = 0.026), respectively. In contrast, our study lacked sufficient evidences to support the association of rs1800449/rs2288393 with keratoconus across populations. Conclusion This meta-analysis suggested that two LOX variants, rs2956540 and rs10519694, may affect individual susceptibility to keratoconus, while distinct heterogeneity existed within this locus. Larger-scale and multi-ethnic genetic studies on keratoconus are required to further validate the results. PMID:26713757

  8. Association of Common Variants in LOX with Keratoconus: A Meta-Analysis.

    PubMed

    Zhang, Jing; Zhang, Lu; Hong, Jiaxu; Wu, Dan; Xu, Jianjiang

    2015-01-01

    Several case-control studies have been performed to examine the association of genetic variants in lysyl oxidase (LOX) with keratoconus. However, the results remained inconclusive and great heterogeneity might exist across populations. A comprehensive literature search for studies that published up to June 25, 2015 was performed. Summary odds ratios (OR) and 95% confidence intervals (CI) of each single nucleotide polymorphism (SNP) were estimated with fixed effects model when I2<50% in the test for heterogeneity or random effects model when I2>50%. Publication bias was evaluated using funnel plots and Egger's test. A total of four studies including 1,467 keratoconus cases and 4,490 controls were involved in this meta-analysis. SNPs rs2956540 and rs10519694 showed significant association with keratoconus, with ORs of 0.71 (95% CI: 0.63-0.80, P = 1.43E-08) and 0.77 (95% CI: 0.61-0.97, P = 0.026), respectively. In contrast, our study lacked sufficient evidences to support the association of rs1800449/rs2288393 with keratoconus across populations. This meta-analysis suggested that two LOX variants, rs2956540 and rs10519694, may affect individual susceptibility to keratoconus, while distinct heterogeneity existed within this locus. Larger-scale and multi-ethnic genetic studies on keratoconus are required to further validate the results.

  9. 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

  10. 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.

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

    PubMed

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

    2010-09-01

    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 existing studies to boost statistical power. We used data from four projects: a) the Children's Hospital of Philadelphia (CHOP); b) phase I of the International Multicenter ADHD Genetics project (IMAGE); c) phase II of IMAGE (IMAGE II); and d) the Pfizer-funded study from the University of California, Los Angeles, Washington University, and Massachusetts General Hospital (PUWMa). The final sample size consisted of 2,064 trios, 896 cases, and 2,455 controls. For each study, we imputed HapMap single nucleotide polymorphisms, computed association test statistics and transformed them to z-scores, and then combined weighted z-scores in a meta-analysis. No genome-wide significant associations were found, although an analysis of candidate genes suggests that they may be involved in the disorder. Given that ADHD is a highly heritable disorder, our negative results suggest that the effects of common ADHD risk variants must, individually, be very small or that other types of variants, e.g., rare ones, account for much of the disorder's heritability. 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Association between telomere length and diabetes mellitus: A meta-analysis.

    PubMed

    Wang, Jianfei; Dong, Xu; Cao, Li; Sun, Yangyang; Qiu, Yu; Zhang, Yi; Cao, Ruoqiong; Covasa, Mihai; Zhong, Li

    2016-12-01

    Objective We investigated the relationship between diabetes and telomere length by meta-analysis. Methods We searched five popular databases for articles published between 1990 and 2015 using "diabetes" and "telomere" as search terms. Data were processed with RevMan5, and random- or fixed-effects meta-analysis was applied. The effects of geographical region, diabetes type, body mass index (BMI), age and sex were examined. Funnel plots were applied to evaluate publication bias. Results Seventeen articles were obtained from 571 references. We identified a significant association between telomere length and diabetes mellitus (standardized mean difference [SMD]: -3.41; 95% confidence interval [CI]: -4.01, -2.80; heterogeneity, I(2 )= 99%) by comparing 5575 patients with diabetes and 6349 healthy individuals. The pooled SMD by geographic region indicated a significant association between shortened telomere length and diabetes mellitus (SMD: -3.41; 95% CI: -4.01, -2.80; heterogeneity, I(2 )= 99%). In addition, telomere length was significantly associated with age (SMD: -3.41; 95% CI: -4.01, -2.80), diabetes type (SMD: -3.41; 95% CI: -4.01, -2.80), BMI (SMD: -1.61; 95% CI: -1.98, -1.23) and sex (SMD: -4.94; 95% CI: -9.47, -0.40). Conclusions The study demonstrated a close relationship between diabetes mellitus and telomere length, which was influenced by region, age, diabetes type, BMI and sex.

  13. 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

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

    PubMed Central

    Muhsen, Khitam; Levine, Myron M.

    2012-01-01

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

  15. Is weight gain associated with the incidence of periodontitis? A systematic review and meta-analysis.

    PubMed

    Nascimento, Gustavo G; Leite, Fábio R M; Do, Loc G; Peres, Karen G; Correa, Marcos B; Demarco, Flávio F; Peres, Marco A

    2015-06-01

    This study aimed to conduct a systematic review assessing the effects of weight gain on the incidence of periodontitis in adults. Electronic searches in four databases were performed up to and including February 2015. Only prospective longitudinal studies assessing the association between weight gain and the incidence of periodontitis in adults were eligible to be included in this study. All studies should state a clear description of nutritional status (Body Mass Index; Waist Circumference) as well as the case definition of periodontitis. Pooled relative risks (RR) for becoming overweight and obese on the incidence of periodontitis were estimated by meta-analysis. Quality was assessed with the Newcastle-Ottawa scale for cohort studies. Five articles were included in this review and meta-analysis with 42,198 subjects enrolled. Subjects who became overweight and obese presented higher risk to develop new cases of periodontitis (RR 1.13; 95%CI 1.06-1.20 and RR 1.33 95%CI 1.21-1.47 respectively) compared with counterparts who stayed in normal weight. A clear positive association between weight gain and new cases of periodontitis was found. However, these results are originated from limited evidence. Thus, more studies with longitudinal prospective design are needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Associations between Folate and Vitamin B12 Levels and Inflammatory Bowel Disease: A Meta-Analysis.

    PubMed

    Pan, Yun; Liu, Ya; Guo, Haizhuo; Jabir, Majid Sakhi; Liu, Xuanchen; Cui, Weiwei; Li, Dong

    2017-04-13

    Inflammatory bowel disease (IBD) patients may be at risk of vitamin B12 and folate insufficiencies, as these micronutrients are absorbed in the small intestine, which is affected by IBD. However, a consensus has not been reached on the association between IBD and serum folate and vitamin B12 concentrations. In this study, a comprehensive search of multiple databases was performed to identify studies focused on the association between IBD and serum folate and vitamin B12 concentrations. Studies that compared serum folate and vitamin B12 concentrations between IBD and control patients were selected for inclusion in the meta-analysis. The main outcome was the mean difference in serum folate and vitamin B12 concentrations between IBD and control patients. Our findings indicated that the average serum folate concentration in IBD patients was significantly lower than that in control patients, whereas the mean serum vitamin B12 concentration did not differ between IBD patients and controls. In addition, the average serum folate concentration in patients with ulcerative colitis (UC) but not Crohn's disease (CD) was significantly lower than that in controls. This meta-analysis identified a significant relationship between low serum folate concentration and IBD. Our findings suggest IBD may be linked with folate deficiency, although the results do not indicate causation. Thus, providing supplements of folate and vitamin B12 to IBD patients may improve their nutritional status and prevent other diseases.

  17. 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.

  18. 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.

  19. Atrial fibrillation associated with ivabradine treatment: meta-analysis of randomised controlled trials

    PubMed Central

    Martin, Ruairidh I R; Pogoryelova, Oksana; Koref, Mauro Santibáñez; Bourke, John P; Teare, M Dawn; Keavney, Bernard D

    2014-01-01

    Objective To quantify any risk of atrial fibrillation (AF) associated with ivabradine treatment by meta-analysis of clinical trial data. Methods Medline, Embase, Web of Knowledge and the Cochrane central register of controlled trials were searched for double-blinded randomised controlled trials of ivabradine with a minimum follow-up period of 4 weeks. For studies where AF data were unpublished, safety data were obtained from the European Medicines Agency (EMeA) website and personal communications. Studies were appraised for risk of bias using components recommended by the Cochrane Collaboration. Meta-analyses were performed of relative risk of AF and absolute risk difference of AF per year of treatment. The main outcome measure was incident AF during the follow-up period. Results AF data were available from 11 studies: one from the published report, six from the EMeA and four from personal communications. Ivabradine treatment was associated with a relative risk of AF of 1.15 (95% CI 1.07 to 1.24, p=0.0027) among 21 571 patients in the meta-analysis. From this we estimated that the number needed to harm for ivabradine would be 208 (95% CI 122 to 667) per year of treatment. Conclusions AF is a substantially more common side effect of ivabradine treatment than one patient in 10 000, the risk presently reported in the product literature. The incidence of AF has not routinely been reported in clinical trials of ivabradine. PMID:24951486

  20. 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.

  1. Association between p16 Promoter Methylation and Thyroid Cancer Risk: A Meta-analysis.

    PubMed

    Wu, Wei; Yang, Sheng-Fu; Liu, Fei-Fei; Zhang, Ji-Hong

    2015-01-01

    The aim of the meta-analysis was to derive a more precise assessment of the association between p16 promoter methylation and thyroid cancer risk. The PubMed, Web of Science databases and Chinese CNKI were searched for relevant articles. Ultimately, seventeen case-control studies were included with a total of 804 thyroid cancer cases and 487 controls analysis by R Software (R version 3.1.2) including meta. Crude odds ratios with 95% confidence intervals were calculated using the random-effects model which were used to assess the strength of relationship between p16 methylation and lung carcinogenesis. Funnel plots were carried out to evaluate publication bias. The meta-analysis results showed that the frequency of p16 promoter methylation in cancer tissue/blood was significantly higher than that normal tissue/ blood (OR=5.46, 95%CI 3.12-9.55, P<0.0001) by random effects model with small heterogeneity. Thus, p16 promoter methylation may be associated with thyroid cancer risk.

  2. 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.

  3. 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

  4. ADHD is associated with migraine: a systematic review and meta-analysis.

    PubMed

    Salem, Haitham; Vivas, David; Cao, Fei; Kazimi, Iram F; Teixeira, Antonio L; Zeni, Cristian P

    2017-09-13

    An association between primary headaches and attention-deficit/hyperactivity disorder (ADHD) has long been suggested. Moreover, headache is regarded as a common side effect of stimulants, the most effective treatment for ADHD. So far, no systematic review has evaluated the potential association between ADHD and headache. We performed a systematic review of the literature and a meta-analysis of all reported studies on ADHD and primary headaches. Our analysis showed a positive association between ADHD and migraine (OR 1.322, 95% CI 1.018-1717, p value 0.036), but not with tension-type headache. There is a significant association between migraine and ADHD. The mechanisms underlying this association remain to be elucidated, warranting further studies.

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

    PubMed

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

    2016-01-15

    Associations between specific red meat subtypes and risk of colorectal cancer (CRC) have been investigated in a number of epidemiological studies. However, no publication to date has summarised the overall epidemiological evidence. We conducted a systematic review and meta-analysis of prospective studies (cohort, nested case-control or case-cohort studies), which reported relative risk (RR) estimates and 95% confidence intervals (CI) for the association between intake of meat subtypes with colorectal, colon or rectal cancer or colorectal adenoma risk. PubMed and ISI Web of Science were searched up until August 1, 2014. Nineteen studies examined meat subtypes (5 beef, 5 pork, 2 lamb, 1 veal and 19 poultry) and associations with colorectal, colon or rectal cancer risk and 4 studies examined associations with adenoma risk (1 beef and 4 poultry). Comparing highest versus lowest intake, beef consumption was associated with an increased risk of CRC (RR = 1.11, 95% CI = 1.01 to 1.22) and colon cancer (RR = 1.24, 95% CI = 1.07 to 1.44), but no association was found with rectal cancer (RR = 0.95, 95% CI = 0.78 to 1.16). Higher consumption of lamb was also associated with increased risk of CRC (RR = 1.24, 95% CI = 1.08 to 1.44). No association was observed for pork (RR = 1.07, 95% CI = 0.90 to 1.27), but some between study heterogeneity was observed. No association was observed for poultry consumption and risk of colorectal adenomas or cancer. This meta-analysis suggests that red meat subtypes differ in their association with CRC and its sub sites. Further analysis of data from prospective cohort studies is warranted, especially regarding the role of pork. © 2015 UICC.

  6. 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.

  7. The association of placenta previa and assisted reproductive techniques: a meta-analysis.

    PubMed

    Karami, Manoochehr; Jenabi, Ensiyeh; Fereidooni, Bita

    2017-06-06

    Several epidemiological studies have determined that assisted reproductive techniques (ART) can increase the risk of placenta previa. To date, only a meta-analysis has been performed for assessing the relationship between placenta previa and ART. This meta-analysis was conducted to estimate the association between placenta previa and ART in singleton and twin pregnancies. A literature search was performed in major databases PubMed, Web of Science, and Scopus from the earliest possible year to April 2017. The heterogeneity across studies was explored by Q-test and I(2) statistic. The publication bias was assessed using Begg's and Egger's tests. The results were reported using odds ratio (OR) and relative risk (RR) estimates with its 95% confidence intervals (CI) using a random-effects model. The literature search yielded 1529 publications until September 2016 with 1,388,592 participants. The overall estimate of OR was 2.67 (95%CI: 2.01, 3.34) and RR was 3.62 (95%CI: 0.21, 7.03) based on singleton pregnancies. The overall estimate of OR was 1.50 (95%CI: 1.26, 1.74) based on twin pregnancies. We showed based on odds ratio reports in observational studies that ART procedures are a risk factor for placenta previa.

  8. 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

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

    PubMed

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

    2015-01-01

    To provide information about the role of liver fluke infection as a risk factor for hepatobiliary pathological changes and promote awareness among the people living in endemic areas, a systematic review and meta-analysis based on published studies was conducted to examine the association between liver fluke infection and hepatobiliary pathological changes. Relevant original literature was searched in multiple literature databases, including PubMed, Cochrane, Clinical Evidence, Trip Database, Clinical Trials, Current Controlled Trials, Web of Science, the China National Knowledge Infrastructure (CNKI) database, and the Wanfang academic journal full-text database. Studies were selected based on strict screening with inclusion and exclusion criteria. Tests of heterogeneity, sensitivity and publication bias were performed with the Review Manager software, version 5.3, and meta-regression analyses were performed with the Stata software, version 11.0 (Stata Corporation, College Station, TX, USA). Pooled risk ratios (RRs) and odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated and used to evaluate the risk of hepatobiliary pathological changes resulting from liver fluke infection. Linear trend analyses were conducted to determine the dose-response relationship using IBM SPSS Statistics 20.0. A total of 36 studies were included in the meta-analysis. Significant associations were found between liver fluke infection and cholangitis or cholecystitis (RR: 7.80, P<0.001; OR: 15.98, P<0.001), cholelithiasis (RR: 2.42, P = 0.03; OR: 4.96, P = 0.03), hepatocellular carcinoma (OR: 4.69, P<0.001) and cholangiocarcinoma (RR: 10.43, P<0.001; OR: 4.37, P<0.001). In addition, heavier infection was significantly associated with higher incidence of hepatobiliary pathological changes (P<0.05). However, cirrhosis was not significantly associated with liver fluke infection (RR: 3.50, P = 0.06; OR: 5.79, P = 0.08). The statistical heterogeneity was significant, no

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

    PubMed

    Poorolajal, Jalal; Jenabi, Ensiyeh

    2016-05-01

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

  11. Association between compensation status and outcome after surgery: a meta-analysis.

    PubMed

    Harris, Ian; Mulford, Jonathan; Solomon, Michael; van Gelder, James M; Young, Jane

    2005-04-06

    Compensation, whether through workers' compensation or through litigation, has been associated with poor outcome after surgery; however, this association has not been examined by meta-analysis. To investigate the association between compensation status and outcome after surgery. We searched MEDLINE (1966-2003), EMBASE (1980-2003), CINAHL, the Cochrane Controlled Trials Register, and reference lists of retrieved articles and textbooks, and we contacted experts in the field. The review included any trial of surgical intervention in which compensation status was reported and results were compared according to that status. No restrictions were placed on study design, language, or publication date. Studies were selected by 2 unblinded independent reviewers. Two reviewers independently extracted data on study type, study quality, surgical procedure, outcome, country of origin, length and completeness of follow-up, and compensation type. Two hundred eleven studies satisfied the inclusion criteria. Of these, 175 stated that the presence of compensation (workers' compensation with or without litigation) was associated with a worse outcome, 35 found no difference or did not describe a difference, and 1 described a benefit associated with compensation. A meta-analysis of 129 studies with available data (n = 20,498 patients) revealed the summary odds ratio for an unsatisfactory outcome in compensated patients to be 3.79 (95% confidence interval, 3.28-4.37 by random-effects model). Grouping studies by country, procedure, length of follow-up, completeness of follow-up, study type, and type of compensation showed the association to be consistent for all subgroups. Compensation status is associated with poor outcome after surgery. This effect is significant, clinically important, and consistent. Because data were obtained from observational studies and were not homogeneous, the summary effect should be interpreted with caution. Compensation status should be considered a potential

  12. 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. © 2015 Japanese Dermatological Association.

  13. Association between FCGR3B copy number variations and susceptibility to autoimmune diseases: a meta-analysis.

    PubMed

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

    2015-12-01

    This study determined whether FCGR3B copy number variations (CNVs) were associated with susceptibility to autoimmune diseases. A meta-analysis was conducted to determine the association between FCGR3B CNVs and susceptibility to autoimmune diseases by comparing low FCGR3B CN (<2 to ≥2) and high FCGR3B CN (>2 to ≤2). In all, 28 comparative studies from 15 reports involving 12,160 patients and 11,103 controls were included in this meta-analysis. The meta-analysis showed a significant association between low FCGR3B CN and autoimmune diseases (OR=1.496, 95% CI=1.301-1.716, p=1.0×10(-9)). Subgroup analysis according to ethnicity indicated an association between low FCGR3B CN and autoimmune diseases in Caucasians (OR=1.482, 95% CI=1.219-1.801, p=7.7×10(-6)) and Asians (OR=1.498, 95% CI=1.306-1.717, p=1.0×10(-9)). Meta-analysis according to the type of autoimmune disease indicated a significant association of low FCGR3B CN with systemic lupus erythematosus (SLE; OR=1.797, 95% CI=1.562-2.068, p<1.0×10(-9)), primary Sjogren's syndrome (pSS; OR=2.263, 95% CI=1.316-3.892, p=0.003), and Wegener's granulomatosis (WG; OR=1.973, 95% CI=1.178-3.302, p=0.010), but not with rheumatoid arthritis (RA; OR=1.333, 95% CI=0.947-1.877, p=0.099). However, the meta-analysis showed no association between high FCGR3B CN and SLE, RA, pSS, and WG. Thus, the results of this meta-analysis indicated that low FCGR3B CN increased susceptibility to autoimmune diseases, especially SLE, pSS, and WG.

  14. 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.

  15. Associations between interleukin-1 gene polymorphisms and sepsis risk: a meta-analysis

    PubMed Central

    2014-01-01

    Background Previous epidemiological studies have presented conflicting evidence regarding associations between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility. We have performed a meta-analysis to evaluate possible associations between IL-1 polymorphisms and sepsis risk. Methods Eligible literature was retrieved from PubMed, Embase and Web of Knowledge databases until Jun 15, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effects model in the overall and subgroup analysis based on ethnicity, sepsis severity and quality score. Results Eighteen studies addressing five IL-1 polymorphisms were included in this meta-analysis. For IL-1A-889 (rs1800587) polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.47, 95% CI = 1.01-2.13, P = 0.04). There were no significant associations between either IL-1B-511 (rs16944) or IL-1B-31 (rs1143627) and sepsis susceptibility in overall or subgroup analyses. For IL-1B + 3594 (rs143634) polymorphism, genotype TT decreased sepsis risk in overall analysis (OR = 0.59, 95% CI = 0.36-0.97, P = 0.04), as well as in Caucasian (OR = 0.57, 95% CI = 0.34-0.95, P = 0.03) and sepsis (OR = 0.55, 95% CI = 0.31-0.97, P = 0.04) subgroup analysis. For IL-1RN VNTR polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.40, 95% CI = 1.01-1.95, P = 0.04). Furthermore, the effect sizes of IL-1RN VNTR on sepsis risk increased with disease severity (septic shock OR > severe sepsis OR > sepsis OR). Conclusions Our meta-analysis indicated that IL-1A-889, IL-1B + 3954 and IL-1RN VNTR might be associated with sepsis susceptibility. However, further studies with larger sample sizes and from homogenous populations would be necessary to validate these findings. PMID:24428862

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. The association between brain-derived neurotrophic factor gene polymorphism and migraine: a meta-analysis.

    PubMed

    Cai, Xiaoying; Shi, Xiaolei; Zhang, Ximeng; Zhang, Aiwu; Zheng, Minying; Fang, Yannan

    2017-12-01

    Migraine is a recurrent headache disease related to genetic variants. The brain-derived neurotrophic factor (BDNF) gene rs6265 (Val66Met) and rs2049046 polymorphism has been found to be associated with migraine. However, their roles in this disorder are not well established. Then we conduct this meta-analysis to address this issue. PubMed, Web of Science and Cochrane databases were systematically searched to identify all relevant studies. Odds ratio (OR) with corresponding 95% confidence interval (CI) was used to estimate the strength of association between BDNF gene rs6265 and rs2049046 polymorphism and migraine. Four studies with 1598 cases and 1585 controls, fulfilling the inclusion criteria were included in our meta-analysis. Overall data showed significant association between rs6265 polymorphism and migraine in allele model (OR = 0.86, 95%CI: 0.76-0.99, p = 0.03), recessive model (OR = 0.84, 95%CI: 0.72-0.98, p = 0.03) and additive model (GG vs GA: OR = 0.85, 95%CI: 0.72-1.00, p = 0.04), respectively. We also found significant association between rs2049046(A/T) polymorphism and migraine in allele model (OR = 0.88, 95%CI: 0.79-0.98, p = 0.02), recessive model (OR = 0.80, 95%CI: 0.67-0.96, p = 0.02) and additive model (AA vs TT: OR = 0.72, 95%CI: 0.57-0.92, p = 0.008; AA vs AT: OR = 0.81, 95%CI: 0.67-0.99, p = 0.03), respectively. Our meta-analysis suggested that BDNF rs6265 and rs2049046 polymorphism were associated with common migraine in Caucasian population. Further studies are awaited to update this finding in Asian population and other types of migraine.

  1. 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.

  2. 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. © 2013 John Wiley & Sons Ltd.

  3. A Systematic Meta-Analysis of Genetic Association Studies for Diabetic Retinopathy

    PubMed Central

    Abhary, Sotoodeh; Hewitt, Alex W.; Burdon, Kathryn P.; Craig, Jamie E.

    2009-01-01

    OBJECTIVE Diabetic retinopathy is a sight-threatening microvascular complication of diabetes with a complex multifactorial pathogenesis. A systematic meta-analysis was undertaken to collectively assess genetic studies and determine which previously investigated polymorphisms are associated with diabetic retinopathy. RESEARCH DESIGN AND METHODS All studies investigating the association of genetic variants with the development of diabetic retinopathy were identified in PubMed and ISI Web of Knowledge. Crude odds ratios (ORs) and 95% CIs were calculated for single nucleotide polymorphisms and microsatellite markers previously investigated in at least two published studies. RESULTS Twenty genes and 34 variants have previously been studied in multiple cohorts. The aldose reductase (AKR1B1) gene was found to have the largest number of polymorphisms significantly associated with diabetic retinopathy. The z−2 micro satellite was found to confer risk (OR 2.33 [95% CI 1.49–3.64], P = 2 × 10−4) in type 1 and type 2 diabetes and z+2 to confer protection (0.58 [0.36–0.93], P = 0.02) against diabetic retinopathy in type 2 diabetes regardless of ethnicity. The T allele of the AKR1B1 promoter rs759853 variant is also significantly protective against diabetic retinopathy in type 1 diabetes (0.5 [0.35–0.71], P = 1.00 × 10−4), regardless of ethnicity. These associations were also found in the white population alone (P < 0.05). Polymorphisms in NOS3, VEGF, ITGA2, and ICAM1 are also associated with diabetic retinopathy after meta-analysis. CONCLUSIONS Variations within the AKR1B1 gene are highly significantly associated with diabetic retinopathy development irrespective of ethnicity. Identification of genetic risk factors in diabetic retinopathy will assist in further understanding of this complex and debilitating diabetes complication. PMID:19587357

  4. A systematic meta-analysis of genetic association studies for diabetic retinopathy.

    PubMed

    Abhary, Sotoodeh; Hewitt, Alex W; Burdon, Kathryn P; Craig, Jamie E

    2009-09-01

    Diabetic retinopathy is a sight-threatening microvascular complication of diabetes with a complex multifactorial pathogenesis. A systematic meta-analysis was undertaken to collectively assess genetic studies and determine which previously investigated polymorphisms are associated with diabetic retinopathy. All studies investigating the association of genetic variants with the development of diabetic retinopathy were identified in PubMed and ISI Web of Knowledge. Crude odds ratios (ORs) and 95% CIs were calculated for single nucleotide polymorphisms and microsatellite markers previously investigated in at least two published studies. Twenty genes and 34 variants have previously been studied in multiple cohorts. The aldose reductase (AKR1B1) gene was found to have the largest number of polymorphisms significantly associated with diabetic retinopathy. The z-2 microsatellite was found to confer risk (OR 2.33 [95% CI 1.49-3.64], P = 2 x 10(-4)) in type 1 and type 2 diabetes and z+2 to confer protection (0.58 [0.36-0.93], P = 0.02) against diabetic retinopathy in type 2 diabetes regardless of ethnicity. The T allele of the AKR1B1 promoter rs759853 variant is also significantly protective against diabetic retinopathy in type 1 diabetes (0.5 [0.35-0.71], P = 1.00 x 10(-4)), regardless of ethnicity. These associations were also found in the white population alone (P < 0.05). Polymorphisms in NOS3, VEGF, ITGA2, and ICAM1 are also associated with diabetic retinopathy after meta-analysis. Variations within the AKR1B1 gene are highly significantly associated with diabetic retinopathy development irrespective of ethnicity. Identification of genetic risk factors in diabetic retinopathy will assist in further understanding of this complex and debilitating diabetes complication.

  5. 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

  6. The Association between ANXA11 Gene Polymorphisms and Sarcoidosis: a Meta-Analysis and systematic review.

    PubMed

    Zhou, Hongfei; Diao, Mengyuan; Zhang, Mingyue

    2016-08-01

    The associations of ANXA11 gene polymorphisms and susceptibility to sarcoidosis have been evaluated in recent years. However, the results remain controversial, especially in different ethnicity. To assess the associations between ANXA11 and sarcoidosis, we conducted this meta-analysis. Articles were searched in MEDLINE, EMBASE and PubMed from their establishment date to August of 2014, and 4,567 sarcoidosis patients and 4,278 controls from 6 studies were included. The strength of associations was determined by ORs with 95% CIs. The associations between ANXA11 SNP rs1049550, rs2573346, rs2789679 polymorphisms and sarcoidosis risk were assessed using additive, recessive and dominant models. ANXA11 SNP rs2573346 and rs2789679 T allele conferred protection against sarcoidosis (OR: 0.664, 95% CI: 0.607-0.726 for rs2573346, and OR: 0.698, 95% CI: 0.640-0.762 for rs2789679). For SNP rs1049550, individuals carrying the ''T'' allele (TT+CT) had a nearly 46% increased risk for the development of sarcoidosis, when compared with CC homozygotes (OR: 1.461, 95% CI: 1.183-1.803) in overall population. A significant association was also found in additive model (OR: 1.477, 95% CI: 1.328-1.642 for CC vs. CT; OR: 0.610, 95% CI: 0.412-0.905 for TT vs. CC). In addition, ethnicity factors may contribute to the disease risk. The meta-analysis revealed that ''T'' allele of ANXA11 SNP rs2573346 and rs2789679 conferred protection against sarcoidosis. ''C'' allele of SNP rs1049550 may be a risk factor for sarcoidosis in overall population. Our study shows that ANXA11 closely associated with the development of sarcoidosis but further studies in different ethnicity were needed.

  7. 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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24844784

  9. 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. © 2016 John Wiley & Sons Ltd/University College London.

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

    PubMed Central

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

    2015-01-01

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

  11. Association between three eNOS polymorphisms and cancer risk: a meta-analysis.

    PubMed

    Wu, Xun; Wang, Zhi-Feng; Xu, Yin; Ren, Rui; Heng, Bao-Li; Su, Ze-Xuan

    2014-01-01

    Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may influence the risk of cancer, but the results are still debatable. Therefore, we performed a systematic review to provide a more complete picture and conducted a meta-analysis to derive a precise estimation. We searched PubMed, EMBASE, EBSCO, Google Scholar and China National Knowledge Infrastructure (CNKI) databases until April 2014 to identify eligible studies. Thirty-one studies with cancer patients and controls were included in the meta-analysis. Overall, the polled analysis revealed that the T-786C polymorphism was significantly associated with increased cancer risk under multiple genetic models (C vs T: OR=1.135, 95%CI=1.048-1.228; CC vs TT: OR=1.278, 95%CI=1.045- 1.562; TC vs TT: OR=1.136, 95%CI=1.023-1.261; CC+TC vs TT: OR=1.159, 95%CI=1.047-1.281; CC vs TC+TT: OR=1.204, 95%CI= 1.003-1.447). G894T was associated with significant risk for females (TT vs GG: OR=1.414, 95%CI=1.056-1.892; TT vs GT+GG: OR=1.356, 95%CI=1.108-1.661) and for breast cancer (T vs G: OR=1.097, 95%CI=1.001-1.203; TT vs GG: OR=1.346, 95%CI=1.012-1.789; TT vs GT+GG: OR=1.269, 95%CI=1.028-1.566). Increased susceptibility was revealed for prostate cancer with 4a/b (ba vs bb: OR=1.338, 95%CI=1.013-1.768; aa+ba vs bb: OR=1.474, 95%CI=1.002-2.170). This meta-analysis indicated that the eNOS T-786C polymorphism is associated with elevated cancer risk; the G894T polymorphism contributes to susceptibility to breast cancer and cancer generally in females; and the 4a/b polymorphism may be associated with prostate cancer risk.

  12. Association between nutritional status and dengue infection: a systematic review and meta-analysis.

    PubMed

    Trang, Nguyen Thi Huyen; Long, Nguyen Phuoc; Hue, Tran Thi Minh; Hung, Le Phi; Trung, Tran Dinh; Dinh, Doan Ngoc; Luan, Nguyen Thien; Huy, Nguyen Tien; Hirayama, Kenji

    2016-04-20

    Dengue infection has various clinical manifestations, often with unpredictable clinical evolutions and outcomes. Several factors including nutritional status have been studied to find the relationship with dengue severity. However, the nutritional status had conflicting effects on the complication of dengue in some previous studies. Therefore, we conducted a systematic review and performed a meta-analysis to analyze the association between nutritional status and the outcome of dengue infection. Eleven electronic databases and manual searching of reference lists were used to identify the relevant studies published before August 2013. At least two authors worked independently in every step to select eligible studies and extract data. Dengue severity in the included studies must be classified into three categories: dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Thirteen articles that met the inclusion criteria came to final analysis. A meta-analysis using fixed- or random-effects models was conducted to calculate pooled odds ratios (OR) with corresponding 95 % confidence intervals. It has shown that there was no statistically significant association between DHF group and DSS group in malnutritional and overweight/obesity patients with OR: 1.17 (95 % CI: 0.99-1.39), 1.31 (0.91-1.88), respectively. A significantly inverse relation between DF and DHF groups of malnutritional patients was revealed (OR = 0.71, 95 % CI: 0.56-0.90). Our meta-analysis also indicated a statistically significant negative correlation between malnourished children with dengue virus infection and healthy children (OR = 0.46, 95 % CI: 0.3-0.70). When analyzing patients with normal nutrition status, we found out that there was a significantly negative relationship between DHF and DSS groups (0.87; 95 % CI: 0.77-0.99). Other comparisons of DSS with DF/DHF groups, DSS/DHF with DF groups, and DHF with DF groups in normal nutritional patients showed no

  13. 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.

  14. Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea.

    PubMed

    Szajewska, H; Kołodziej, M

    2015-10-01

    Antibiotic-associated diarrhoea is a common complication of antibiotic use, but it can be prevented with administration of probiotics. To update our 2005 meta-analysis on the effectiveness of Saccharomyces boulardii in preventing antibiotic-associated diarrhoea in children and adults. The Cochrane Library, MEDLINE, and EMBASE databases were searched up until May 2015, with no language restrictions, for randomised controlled trials; additional references were obtained from reviewed articles. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Twenty-one randomised controlled trials (4780 participants), among which 16 were new trials, met the inclusion criteria for this updated systematic review. Administration of S. boulardii compared with placebo or no treatment reduced the risk of antibiotic-associated diarrhoea (as defined by the study investigators) in patients treated with antibiotics from 18.7% to 8.5% (risk ratio, RR: 0.47; 95% CI: 0.38-0.57, number needed to treat, NNT: 10; 95% CI: 9-13). In children, S. boulardii reduced the risk from 20.9% to 8.8% (6 randomised controlled trials, n=1653, RR: 0.43, 95% CI: 0.3-0.6); in adults, from 17.4% to 8.2% (15 randomised controlled trials, n=3114, RR: 0.49, 95% CI: 0.38-0.63). Moreover, S. boulardii reduced the risk of Clostridium difficile-associated diarrhoea; however, this reduction was significant only in children (2 randomised controlled trials, n = 579, RR: 0.25; 95% CI: 0.08-0.73) and not in adults (9 randomised controlled trials, n = 1441, RR: 0.8, 95% CI: 0.47-1.34). This meta-analysis confirms that S. boulardii is effective in reducing the risk of antibiotic-associated diarrhoea in children and adults. © 2015 John Wiley & Sons Ltd.

  15. Association between physical activity and mortality in breast cancer: a meta-analysis of cohort studies.

    PubMed

    Zhong, Shanliang; Jiang, Tianchi; Ma, Tengfei; Zhang, Xiaohui; Tang, Jinhai; Chen, Weixian; Lv, Mengmeng; Zhao, Jianhua

    2014-06-01

    Previous studies concerning the association between physical activity (PA) and mortality in breast cancer yielded mixed results. We investigated the association by performing a meta-analysis of all available studies. Relevant studies were identified by searching PubMed and EMBASE to January 2014. We calculated the summary relative risk (RR) and 95 % confidence intervals (CIs) using random-effects models. The dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. Sixteen cohort studies involving 42,602 patients of breast cancer were selected for meta-analysis. The analyses showed that patients who participated in any amount of PA before diagnosis had a RR of 0.82 (95 % CI 0.74-0.91) for breast cancer-specific mortality (vs. low PA). Those who participated in high PA and moderate PA before diagnosis had a RR of breast cancer-specific mortality of 0.81 (95 % CI 0.72-0.90) and 0.83 (95 % CI 0.73-0.94), respectively. Similar inverse associations of prediagnosis PA were found for all-cause mortality. Postdiagnosis PA on breast cancer-specific and all-cause mortality also showed the same results. Stratifying by body mass index (<25 vs. ≥25) or menopausal status, all the subgroups experienced benefits with PA, with a stronger mortality reduction among overweight women than normal weight women and among postmenopausal women than premenopausal women. A linear and significant dose-response association was only found for breast cancer-specific or all-cause mortality and prediagnosis PA (P for nonlinearity = 0.07 and 0.10, respectively). In conclusion, both prediagnosis and postdiagnosis PA were associated with reduced breast cancer-specific mortality and all-cause mortality.

  16. [A Meta analysis on the associations between air pollution and respiratory mortality in China].

    PubMed

    Liu, Changjing; Huang, Fei; Yang, Zhizhou; Sun, Zhaorui; Huang, Changbao; Liu, Hongmei; Shao, Danbing; Zhang, Wei; Ren, Yi; Tang, Wenjie; Han, Xiaoqin; Nie, Shinan

    2015-08-01

    To analyze the associations between air pollution and adverse health outcomes on respiratory diseases and to estimate the short-term effects of air pollutions [Particulate matter with particle size below 10 microns (PM(10)), PM(10) particulate matter with particle size below 2.5 microns (PM(2.5)), nitrogen dioxide (NO₂), sulphur dioxide (SO₂) and ozone (O₃)] on respiratory mortality in China. Data related to the epidemiological studies on the associations between air pollution and adverse health outcomes of respiratory diseases that published from 1989 through 2014 in China, were collected by systematically searching databases of PubMed, SpringerLink, Embase, Medline, CNKI, CBM and VIP in different provinces of China. Short-term effects between (PM(10), PM(2.5), NO₂, SO₂, O₃) and respiratory mortality were analyzed by Meta-analysis method, and estimations were pooled by random or fixed effect models, using the Stata 12.0 software. A total of 157 papers related to the associations between air pollution and adverse health outcomes of respiratory diseases in China were published, which covered 79.4% of all the provinces in China. Results from the Meta-analysis showed that a 10 µg/m³ increase in PM10, PM(2.5), NO₂, SO₂, and O₃was associated with mortality rates as 0.50% (95% CI: 0-0.90%), 0.50% (95% CI: 0.30%-0.70%), 1.39% (95% CI: 0.90%-1.78%), 1.00% (95% CI: 0.40%-1.59%) and 0.10% (95% CI: -1.21%-1.39%) in respiratory tracts, respectively. No publication bias was found among these studies. There seemed positive associations existed between PM(10)/PM(2.5)/NO₂/SO₂and respiratory mortality in China that the relationship called for further attention on air pollution and adverse health outcomes of the respiratory diseases.

  17. 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

  18. 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

  19. Association of atopic dermatitis with smoking: A systematic review and meta-analysis.

    PubMed

    Kantor, Robert; Kim, Ashley; Thyssen, Jacob P; Silverberg, Jonathan I

    2016-12-01

    Tobacco exposure might be a modifiable risk factor for atopic dermatitis (AD). We examine the association between AD and exposure to tobacco smoke. We performed a systematic review and meta-analysis of observational studies (n = 86) in MEDLINE, EMBASE, Scopus, and Cochrane Library (1823-2015). Quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS). A meta-analysis was performed using random-effects models to estimate pooled odds ratios (OR). Subset analyses were performed for different ages (children, adult), regions, study designs (cross-sectional, longitudinal), study sizes (<5000, ≥5000), study quality (NOS score <6, ≥6), and amount of smoking (mild, extensive). A diagnosis of AD was associated with higher odds of active smoking (OR 1.87, 95% confidence interval 1.32-2.63) and exposure to passive smoke (OR 1.18, 95% confidence interval 1.01-1.38), but not maternal smoking during pregnancy (OR 1.06, 95% confidence interval 0.80-1.40). The association between active smoking and AD remained significant in children and adults, all continents studied, and study sizes, but all were cross-sectional designs and had NOS score 6 or greater. Passive smoke was associated with AD in children and adults, cross-sectional studies, South/Central American and African studies, study size less than 5000, and NOS score less than 6. AD severity and distribution were not assessed. Active and passive exposure to smoke are associated with increased AD prevalence. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  20. Association between nonalcoholic fatty liver disease and colorectal adenoma: a systemic review and meta-analysis.

    PubMed

    Shen, Huafeng; Lipka, Seth; Kumar, Ambuj; Mustacchia, Paul

    2014-12-01

    Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome (MetS) and the most common chronic liver disease worldwide. The association between NAFLD and colorectal adenoma has been investigated in multiples studies but the results have been conflicting. We performed a systematic review and meta-analysis to evaluate this in asymptomatic patients who underwent screening colonoscopy. We searched the literatures of all languages from PubMed, EMBASE and the Cochrane library from January 1, 1980 through July 15, 2014. Combined and subgroup analyses stratified by study designs, study locations, characteristics of adenoma (location, size, number, and advanced adenoma) were performed. Four cross-sectional and one cohort studies with a total of 6,263 subjects were included in the meta-analysis. NAFLD was significantly associated with colorectal adenoma [pooled odds ratio (OR) 1.74, 95% confidence interval (CI): 1.53-1.97]. The association was more significant in Asian population (pooled OR =1.77, 95% CI: 1.52-2.05, n=3 studies), compared to European/North American population (pooled OR =1.42, 95% CI: 0.75-2.67, n=2 studies). NAFLD was significantly associated with the number of colorectal adenoma (pooled OR =1.78, 95% CI: 1.10-2.86, n=2 studies), but not the location, size, or presence of advanced adenoma. Our results suggest NAFLD is significantly associated with the presence of colorectal adenoma in asymptomatic patients undergoing screening colonoscopy. This finding provides additional risk stratifications for applying colorectal cancer (CRC) screening strategies. However, more studies of western population are needed to further investigate the ethnic disparity.

  1. A systematic review and meta-analysis of the association between systemic fluoroquinolones and retinal detachment.

    PubMed

    Alves, Carlos; Penedones, Ana; Mendes, Diogo; Batel Marques, Francisco

    2016-08-01

    Several pharmacoepidemiologic studies have been carried out evaluating the risk of retinal detachment associated with systemic fluoroquinolones. This meta-analysis aims to investigate such association, in the light of the best scientific evidence available. A literature search was conducted to identify relevant studies evaluating the risk for retinal detachment associated with systemic fluoroquinolones. A meta-analysis was performed to pool rate ratios (RRs). Meta-regressions were conducted aiming to evaluate the influence of time interval between fluoroquinolones use and retinal detachment diagnosis or treatment risk estimates. Ten observational studies from seven publications were included. Overall, fluoroquinolones were not associated with an increased risk for retinal detachment [RR 1.47 (95% CI 0.95-2.27): p = 0.09; I(2)  = 92.8%]. When the analysis was stratified according to different study designs, the result was statistically significant for retrospective cohort studies [RR 1.87 (95% CI 1.36-2.58); p < 0.001; I(2)  = 0.0%] and for past users of fluoroquinolones, based on data from case-control studies [RR 1.07 (95% CI 1.01-1.12); p = 0.01; I(2)  = 0.0%]. According to meta-regressions, the risk for retinal detachment did not vary due to different time intervals between fluoroquinolones prescription and retinal detachment occurrence. No statistically significant results were identified among studies evaluating only rhegmatogenous retinal detachments, as well as among studies that evaluated patients not requiring a prior ophthalmologist visit to be included. In light of the current available evidence, systemic fluoroquinolones do not seem to be associated with retinal detachment. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  2. Associations of welding and manganese exposure with Parkinson disease: review and meta-analysis.

    PubMed

    Mortimer, James A; Borenstein, Amy R; Nelson, Lorene M

    2012-09-11

    To examine associations of welding and manganese exposure with Parkinson disease (PD) using meta-analyses of data from cohort, case-control, and mortality studies. Epidemiologic studies related to welding or manganese exposure and PD were identified in a PubMed search, article references, published reviews, and abstracts. Inclusion criteria were 1) cohort, case-control, or mortality study with relative risk (RR), odds ratio (OR), or mortality OR (MOR) and 95 confidence intervals (95% CI); 2) RR, OR, and MOR matched or adjusted for age and sex; 3) valid study design and analysis. When participants of a study were a subgroup of those in a larger study, only results of the larger study were included to assure independence of datasets. Pooled RR/OR estimates and 95% CIs were obtained using random effects models; heterogeneity of study effects were evaluated using the Q statistic and I(2) index in fixed effect models. Thirteen studies met inclusion criteria for the welding meta-analysis and 3 studies for the manganese exposure meta-analysis. The pooled RR for the association between welding and PD for all study designs was 0.86 (95% CI 0.80-0.92), with absence of between-study heterogeneity (I(2) = 0.0). Effect measures for cohort, case-control, and mortality studies were similar (0.91, 0.82, 0.87). For the association between manganese exposure and PD, the pooled OR was 0.76 (95% CI 0.41-1.42). Welding and manganese exposure are not associated with increased PD risk. Possible explanations for the inverse association between welding and PD include confounding by smoking, healthy worker effect, and hormesis.

  3. Human endogenous retrovirus HERV-Fc1 association with multiple sclerosis susceptibility: a meta-analysis.

    PubMed

    de la Hera, Belén; Varadé, Jezabel; 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

    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. 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. 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)]. Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts.

  4. 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

  5. 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

  6. 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

  7. Association Between Asthma and Periodontal Disease: A Systematic Review and Meta-Analysis.

    PubMed

    Moraschini, Vittorio; de Albuquerque Calasans-Maia, José; Diuana Calasans-Maia, Monica

    2017-09-05

    The aim of this systematic review is to evaluate the association between asthma and periodontal disease. An electronic search without date or language restrictions ​​was carried out in MEDLINE, Cochrane, Web of Science, and LILACS until May 2016. In addition, manual search and in the grey literature were also conducted. The search process, data analysis, and quality assessment were performed by two independent reviewing authors. Eligibility criteria included prospective and retrospective cohort studies, case-controls, and randomized clinical trials. The search and selection process yielded 21 studies, published between 1979 and 2017. The meta-analysis showed a statistically significant difference for the parameters of gingival bleeding, plaque index, and gingival index for asthmatic participants with P<0.0001, P<0.0001, and P= 0.0005, respectively. The data from this systematic review strongly suggest the association of asthma with periodontal disease.

  8. Genetic associations for keratoconus: a systematic review and meta-analysis.

    PubMed

    Rong, Shi Song; Ma, Sarah Tsz Ue; Yu, Xin Ting; Ma, Li; Chu, Wai Kit; Chan, Tommy Chung Yan; Wang, Yu Meng; Young, Alvin L; Pang, Chi Pui; Jhanji, Vishal; Chen, Li Jia

    2017-07-04

    Genetic associations for keratoconus could be useful for understanding disease pathogenesis and discovering biomarkers for early detection of the disease. We conducted a systematic review and meta-analysis to summarize all reported genetic associations for the disease. We searched in the MEDLINE, Embase, Web of Science, and HuGENET databases for genetic studies of keratoconus published from 1950 to June 2016. The summary odds ratio and 95% confidence intervals of all polymorphisms were estimated using the random-effect model. Among 639 reports that were retrieved, 24 fulfilled required criteria as eligible studies for meta-analysis, involving a total of 53 polymorphisms in 28 genes/loci. Results of our meta-analysis lead to the prioritization of 8 single-nucleotide polymorphisms (SNPs) in 6 genes/loci for keratoconus in Whites. Of them 5 genes/loci were originally detected in genome-wide association studies, including FOXO1 (rs2721051, P = 5.6 × 10(-11)), RXRA-COL5A1 (rs1536482, P = 2.5 × 10(-9)), FNDC3B (rs4894535, P = 1.4 × 10(-8)), IMMP2L (rs757219, P = 6.1 × 10(-7); rs214884, P = 2.3 × 10(-5)), and BANP-ZNF469 (rs9938149, P = 1.3 × 10(-5)). The gene COL4A4 (rs2229813, P = 1.3 × 10(-12); rs2228557, P = 4.5 × 10(-7)) was identified in previous candidate gene studies. We also found SNPs in 10 genes/loci that had a summary P value < 0.05. Sensitivity analysis indicated that the results were robust. Replication studies and understanding the roles of these genes in keratoconus are warranted.

  9. Associations of Parenting Dimensions and Styles with Externalizing Problems of Children and Adolescents: An Updated Meta-Analysis

    ERIC Educational Resources Information Center

    Pinquart, Martin

    2017-01-01

    The present meta-analysis integrates research from 1,435 studies on associations of parenting dimensions and styles with externalizing symptoms in children and adolescents. Parental warmth, behavioral control, autonomy granting, and an authoritative parenting style showed very small to small negative concurrent and longitudinal associations with…

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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.

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

    PubMed

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

    2016-01-01

    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. Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015). Study-specific risk estimates were pooled under the random-effects model. 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). 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.

  19. Alopecia and its association with coronary heart disease and cardiovascular risk factors: a meta-analysis.

    PubMed

    Trieu, Nelson; Eslick, Guy D

    2014-10-20

    Alopecia has been associated with an increased risk of coronary heart disease as well as the following risk factors for cardiovascular disease: hyperinsulinaemia, insulin resistance, metabolic syndrome, dyslipidaemia, and hypertension. We performed a meta-analysis to quantitatively determine the level of risk of coronary heart disease and risk factors in individuals with alopecia. A systematic literature search was conducted using several databases. We calculated pooled odds ratios and 95% confidence intervals using a random effects model. In total, 31 studies comprising 29,254 participants with alopecia were eligible for the meta-analysis and showed that alopecia is associated with an increased risk of coronary heart disease (OR 1.22, 95% CI: 1.07-1.39), hyperinsulinaemia (OR 1.97, 95% CI: 1.20-3.21), insulin resistance (OR 4.88, 95% CI: 2.05-11.64), and metabolic syndrome (OR 4.49, 95% CI: 2.36-8.53). Individuals with alopecia were also shown to be more likely compared to those without alopecia to have higher serum cholesterol levels (OR 1.60, 95% CI: 1.17-2.21), higher serum triglyceride levels (OR 2.07, 95% CI: 1.32-3.25), higher systolic blood pressures (OR 1.73, 95% CI: 1.29-2.33), and higher diastolic blood pressures (OR 1.59, 95% CI: 1.16-2.18). Alopecia is associated with an increased risk of coronary heart disease, and there appears to be a dose-response relationship with degree of baldness whereby the greater the severity of alopecia, the greater the risk of coronary heart disease. Alopecia is also associated with an increased risk of hypertension, hyperinsulinaemia, insulin resistance, metabolic syndrome, and having elevated serum total cholesterol and triglyceride levels. Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.

  20. CD226 Gly307Ser association with multiple autoimmune diseases: a meta-analysis.

    PubMed

    Qiu, Zhi-Xin; Zhang, Kui; Qiu, Xue-Song; Zhou, Min; Li, Wei-Min

    2013-02-01

    Recently, there has been increasing evidence shown that a non-synonymous exchange (Gly307Ser/rs763361) of the CD226 gene on chromosome 18q22 is linked to several autoimmune diseases (ADs) including type 1 diabetes (T1D), celiac disease (CED), rheumatoid arthritis (RA), multiple sclerosis (MS), Grave's disease, Wegener's granulomatosis (WG), psoriasis, and primary sicca syndrome (pSS). Taking into consideration that different autoimmune diseases may share some common pathogenic pathways and in order to assess the overall relationship between CD226 Gly307Ser (rs763361) polymorphism and multiple autoimmune diseases, we performed this meta-analysis. All eligible case-control studies were searched in the US National Library of Medicine's PubMed and Embase database. Crude odds ratios (OR) with 95% confidence intervals (CI) were conducted to assess the association. 7876 cases and 8558 controls from 7 published studies which were selected from 149 articles identified by a search of the US National Library of Medicine's PubMed and Embase databases for the period up to 25th April 2012. The total OR for ADs associated with the T allele was 1.19 (95%CI=1.12-1.27) by random effects model. Significantly increased risks were also observed in the South American (OR=1.72, 95%CI=1.34-2.20), Asian (OR=1.46, 95%CI=1.01-2.10), and European (OR=1.29, 95%CI=1.07-1.58). Similarly, significant associations were observed in two genetic models (OR=1.41, 95%CI=1.23-1.62 in a codominant model; OR=1.33, 95%CI=1.18-1.50 in a recessive model). This meta-analysis provided evidence that CD226 Gly307Ser (rs763361) is significantly associated with the risk of multiple autoimmune diseases. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  1. 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

  2. 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

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

    PubMed

    Du, Xing-Li; Liu, Lei; Song, Wen; Zhou, Xiang; Lv, Zheng-Tao

    2016-01-01

    The aim of this systematic review and meta-analysis was to assess the possible association between gout and erectile dysfunction (ED). 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. 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. 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.

  4. 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

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

    PubMed Central

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

    2013-01-01

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

  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. No association between COMT val158met polymorphism and suicidal behavior: meta-analysis and new data

    PubMed Central

    2011-01-01

    Background The polymorphism COMTval158met has been associated with suicidal behavior in case-control and meta-analysis studies, but results and conclusions remain controversial. The objective of this study was to examine the association between COMT val158met 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 with 105 patients with suicide attempts and 236 controls. Subsequently, we performed a meta-analysis of published genetic association studies by searching through Medline, PubMed and Web of Science databases. Results No significant differences were found in the distribution of alleles (χ2 = 0.33, 1 df, p = 0.56) or genotypes (χ2 = 2.36, 2 df, p = 0.26). The meta-analysis comprising 12 association studies (including the present one) showed that the risk COMTmet allele of COMTval158/met is not associated with suicidal behavior (OR: 1.09, 95% CI: 0.97-1.23), even in the absence of heterogeneity (OR: 1.09, 95% CI: 0.97-1.23). Conclusion Our results showed no association between COMTval158/met and suicidal behavior. However, more studies are necessary to determine conclusively an association between COMT and suicidal behavior. PMID:21936936

  8. Association between MASP-2 gene polymorphism and risk of infection diseases: A meta-analysis.

    PubMed

    Fu, Jie; Wang, Jingqiu; Luo, Yanping; Zhang, Lifeng; Zhang, Yuan; Dong, Xinfang; Yu, Hongjuan; Cao, Mingqiang; Ma, Xingming

    2016-11-01

    The role of MASP-2 is vital in the process of complement activation by the lectin pathway. It is generally considered that the functional activation of MASP-2 contribute to the infection disease development process. To analyze the association between MASP-2 functional gene (rs72550870) polymorphism and the infection disease risk by a meta-analysis. Relevant case-control studies were identified by searching Cochrane Library, PubMed, Emabase, DOAJ, CAB Abstracts, CSA, CINAHL, EBSCO, Scopus, Global Health, Index Copernicus, CA, China National Knowledge Infrastructure (CNKI) databases up to 10th January 2016. The data were extracted and the methodological quality of studies were evaluated. The STATA 12.0 software was used to perform statistical analysis. 9 studies were included. There was no significant association between masp-2 gene (p.D120G, rs72550870) polymorphism and the risk of infection disease under the allele model (G vs. A: OR = 0.89, 95%CI = 0.66-1.21)(P = 0.445>0.05) and the recessive model (AG + GG vs.AA: OR = 0.88, 95%CI = 0.65-1.20) (P = 0.428>0.05). This is the first comprehensive meta-analysis indicates that the MASP-2 functional gene (rs72550870) polymorphism is not associated with the infection diseases, and the key functional gene polymorphism of rs72550870 did not increase susceptibility to the infection diseases. Similarly, there were no obvious difference in subgroup analysis based on geographical areas and pathogenic microorganisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Meta-analysis of incidence and risk of peripheral neuropathy associated with intravenous bortezomib.

    PubMed

    Peng, Ling; Ye, Xianghua; Zhou, Yun; Zhang, Junyan; Zhao, Qiong

    2015-09-01

    Bortezomib is a proteasome inhibitor which has demonstrated activity against recurrent or newly diagnosed multiple myeloma (MM) and mantle cell lymphoma. Peripheral neuropathy has been described with this agent, although the overall incidence and relative risk remain unclear. We performed a meta-analysis to calculate the incidence of peripheral neuropathy associated with the use of intravenous bortezomib in MM and lymphoma and to compare the relative risk compared with placebo. We searched PubMed, Embase, Cochrane databases, and meeting proceedings from the American Society of Clinical Oncology (ASCO) for relevant clinical trials. Eligible studies included prospective phase 2 and 3 clinical trials with toxicity profile on peripheral neuropathy associated with intravenous bortezomib in patients with MM and lymphoma. Statistical analyses were done to calculate summary incidences, relative risks (RRs), and 95 % confidence intervals (CIs), employing fixed- or random-effects models depending on the heterogeneity of the included studies. Altogether, 34 clinical trials were selected for the meta-analysis, yielding a total of 6492 patients. The incidence of peripheral neuropathy (all grades) was 33.9 % (95 % CI, 29.9-38.5 %) and that of high-grade events was 8.1 % (95 % CI, 6.9-9.4 %). The relative risks of bortezomib-induced peripheral neuropathy compared to placebo were increased for all-grade (RR = 4.89; 95 % CI, 2.52-9.51) and high-grade (RR = 4.53; 95 % CI, 2.04-10.07) peripheral neuropathy (for randomized controlled trials only). Our analysis was also stratified by different underlying diseases, and patients with lymphoma had an increased incidence of all-grade peripheral neuropathy than those with MM when treated with intravenous bortezomib. Treatment with intravenous bortezomib is associated with an increased risk of developing peripheral neuropathy.

  10. 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

  11. 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

  12. Association between fine particulate matter exposure and subclinical atherosclerosis: A meta-analysis.

    PubMed

    Akintoye, Emmanuel; Shi, Liuhua; Obaitan, Itegbemie; Olusunmade, Mayowa; Wang, Yan; Newman, Jonathan D; Dodson, John A

    2016-04-01

    Epidemiological studies in humans that have evaluated the association between fine particulate matter (PM2.5) and atherosclerosis have yielded mixed results. In order to further investigate this relationship, we conducted a comprehensive search for studies published through May 2014 and performed a meta-analysis of all available observational studies that investigated the association between PM2.5 and three noninvasive measures of clinical and subclinical atherosclerosis: carotid intima media thickness, arterial calcification, and ankle-brachial index. Five reviewers selected studies based on predefined inclusion criteria. Pooled mean change estimates and 95% confidence intervals were calculated using random-effects models. Assessment of between-study heterogeneity was performed where the number of studies was adequate. Our pooled sample included 11,947 subjects for carotid intima media thickness estimates, 10,750 for arterial calcification estimates, and 6497 for ankle-brachial index estimates. Per 10 µg/m(3) increase in PM2.5 exposure, carotid intima media thickness increased by 22.52 µm but this did not reach statistical significance (p = 0.06). We did not find similar associations for arterial calcification (p = 0.44) or ankle-brachial index (p = 0.85). Our meta-analysis supports a relationship between PM2.5 and subclinical atherosclerosis measured by carotid intima media thickness. We did not find a similar relationship between PM2.5 and arterial calcification or ankle-brachial index, although the number of studies was small. © The European Society of Cardiology 2015.

  13. Mortality associated with anxiolytic and hypnotic drugs-A systematic review and meta-analysis.

    PubMed

    Parsaik, Ajay K; Mascarenhas, Soniya S; Khosh-Chashm, Darrow; Hashmi, Aqeel; John, Vineeth; Okusaga, Olaoluwa; Singh, Balwinder

    2016-06-01

    Use of hypnotics or anxiolytic drugs is common and various studies have reported increased mortality with hypnotics or anxiolytic use. To consolidate the evidence on mortality risk associated with hypnotics or anxiolytic use Major databases were searched through April 2014 for studies reporting mortality risk associated with hypnotics or anxiolytics use. A pooled hazard ratio with 95% confidence interval was estimated using random-effects model. After screening 2188 articles, 25 studies (24 cohort, 1 case-control) enrolling 2,350,093 patients with 59% females (age 18-102 years) were included in the meta-analysis. Hypnotics or anxiolytic users had 43% higher risk of mortality than non-users (hazard ratio, 1.43; 95% confidence interval, [1.12, 1.84]). Eight studies reported risk estimates for each gender category and pooled results from these studies showed increased risk of mortality among men (hazard ratio = 1.60, 95% confidence interval = [1.29,1.99]) and women (hazard ratio = 1.68, 95% confidence interval = [1.38, 2.04]). Pooled results from 10 studies showed higher mortality among benzodiazepine users compared to non-users (hazard ratio = 1.60, 95% confidence interval = [1.03, 2.49]), while pooled results from five studies showed an increased risk of mortality with Z-drugs use although the effect could not reach statistical significance (hazard ratio = 1.73, 95% confidence interval = [0.95, 3.16]). Significant heterogeneity was observed in the analyses and the quality of included studies was good. This meta-analysis suggests that hypnotics or anxiolytics drugs use is associated with increased mortality and hence should be used with caution. Future studies focused on underlying mechanism of increased mortality with hypnotics or anxiolytics use are required. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  14. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease.

    PubMed

    Siri-Tarino, Patty W; Sun, Qi; Hu, Frank B; Krauss, Ronald M

    2010-03-01

    A reduction in dietary saturated fat has generally been thought to improve cardiovascular health. The objective of this meta-analysis was to summarize the evidence related to the association of dietary saturated fat with risk of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD; CHD inclusive of stroke) in prospective epidemiologic studies. Twenty-one studies identified by searching MEDLINE and EMBASE databases and secondary referencing qualified for inclusion in this study. A random-effects model was used to derive composite relative risk estimates for CHD, stroke, and CVD. During 5-23 y of follow-up of 347,747 subjects, 11,006 developed CHD or stroke. Intake of saturated fat was not associated with an increased risk of CHD, stroke, or CVD. The pooled relative risk estimates that compared extreme quantiles of saturated fat intake were 1.07 (95% CI: 0.96, 1.19; P = 0.22) for CHD, 0.81 (95% CI: 0.62, 1.05; P = 0.11) for stroke, and 1.00 (95% CI: 0.89, 1.11; P = 0.95) for CVD. Consideration of age, sex, and study quality did not change the results. A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.

  15. Association of inorganic arsenic exposure with type 2 diabetes mellitus: a meta-analysis.

    PubMed

    Wang, Weijing; Xie, Zhutian; Lin, Yan; Zhang, Dongfeng

    2014-02-01

    The association of long-term effects of inorganic arsenic (iAs) exposure with type 2 diabetes mellitus (T2DM) risk remains controversial. A literature search was performed in PubMed, China National Knowledge Infrastructure and Web of Knowledge for relevant available articles published in English or Chinese from 1 January 1990 to 5 June 2013. Case-control, cohort or cross-sectional studies evaluating iAs and T2DM were included. The DerSimonian and Laird random effect model was adopted as the pooling method. Dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. Of the 569 articles identified through searching databases, 17 published articles with 2,243,745 participants for iAs in drinking water and 21 083 participants for total arsenic (tAs) in urine were included for this meta-analysis. The pooled relative risk with 95% CI of T2DM for the highest versus lowest category of iAs exposure level in drinking water was 1.75 (1.20 to 2.54). After removing three studies that had a strong effect on heterogeneity, the pooled relative risk was 1.23 (1.12 to 1.36). Dose-response analysis suggested T2DM risk increased by 13% (1.13 (1.00 to 1.27)) for every 100 µg/L increment of iAs in drinking water. Significant association of T2DM risk with tAs in urine was also found 1.28 (1.14 to 1.44). This meta-analysis indicates that long-term iAs exposure might be positively associated with T2DM risk.

  16. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis.

    PubMed

    Corona, Giovanni; Rastrelli, Giulia; Monami, Matteo; Saad, Farid; Luconi, Michaela; Lucchese, Marcello; Facchiano, Enrico; Sforza, Alessandra; Forti, Gianni; Mannucci, Edoardo; Maggi, Mario

    2013-06-01

    Few randomized clinical studies have evaluated the impact of diet and physical activity on testosterone levels in obese men with conflicting results. Conversely, studies on bariatric surgery in men generally have shown an increase in testosterone levels. The aim of this study is to perform a systematic review and meta-analysis of available trials on the effect of body weight loss on sex hormones levels. Meta-analysis. An extensive Medline search was performed including the following words: 'testosterone', 'diet', 'weight loss', 'bariatric surgery', and 'males'. The search was restricted to data from January 1, 1969 up to August 31, 2012. Out of 266 retrieved articles, 24 were included in the study. Of the latter, 22 evaluated the effect of diet or bariatric surgery, whereas two compared diet and bariatric surgery. Overall, both a low-calorie diet and bariatric surgery are associated with a significant (P<0.0001) increase in plasma sex hormone-binding globulin-bound and -unbound testosterone levels (total testosterone (TT)), with bariatric surgery being more effective in comparison with the low-calorie diet (TT increase: 8.73 (6.51-10.95) vs 2.87 (1.68-4.07) for bariatric surgery and the low-calorie diet, respectively; both P<0.0001 vs baseline). Androgen rise is greater in those patients who lose more weight as well as in younger, non-diabetic subjects with a greater degree of obesity. Body weight loss is also associated with a decrease in estradiol and an increase in gonadotropins levels. Multiple regression analysis shows that the degree of body weight loss is the best determinant of TT rise (B=2.50±0.98, P=0.029). These data show that weight loss is associated with an increase in both bound and unbound testosterone levels. The normalization of sex hormones induced by body weight loss is a possible mechanism contributing to the beneficial effects of surgery in morbid obesity.

  17. Association Between Psychological Distress and Liver Disease Mortality: A Meta-analysis of Individual Study Participants.

    PubMed

    Russ, Tom C; Kivimäki, Mika; Morling, Joanne R; Starr, John M; Stamatakis, Emmanuel; Batty, G David

    2015-05-01

    Risk factors for cardiovascular disease, such as obesity and hypertension, have been associated with nonalcoholic fatty liver disease. Psychological distress (symptoms of anxiety and depression) is a risk factor for cardiovascular disease, so it might also be associated, directly or indirectly, with liver disease. We investigated the relationship between psychological distress (measured by the 12-item General Health Questionnaire [GHQ]) and liver disease mortality. We performed a meta-analysis of data from individual participants in 16 prospective studies of the general population in the United Kingdom, initiated from 1994 through 2008. Subjects were assigned to groups based on GHQ score: 0 (no distress), 1-3, 4-6, or 7-12. We analyzed data from 166,631 individuals (55% women; mean ± SD age, 46.6 ± 18.4 years; range, 16-102 years). During a mean follow-up period of 9.5 years, 17,368 participants died (457 with liver disease). We found a significant increase in liver disease mortality with increase in GHQ score (Ptrend < .001). The age- and sex-adjusted hazard ratio for the highest GHQ score category (ie, 7-12), compared with the 0 score category, was 3.48 (95% confidence interval: 2.68-4.52). After adjustment for health behaviors, socioeconomic status, body mass index, and diabetes, this hazard ratio decreased to 2.59 (95% confidence interval: 1.82-3.68). Based on a meta-analysis, psychological distress is associated with liver disease mortality, although this finding requires additional analysis. Although one is not likely to cause the other, we provide additional evidence for the deleterious effects of psychological problems on physical health. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. 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

  19. 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.

  20. 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

  1. 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.

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

    PubMed Central

    Subirana, Isaac; González, Juan R

    2014-01-01

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

  3. 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

  4. Exploring association between statin use and breast cancer risk: an updated meta-analysis.

    PubMed

    Islam, Md Mohaimenul; Yang, Hsuan-Chia; Nguyen, Phung-Anh; Poly, Tahmina Nasrin; Huang, Chih-Wei; Kekade, Shwetambara; Khalfan, Abdulwahed Mohammed; Debnath, Tonmoy; Li, Yu-Chuan Jack; Abdul, Shabbir Syed

    2017-09-22

    The benefits of statin treatment for preventing cardiac disease are well established. However, preclinical studies suggested that statins may influence mammary cancer growth, but the clinical evidence is still inconsistent. We, therefore, performed an updated meta-analysis to provide a precise estimate of the risk of breast cancer in individuals undergoing statin therapy. For this meta-analysis, we searched PubMed, the Cochrane Library, Web of Science, Embase, and CINAHL for published studies up to January 31, 2017. Articles were included if they (1) were published in English; (2) had an observational study design with individual-level exposure and outcome data, examined the effect of statin therapy, and reported the incidence of breast cancer; and (3) reported estimates of either the relative risk, odds ratios, or hazard ratios with 95% confidence intervals (CIs). We used random-effect models to pool the estimates. Of 2754 unique abstracts, 39 were selected for full-text review, and 36 studies reporting on 121,399 patients met all inclusion criteria. The overall pooled risks of breast cancer in patients using statins were 0.94 (95% CI 0.86-1.03) in random-effect models with significant heterogeneity between estimates (I (2) = 83.79%, p = 0.0001). However, we also stratified by region, the duration of statin therapy, methodological design, statin properties, and individual stain use. Our results suggest that there is no association between statin use and breast cancer risk. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or the result of some unmeasured confounding variable. Therefore, more research is needed.

  5. 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.

  6. 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.

  7. 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

  8. Association of urinary cadmium with risk of diabetes: a meta-analysis.

    PubMed

    Li, Yujie; Zhang, Yun; Wang, Weijing; Wu, Yili

    2017-04-01

    The association between urinary cadmium and diabetes risk remains controversial. PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang Data updated on 21 June 2016 were searched for eligible publications. Pooled odds ratio (OR) with 95% confidence interval (CI) of diabetes for highest versus lowest level of urinary cadmium was calculated by using fixed-effect model or random-effect model. Dose-response relationship between urinary cadmium and diabetes was estimated by restricted cubic spline. A total of nine studies with 28,691 participants were included in this meta-analysis. The pooled OR of diabetes for the highest versus lowest level of urinary cadmium was 1.02 (95% CI, 1.00, 1.05; I (2) = 42.3%). In subgroup analysis, the ORs were 1.02 (95% CI 1.00, 1.05; I (2) = 0.9%) for studies conducted in Asia and 1.11 (95% CI 0.88, 1.41; I (2) = 86.3%) in America. For dose-response analysis, a linear relationship was found between urinary cadmium and the risk of diabetes (P for nonlinear = 0.5856). For every l μg/g creatinine increment of urinary cadmium, the risk of diabetes increased by 16% (1.16, 95% CI 1.08, 1.25). This meta-analysis suggests that cadmium exposure might be significantly associated with prevalence of diabetes, but large prospective studies are needed to confirm this finding.

  9. 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

  10. 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

  11. Association between type 1 diabetes mellitus and risk of epilepsy: A meta-analysis of observational studies.

    PubMed

    Yan, Dandan; Zhao, Enfa; Zhang, Hong; Luo, Xiaohui; Du, Yajuan

    2017-01-01

    A potential association between type 1 diabetes mellitus and subsequent epilepsy emerged in recent studies. This study aimed to evaluate the possible relationship between type 1 diabetes mellitus and epilepsy using meta-analysis. Pubmed, ISI Web of Knowledge, Embase and Cochrane Library were searched for potential studies of the association between type 1 diabetes mellitus and epilepsy from inception to February 1, 2017. Two investigators independently screened studies for inclusion and extracted related data; discrepancies were solved by consensus. Random effects model of Hazard Ratio (HR) was used to estimate the strength of association. We identified 13 papers from potentially relevant articles of which 3 cohort studies met the inclusion criteria. Random effects meta-analysis showed that type 1 diabetes mellitus was associated with an increased risk of epilepsy with HR = 3.29 (95% CI: 2.61-4.14; I(2) = 0, p = 0.689). Similar results were observed in type 1 diabetes mellitus patents younger than 18-years-old with HR = 2.96 (95% CI: 2.28-3.84; I(2) = 0, p = 0.571). Meta-analysis of 2 studies that adjusted for potential confounders yielded an increased risk of epilepsy with HR = 2.89 (95% CI: 2.26-3.70; I(2) = 0, p = 0.831). The meta-analysis indicates that type 1 diabetes mellitus is associated with a statistically significant increased risk for epilepsy compared to those without type 1 diabetes mellitus.

  12. 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.

  13. 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

  14. 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.…

  15. Pathologic Markers in Surgically Treated HPV-Associated Oropharyngeal Cancer: Retrospective Study, Systematic Review, and Meta-analysis.

    PubMed

    Tassone, Patrick; Crawley, Meghan; Bovenzi, Cory; Zhan, Tingting; Keane, William; Cognetti, David; Luginbuhl, Adam; Curry, Joseph

    2017-05-01

    Human papillomavirus-associated (HPV) oropharyngeal cancer is a unique clinical entity whose incidence is increasing. It is controversial whether traditional pathologic markers of aggressive head and neck cancer also apply in surgically treated HPV-associated disease. Retrospective study, systematic review, and meta-analysis Data Sources: PubMed and Cochrane review. PubMed and Cochrane review were searched for published articles on surgically treated HPV-associated oropharyngeal cancer. Eligible studies were included in a meta-analysis of survival using several clinicopathologic markers as predictors. Surgically treated HPV-positive oropharyngeal cancer patients at our institution were studied retrospectively and added to the meta-analysis. Eight published reports, plus our retrospective series, were included in the meta-analysis. This showed significant impact on event-free survival for T stage, nodal number, perineural invasion, and lymphovascular invasion (all P < .05) but not for N stage extracapsular extension ( P = ns). While many traditional clinico-pathologic markers of aggressive disease in head and neck cancer also impact survival in surgically treated HPV-associated oropharyngeal cancer, extracapsular extension may be less important.

  16. 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.…

  17. 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

  18. Association between hypertension and risk of knee osteoarthritis: A meta-analysis of observational studies.

    PubMed

    Zhang, Yi-Min; Wang, Jun; Liu, Xiao-Guang

    2017-08-01

    Evidence from observational studies shows that hypertension may be a risk factor for knee osteoarthritis (OA). However, the relationship between hypertension and knee OA risk remains controversial. This study aimed to quantitatively assess the relationship between hypertension and risk of knee OA.Three electronic databases (PubMed, Embase, and Cochrane Library) were searched up to July 25, 2016. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were extracted from the included observational studies. Publication bias, heterogeneity test, and subgroup analyses were performed.Eight studies including 2 cohort studies and 6 cross-sectional studies with 9762 participants were finally included in this meta-analysis. The results showed that hypertension was significantly associated with higher radiographic knee OA and symptomatic knee OA risks of 2.01 (95% CI, 1.28-3.15, I = 90.2%, P for heterogeneity <.001) and 1.49 (95% CI, 1.26-1.77, I = 0%, P for heterogeneity <.412), respectively. No publication bias was detected. The subgroup analysis showed that the study design did not influence the results (radiographic knee OA: OR = 1.42, 95% CI, 1.19-1.71 for cross-sectional studies and OR = 2.17, 95% CI, 1.30-3.63 for cohort studies; and symptomatic knee OA: OR = 1.85, 95% CI, 1.10-3.13) for cross-sectional studies and OR = 2.74, 95% CI, 1.81-4.16 for cohort studies).This meta-analysis showed that there was a significant relationship between hypertension and knee OA (both radiographic and symptomatic). However, further original studies are needed that use a better design.

  19. Lowered circulating apelin is significantly associated with an increased risk for hypertension: A meta-analysis.

    PubMed

    Xie, Hong; Luo, Gaoqing; Zheng, Yong; Hu, Dan; Peng, Feng; Xie, Liangdi

    2017-01-01

    Apelin is a bioactive peptide manifesting a potent vasodilatory property. In this meta-analysis, we aimed to investigate for the first time whether circulating apelin differed significantly between hypertensive patients and normotensive controls. Both PubMed and Embase were searched for eligible articles. Eligibility evaluation and data collection were done independently by two investigators. Weighted mean difference (WMD) with 95% confidence interval (CI) was calculated under random-effects model by STATA. Ten studies were synthesized finally, including 1610 patients and 1105 controls. Overall analysis revealed that circulating apelin was significantly lowered in patients than in controls (WMD = -39.85 pg/mL, 95% CI: -65.56 to -14.15; P = 0.002), with significant heterogeneity (I(2) = 89.4%). By race, patients had lower circulating apelin than controls in Caucasian populations (WMD = -79.82 pg/mL, 95% CI: -105.80 to -53.85; P < 0.001), without heterogeneity (I(2)=0.0%), while no significance was observed in Chinese and African-Americans. Further grouping studies by source of controls found a significant reduction in circulating apelin in studies with hospital-based controls (WMD = -96.28 pg/mL, 95% CI: -129.67 to -62.88; P < 0.001) (I(2) = 49.4%), but not in studies with population-based controls. Via a meta-analysis of 10 studies and on 2715 subjects, our findings demonstrated that lowered circulating apelin was significantly associated with an increased risk for hypertension, especially in Caucasian populations.

  20. 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.

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

    PubMed Central

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

    2013-01-01

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

  2. Association between interferon-γ +874 T/A polymorphism and susceptibility to autoimmune diseases: a meta-analysis.

    PubMed

    Lee, Y H; Bae, S-C

    2016-06-01

    The aim of this study was to explore whether the interferon (IFN)-γ +874 T/A polymorphism plays a role in modifying the risk of autoimmune diseases. A meta-analysis was conducted on the association between the IFN-γ +874 T/A polymorphism and autoimmune diseases. Eighteen studies with a total of 2952 patients and 3832 controls were included in the meta-analysis. The meta-analysis revealed no association between autoimmune diseases and the IFN-γ +874 T allele in all study subjects (odds ratio (OR)=1.023, 95% confidence interval (CI) = 0.894-1.171, p = 0.738), but stratification by ethnicity indicated an association between the IFN-γ +874 T allele and autoimmune diseases in Latin American subjects (OR = 0.780, 95% CI = 0.629-0.953, p = 0.015). Meta-analysis also revealed an association between autoimmune diseases and the IFN-γ +874 T/A polymorphism in Caucasian and Middle Eastern subjects under a dominant inheritance model (OR = 0.686, 95% CI = 0.489-0.964, p = 0.003; OR = 1.414, 95% CI = 1.102-1.813, p = 0.006). Meta-analysis by autoimmune disease type indicated an association between ITP and the IFN-γ +874 T allele (OR = 1.753, 95% CI = 1.228-2.503, p = 0.002), but not for vasculitis, vitiligo, and auto-immune thyroid disease. Meta-analysis also showed a significant association between the IFN-γ +874 T/A polymorphism and systemic lupus erythematosus (SLE) under the dominant model (OR = 1.668, 95% CI = 1.114-2.497, p = 0.013). This meta-analysis indicates that the IFN-γ +874 T/A polymorphism may play a significant role in modifying the risk of autoimmune diseases in Caucasian, Latin American, and Middle Eastern subjects, and in particular shows that the IFN-γ +874 T/A polymorphism is associated with increased genetic susceptibility to idiopathic thrombocytopenic purpura and SLE. © The Author(s) 2015.

  3. 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

  4. Genome-Wide Association Studies of Pigmentation and Skin Cancer: A Review and Meta-Analysis

    PubMed Central

    Gerstenblith, MR; Shi, J; Landi, MT

    2011-01-01

    Summary Recent genome-wide association studies (GWAS) identified genetic loci associated with pigmentation, nevi, and skin cancer. We performed a review and meta-analysis of GWAS results, grouping them into four categories: (1) loci associated with pigmentation (hair, eye and/or skin color), cutaneous UV-response (sun sensitivity and/or freckling), and skin cancer; (2) loci associated with nevi and melanoma; (3) loci associated with pigmentation and/or cutaneous UV-response, but not skin cancer; and (4) loci distinctly associated with skin cancer, mostly basal cell carcinoma (BCC), but not pigmentation or cutaneous UV-response. These findings suggest at least two pathways for melanoma development (via pigmentation and via nevi), and two pathways for BCC development (via pigmentation and independent of pigmentation). However, further work is necessary to separate the association with skin cancer from the association with pigmentation. As with any GWAS, the identified loci may not include the causal variants and need confirmation by direct genome sequencing. PMID:20546537

  5. Genome-wide association studies of pigmentation and skin cancer: a review and meta-analysis.

    PubMed

    Gerstenblith, Meg R; Shi, Jianxin; Landi, Maria Teresa

    2010-10-01

    Recent genome-wide association studies (GWAS) identified genetic loci associated with pigmentation, nevi, and skin cancer. We performed a review and meta-analysis of GWAS results, grouping them into four categories: (i) loci associated with pigmentation (hair, eye, and/or skin color), cutaneous UV-response (sun sensitivity and/or freckling), and skin cancer; (ii) loci associated with nevi and melanoma; (iii) loci associated with pigmentation and/or cutaneous UV-response but not skin cancer; and (iv) loci associated distinctly with skin cancer, mostly basal cell carcinoma, but not pigmentation or cutaneous UV-response. These findings suggest at least two pathways for melanoma development (via pigmentation and via nevi), and two pathways for basal cell carcinoma development (via pigmentation and independent of pigmentation). However, further work is necessary to separate the association with skin cancer from the association with pigmentation. As with any GWAS, the identified loci may not include the causal variants and may need confirmation by direct genome sequencing.

  6. Association between allergic conditions and risk of prostate cancer: A Prisma-Compliant Systematic Review and Meta-Analysis.

    PubMed

    Zhu, Jianguo; Song, Jukun; Liu, Zezhen; Han, Jin; Luo, Heng; Liu, Yunlin; Jia, Zhenyu; Dong, Yuanbo; Zhang, Wei; Jiang, Funeng; Wu, Chinlee; Sun, Zaolin; Zhong, Weide

    2016-10-21

    Association between allergic conditions and prostate cancer risk has been investigated for many years. However, the results from available evidence for the association are inconsistent. We conducted a meta-analysis to evaluate the relationship between allergic conditions (asthma, atopy, hay fever and "any allergy") and risk of prostate cancer. The PubMed and Embase databases were searched to screen observational studies meeting our meta-analysis criteria. Study selection and data extraction from included studies were independently performed by two authors. Twenty studies were considered eligible involving 5 case-control studies and 15 cohort studies. The summary relative risk (RR) for developing prostate cancer risk was 1.04 (95%CI: 0.92-1.17) for asthma, and 1.25 (95%CI: 0.74-2.10) for atopy, 1.04 (95%CI: 0.99-1.09) for hay fever, 0.96 (95%CI: 0.86-1.06) for any allergy. In the Subgroup and sensitivity analysis, similar results were produced. Little evidence of publication bias was observed. The present meta-analysis of observational studies indicates that no indication of an association between allergic conditions and risk of prostate cancer was found, and the meta-analysis does not support neither the original hypothesis of an overall cancer protective effect of allergic conditions, nor that of an opposite effect in the development of prostate cancer.

  7. Meta-analysis of the Association Between Variants in SORL1 and Alzheimer Disease

    PubMed Central

    Reitz, Christiane; Cheng, Rong; Rogaeva, Ekaterina; Lee, Joseph H.; Tokuhiro, Shinya; Zou, Fanggeng; Bettens, Karolien; Sleegers, Kristel; Tan, Eng King; Kimura, Ryo; Shibata, Nobuto; Arai, Heii; Kamboh, M. Ilyas; Prince, Jonathan A.; Maier, Wolfgang; Riemenschneider, Matthias; Owen, Michael; Harold, Denise; Hollingworth, Paul; Cellini, Elena; Sorbi, Sandro; Nacmias, Benedetta; Takeda, Masatoshi; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Younkin, Steven; Williams, Julie; van Broeckhoven, Christine; Farrer, Lindsay A.; St George–Hyslop, Peter H.; Mayeux, Richard

    2011-01-01

    Objective To reexamine the association between the neuronal sortilin-related receptor gene (SORL1) and Alzheimer disease (AD). Design Comprehensive and unbiased meta-analysis of all published and unpublished data from case-control studies for the SORL1 single-nucleotide polymorphisms (SNPs) that had been repeatedly assessed across studies. Setting Academic research institutions in the United States, the Netherlands, Canada, Belgium, the United Kingdom, Singapore, Japan, Sweden, Germany, France, and Italy. Participants All published white and Asian case-control data sets, which included a total of 12 464 cases and 17 929 controls. Main Outcome Measures Alzheimer disease according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (now known as the Alzheimer’s Association). Results In the white data sets, several markers were associated with AD after correction for multiple testing, including previously reported SNPs 8, 9, and 10 (P<.001). In addition, the C-G-C haplotype at SNPs 8 through 10 was associated with AD risk (P<.001). In the combined Asian data sets, SNPs 19 and 23 through 25 were associated with AD risk (P<.001). The disease-associated alleles at SNPs 8, 9, and 10 (120 873 131-120 886 175 base pairs [bp]; C-G-C alleles), at SNP 19 (120 953 300 bp; G allele), and at SNPs 24 through 25 (120 988 611 bp; T and C alleles) were the same previously reported alleles. The SNPs 4 through 5, 8 through 10, 12, and 19 through 25 belong to distinct linkage disequilibrium blocks. The same alleles at SNPs 8 through 10 (C-G-C), 19 (G), and 24 and 25 (T and C) have also been associated with AD endophenotypes, including white matter hyperintensities and hippocampal atrophy on magnetic resonance imaging, cerebrospinal fluid measures of amyloid β-peptide 42, and full-length SORL1 expression in the

  8. Association between interleukin-6 polymorphisms and urinary system cancer risk: evidence from a meta-analysis

    PubMed Central

    Zhang, Kaiping; Zhang, Li; Zhou, Jun; Hao, Zongyao; Fan, Song; Yang, Cheng; Liang, Chaozhao

    2016-01-01

    Background Interleukin-6 (IL-6) is a multifunctional proinflammatory cytokine involved in cancer initiation and progression. Numerous studies have investigated the associations between IL-6 polymorphisms (IL-6 −174G>C, −592G>C, −597G>A) and risk of urinary system cancers, including prostate cancer, bladder cancer, and renal cell cancer. However, conclusions from these studies were controversial. Thus, we conducted the current meta-analysis to obtain the comprehensive profile regarding the association between IL-6 polymorphisms and urinary system cancer risk. Methods According to inclusion and exclusion criteria, the associations of IL-6 polymorphisms with urinary system cancer were searched from database and analyzed using STATA 12.0 statistical software. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. Results A total of 20 previous publications consisting of 15,033 cases and 17,655 controls were involved in this meta-analysis. Significant association was observed in overall population regarding IL-6 −592G>C polymorphisms (G vs C: OR =0.1.30, 95% CI =1.13−2.52; GG vs CC: OR =1.81, 95% CI =1.31−2.52; GG vs GC + CC: OR =1.33, 95% CI =1.02−1.75; GG + GC vs CC: OR =1.41, 95% CI =1.09−1.83). In the stratified analyses by ethnicity, the significant associations were found among Asian (GG vs CC: OR =1.89, 95% CI =1.34−2.66; GG + GC vs CC: OR =1.43, 95% CI =1.09−1.87) and Black population (GC vs CC: OR =0.20, 95% CI =0.05−0.82) rather than Caucasian men. Likewise, there were noticeable associations in almost all the other subanalyses such as cancer types, control sources, genotyped methods, and sample sizes. However, no significant associations were identified between any of IL-6 −174G>C polymorphisms with urinary system cancer, except for Asian population (G vs C: OR =0.81, 95% CI =0.70−0.95; GG vs CC: OR =0.51, 95% CI =0.35−0.74; GC vs CC: OR =0.49, 95% CI =0.33−0.72; GG + GC vs CC

  9. Association between interleukin-6 polymorphisms and urinary system cancer risk: evidence from a meta-analysis.

    PubMed

    Zhang, Kaiping; Zhang, Li; Zhou, Jun; Hao, Zongyao; Fan, Song; Yang, Cheng; Liang, Chaozhao

    2016-01-01

    Interleukin-6 (IL-6) is a multifunctional proinflammatory cytokine involved in cancer initiation and progression. Numerous studies have investigated the associations between IL-6 polymorphisms (IL-6 -174G>C, -592G>C, -597G>A) and risk of urinary system cancers, including prostate cancer, bladder cancer, and renal cell cancer. However, conclusions from these studies were controversial. Thus, we conducted the current meta-analysis to obtain the comprehensive profile regarding the association between IL-6 polymorphisms and urinary system cancer risk. According to inclusion and exclusion criteria, the associations of IL-6 polymorphisms with urinary system cancer were searched from database and analyzed using STATA 12.0 statistical software. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. A total of 20 previous publications consisting of 15,033 cases and 17,655 controls were involved in this meta-analysis. Significant association was observed in overall population regarding IL-6 -592G>C polymorphisms (G vs C: OR =0.1.30, 95% CI =1.13-2.52; GG vs CC: OR =1.81, 95% CI =1.31-2.52; GG vs GC + CC: OR =1.33, 95% CI =1.02-1.75; GG + GC vs CC: OR =1.41, 95% CI =1.09-1.83). In the stratified analyses by ethnicity, the significant associations were found among Asian (GG vs CC: OR =1.89, 95% CI =1.34-2.66; GG + GC vs CC: OR =1.43, 95% CI =1.09-1.87) and Black population (GC vs CC: OR =0.20, 95% CI =0.05-0.82) rather than Caucasian men. Likewise, there were noticeable associations in almost all the other subanalyses such as cancer types, control sources, genotyped methods, and sample sizes. However, no significant associations were identified between any of IL-6 -174G>C polymorphisms with urinary system cancer, except for Asian population (G vs C: OR =0.81, 95% CI =0.70-0.95; GG vs CC: OR =0.51, 95% CI =0.35-0.74; GC vs CC: OR =0.49, 95% CI =0.33-0.72; GG + GC vs CC: OR =0.50, 95% CI =0.35-0.72; respectively). In addition

  10. 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.

  11. Quantitative Assessment of the Association between ABC Polymorphisms and Osteosarcoma Response: a Meta-analysis.

    PubMed

    Chen, Xu; Jiang, Min; Zhao, Rui-Ke; Gu, Guo-Hao

    2015-01-01

    ABC proteins are one key type of transport superfamilies which undertake majority of drug transport, which affect the osteosarcoma response to chemotherapeutics. Previous studies have suggested the association between ABC polymorphisms and osteosarcoma response. However, the results of previous studies remain controversial. Therefore, we perform a meta-analysis to get a more precise estimation of this association. The association between ABC polymorphisms and osteosarcoma response was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Three polymorphisms of ABC including ABCB1 rs1128503, ABCC3 rs4148416 and ABCC2 rs717620 polymorphism were investigated. Overall, significant association was observed between ABCC3 rs4148416 polymorphism and osteosarcoma response under allele contrast (T vs. C: OR=1.73, 95%CI=1.09-2.74, P=0.019), homozygote comparison (TT vs. CC: OR=2.00, 95%CI=1.25-3.23, P=0.004), recessive genetic model (TT vs. OR=1.80, 95%CI=1.14-2.84, P=0.011) and dominant genetic model (TT/TC vs. CC: OR=1.70, 95%CI=1.20-2.42, P=0.003). Moreover, significant association was also observed in Caucasian population rather than Asian population for ABCB1 rs1128503 polymorphism. We conclude that ABCC3 rs4148416 polymorphism was significantly associated with poor osteosarcoma response and ABCB1 rs1128503 polymorphism was significantly associated with good osteosarcoma response in Caucasian population rather than Asian population.

  12. 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

  13. Association of interleukin-10 gene promoter polymorphisms with recurrent pregnancy loss: a meta-analysis.

    PubMed

    Gu, Chongjuan; Gong, Hongxia; Zhang, Zheng; Yang, Zhao; Ma, Yongxin

    2016-07-01

    It has been reported single-nucleotide polymorphisms (SNPs) of the IL-10 promoter might be associated with the susceptibility to recurrent pregnancy loss (RPL). Owing to the inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the IL-10 promoter SNPs and RPL risk. A systematic search of studies on the association of the three SNPs with RPL was conducted in PubMed and Embase. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to pool the effect size. Eleven case-control studies on rs1800896, seven studies on rs1800871, and eight studies on rs1800872 were included. A significant association was identified between IL-10 rs1800896 with RPL risk (G versus A: OR = 1.21, 95 % CI 1.09-1.35). No evidence of association was found between rs1800871 and RPL when restricted to those studies in Hardy-Weinberg equilibrium in controls (T versus C: OR = 1.25, 95 % CI 0.76-2.06). No statistical association was demonstrated between rs1800872 and RPL (C versus A: OR = 1.08, 95 % CI 0.83-1.42). IL-10 rs1800896 significantly increases the risk of RPL, while rs1800872 is not correlated with RPL risk. No significant association is demonstrated between rs1800871 and RPL risk but this requires further investigation.

  14. 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

  15. A Review of Genetic Association Studies of Obstructive Sleep Apnea: Field Synopsis and Meta-Analysis

    PubMed Central

    Varvarigou, Vasileia; Dahabreh, Issa J.; Malhotra, Atul; Kales, Stefanos N.

    2011-01-01

    Study Objectives: Obstructive sleep apnea (OSA) is a multifactorial disorder with a heritable component. We performed a field synopsis of genetic association studies of OSA to synthesize the available evidence. Design: Systematic literature review and meta-analysis. Setting: Genetic association studies. Patients or Participants: We searched multiple databases to identify studies of non-HLA genetic associations in OSA. We assessed the power of the primary studies to identify odds ratios (OR) in a plausible range and performed random effects meta-analyses for genetic associations investigated by at least 3 studies. We explored the consistency of the findings between population- and family-based studies. Interventions: None Measurements and Results: We identified a total of 31 population-based case-control studies reporting allele-frequency data on 48 polymorphism-OSA associations. Sample sizes were generally small (median number of cases = 102, 25th-75th percentile = 55-151; median number of controls = 79, 25th-75th percentile = 58-137), and genetic effects were moderate in magnitude (median OR = 1.15, 25th-75th percentile = 0.89-1.40). Studies were severely underpowered to detect ORs as high as 2; only eight comparisons (in 6 studies) had more than 90% power to identify a genetic effect of that magnitude at its current sample size. Four genetic associations had been investigated in ≥ 3 studies: TNFA (-308 A/G) rs1800629, ACE I/D, APOE ε2, and APOE ε4. Only TNFA rs1800629 was significantly associated with OSA under an allele frequency model (3 studies, odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.26-2.61). These results were robust to alternative genetic models; findings for APOE variants were consistent with those from family-based studies. Conclusions: The developing field of OSA genetics is currently dominated by small and underpowered investigations. Promising findings regarding TNFA rs1800629 need to be replicated in larger studies using more

  16. 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

    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

    2011-08-01

    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. 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. 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. 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.

  17. 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

  18. Pharmacogenetic Associations of Antipsychotic Drug-Related Weight Gain: A Systematic Review and Meta-analysis.

    PubMed

    Zhang, Jian-Ping; Lencz, Todd; Zhang, Ryan X; Nitta, Masahiro; Maayan, Lawrence; John, Majnu; Robinson, Delbert G; Fleischhacker, W Wolfgang; Kahn, Rene S; Ophoff, Roel A; Kane, John M; Malhotra, Anil K; Correll, Christoph U

    2016-11-01

    Although weight gain is a serious but variable adverse effect of antipsychotics that has genetic underpinnings, a comprehensive meta-analysis of pharmacogenetics of antipsychotic-related weight gain is missing. In this review, random effects meta-analyses were conducted for dominant and recessive models on associations of specific single nucleotide polymorphisms (SNP) with prospectively assessed antipsychotic-related weight or body mass index (BMI) changes (primary outcome), or categorical increases in weight or BMI (≥7%; secondary outcome). Published studies, identified via systematic database search (last search: December 31, 2014), plus 3 additional cohorts, including 222 antipsychotic-naïve youth, and 81 and 141 first-episode schizophrenia adults, each with patient-level data at 3 or 4 months treatment, were meta-analyzed. Altogether, 72 articles reporting on 46 non-duplicated samples (n = 6700, mean follow-up = 25.1wk) with 38 SNPs from 20 genes/genomic regions were meta-analyzed (for each meta-analysis, studies = 2-20, n = 81-2082). Eleven SNPs from 8 genes were significantly associated with weight or BMI change, and 4 SNPs from 2 genes were significantly associated with categorical weight or BMI increase. Combined, 13 SNPs from 9 genes (Adrenoceptor Alpha-2A [ADRA2A], Adrenoceptor Beta 3 [ADRB3], Brain-Derived Neurotrophic Factor [BDNF], Dopamine Receptor D2 [DRD2], Guanine Nucleotide Binding Protein [GNB3], 5-Hydroxytryptamine (Serotonin) Receptor 2C [HTR2C], Insulin-induced gene 2 [INSIG2], Melanocortin-4 Receptor [MC4R], and Synaptosomal-associated protein, 25kDa [SNAP25]) were significantly associated with antipsychotic-related weight gain (P-values < .05-.001). SNPs in ADRA2A, DRD2, HTR2C, and MC4R had the largest effect sizes (Hedges' g's = 0.30-0.80, ORs = 1.47-1.96). Less prior antipsychotic exposure (pediatric or first episode patients) and short follow-up (1-2 mo) were associated with larger effect sizes. Individual antipsychotics did not

  19. 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.

  20. 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

  1. 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

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

    NASA Astrophysics Data System (ADS)

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

    2011-04-01

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

  3. 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.

  4. 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

  5. Meta-analysis of association between rs1447295 polymorphism and prostate cancer susceptibility.

    PubMed

    Zhou, Juan; Yu, Yang; Zhu, Anyou; Wang, Fengchao; Kang, Shuxia; Pei, Yunfeng; Cao, Chunping; Ding, Chen; Wang, Duping; Sun, Li; Niu, Guoping

    2017-09-15

    A number of studies have found that the single nucleotide polymorphisms (SNPs) within the 8q24 region of genome were associated with the susceptibility of prostate cancer. Association between 8q24 SNP variant rs1447295 and higher risk of prostate cancer had been investigated, but those studies were incomplete and the conclusions were obscure. To better elucidate the relationship between rs1447295 polymorphism and the susceptibility of prostate cancer, we performed a more comprehensive meta-analysis about the association between rs1447295 polymorphism and prostate cancer susceptibility by collecting relevant articles published up to November, 2016 and excluding many replicated cohort data existing in previous reports, which made the conclusion more reliant and objective. The results showed that there was a significant prostate cancer risk associated with rs1447295 polymorphism not only in the total groups, but also in American, European and Asian descent subgroups. Meanwhile, a comprehensive analysis about the association between rs1447295 polymorphism and prostate cancer risk were conducted by using different clinical characteristic stratifications including Gleason score, tumor stage and PSA level. The result showed that rs1447295 polymorphism was correlated with different stages of prostate cancer. There are strong association between rs1447295 polymorphism and prostate cancer susceptibility in different ethnic groups and different prostate cancer stage, suggesting that rs1447295 might serve as a reliable biomarker for prostate cancer diagnosis.

  6. 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.

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

    PubMed

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

    2016-01-01

    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. 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. 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. 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.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

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

    PubMed Central

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

    2014-01-01

    Background. Although individual metabolic risk factors are reported to be associated with breast cancer risk, controversy surrounds risk of breast cancer from metabolic syndrome (MS). We report the first systematic review and meta-analysis of the association between MS and breast cancer risk in all adult females. Methods. Studies were retrieved by searching four electronic reference databases [PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and ProQuest through June 30, 2012] and cross-referencing retrieved articles. Eligible for inclusion were longitudinal studies reporting associations between MS and breast cancer risk among females aged 18 years and older. Relative risks and 95% confidence intervals were calculated for each study and pooled using random-effects models. Publication bias was assessed quantitatively (Trim and Fill) and qualitatively (funnel plots). Heterogeneity was examined using Q and 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. PMID:25653879

  15. 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.

  16. The association between gout and cataract risk: A meta-analysis.

    PubMed

    Luo, Chenqi; Chen, Xinyi; Jin, Hongchuan; Yao, Ke

    2017-01-01

    To evaluate the relationship between gout and age-related cataracts (ARCs). A comprehensive literature search of the PubMed and Web of Science databases was conducted to identify papers on the association between gout and cataract risk that had been published between February 1991 and January 2017. Pooled relative risks (RRs) or odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated. The random-effects model was used instead of the fixed-effects model when heterogeneity was identified, as indicated by a Cochran's Q statistic P-value <0.10 or I2 index score >50%. A total of 3 cross-sectional studies and 3 case-control studies were included in the meta-analysis. Gout was significantly associated with increased odds of ARCs (OR 1.53, 95% CI 1.27-1.84). In the subgroup analysis, gout exhibited positive associations with the odds of posterior subcapsular cataracts (PSCs, OR 1.69, 95% CI: 1.06-2.70) and cortical cataracts (CCs, OR 1.39, 95% CI: 1.06-1.81). However, no association was identified between gout and the odds of nuclear cataracts. The current literature suggested that gout may be associated with increased odds of ARCs, especially PSCs and CCs. Further efforts should be made to confirm these findings and clarify the effect of gout and gout medications on the development of cataracts.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. Association Between Cigarette Smoking Prevalence and Income Level: A Systematic Review and Meta-Analysis.

    PubMed

    Casetta, Brunilda; Videla, Alejandro J; Bardach, Ariel; Morello, Paola; Soto, Natalie; Lee, Kelly; Camacho, Paul Anthony; Hermoza Moquillaza, Rocío Victoria; Ciapponi, Agustín

    2016-09-27

    Previous evidence linked low socioeconomic status with higher smoking prevalence. Our objective was to assess the strength of this association in the world population, updating a previous work. Systematic review and meta-analysis of observational studies. Subgroup analyses included continents, WHO regions, country mortality levels, gender, age, risk of bias, and study publication date. Independent reviewers selected studies, assessed potential bias and extracted data. We searched MEDLINE, EMBASE, CENTRAL, SOCINDEX, AFRICAN INDEX MEDICUS, and LILACS, and other sources from 1989 to 2013 reporting direct measurements of income and current cigarette smoking. We retrieved 13,583 articles and included 93 for meta-analysis. Median smoking prevalence was 17.8% (range 3-70%). Lower income was consistently associated with higher smoking prevalence (odds ratio [OR]: 1.45; 95% confidence interval [CI]: 1.35-1.56). This association was statistically significant in the subgroup analysis by WHO regions for the Americas (OR: 1.54; 95% CI: 1.42-1.68), South East Asia (OR: 1.53; 95% CI: 1.10-2.00), Europe (OR: 1.45; 95% CI: 1.29-1.63), and Western Pacific (OR: 1.32; 95% CI: 1.02-1.72), and in studies conducted during 1990s (OR: 1.42; 95% CI: 1.24-1.62) and 2000s (OR: 1.48; 95%CI: 1.30-1.64). Likewise, it was noted in low-mortality countries (OR: 1.48; 95% CI: 1.37-1.60) and for both genders. Prevalence was highest in the lowest income levels compared to the middle (OR: 1.69; 95% CI: 1.49-1.92), followed by the middle level compared to the highest (OR: 1.31; 95% CI: 1.20-1.43). Our results show that current cigarette smoking was significantly associated with lower income worldwide and across subgroups, suggesting a dose-response relationship. This unique updated systematic review shows a consistent inverse dose-response relationship between cigarette smoking and income level, present among most geographical areas and country characteristics. Public health measures should take into

  4. Meta-analysis identifies common variants associated with body mass index in East Asians

    PubMed Central

    Wen, Wanqing; Cho, Yoon Shin; Zheng, Wei; Dorajoo, Rajkumar; Kato, Norihiro; Qi, Lu; Chen, Chien-Hsiun; Delahanty, Ryan J.; Okada, Yukinori; Tabara, Yasuharu; Gu, Dongfeng; Zhu, Dingliang; Haiman, Christopher A.; Mo, Zengnan; Gao, Yu-Tang; Saw, Seang Mei; Go, Min Jin; Takeuchi, Fumihiko; Chang, Li-Ching; Kokubo, Yoshihiro; Liang, Jun; Hao, Mei; Marchand, Loic Le; Zhang, Yi; Hu, Yanling; Wong, Tien Yin; Long, Jirong; Han, Bok-Ghee; Kubo, Michiaki; Yamamoto, Ken; Su, Mei-Hsin; Miki, Tetsuro; Henderson, Brian E.; Song, Huaidong; Tan, Aihua; He, Jiang; Ng, Daniel P.-K.; Cai, Qiuyin; Tsunoda, Tatsuhiko; Tsai, Fuu-Jen; Iwai, Naoharu; Chen, Gary K.; Shi, Jiajun; Xu, Jianfeng; Sim, Xueling; Xiang, Yong-Bing; Maeda, Shiro; Ong, Rick T.H.; Li, Chun; Nakamura, Yusuke; Aung, Tin; Kamatani, Naoyuki; Liu, Jian Jun; Lu, Wei; Yokota, Mitsuhiro; Seielstad, Mark; Fann, Cathy S.J.; Wu, Jer-Yuarn; Lee, Jong-Young; Hu, Frank B.; Tanaka, Toshihiro; Tai, E. Shyong; Shu, Xiao Ou

    2012-01-01

    Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We conducted a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 East Asians, followed by in silico and de novo replication in 37,691 and 17,642 additional East Asians, respectively. We identified ten BMI-associated loci at the genome-wide significance level (P<5.0×10−8), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR/QPCTL, ADCY3/RBJ, BDNF, and MAP2K5) and three novel loci in or near the CDKAL1,PCSK1, and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a new locus near PAX6, which all had P<5.0×10−7. Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations. PMID:22344219

  5. 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

  6. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins.

    PubMed

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

    2016-12-01

    In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1×10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5×10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment. Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. Association between Toxoplasma gondii types and outcomes of human infection: A meta-analysis.

    PubMed

    Xia, Jing; Cheng, Xin-Yu; Wang, Xiao-Jun; Peng, Hong-Juan

    2017-09-01

    The virulence and pathogenicity of various types of Toxoplasma gondii differ considerably in mice. Recent studies have claimed that similar phenomenon was observed in humans, but no relevant studies have been performed to validate this finding. In addition, reports showing association between a given T. gondii type and outcomes of human infection yielded conflicting results. To provide a more precise estimation of the association and a more reliable conclusion on this subject, we performed this meta-analysis. Relevant literatures were identified in multiple databases and selected based on strict screening. T. gondii-type proportions among different severities of infection were calculated and compared using Fisher's exact test. Pooled odds ratios (OR) were calculated. Our results showed that the difference among T. gondii-type proportions was significant (p < 0.0001). In addition, significant associations were detected between Type I strains infection and congenital toxoplasmosis (OR: 1.91, p = 0.0009), Type III strains infection and pulmonary toxoplasmosis (OR: 5.15, p = 0.04). In our subgroup analysis, Type I strains were significantly associated with cerebral toxoplasmosis in offspring (OR: 1.81, p = 0.02). This result indicated that different types of T. gondii exhibited different virulence and caused different outcomes in humans.

  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 RAGE polymorphisms and cancer risk: a meta-analysis of 27 studies.

    PubMed

    Xia, Wenjie; Xu, Youtao; Mao, Qixing; Dong, Gaochao; Shi, Run; Wang, Jie; Zheng, YanYan; Xu, Lin; Jiang, Feng

    2015-02-01

    The receptor for advanced glycation end products (RAGE), a member of immunoglobulin superfamily, has been proved to stimulate survival, growth, and metastatic spread of cancers cells. Evidence suggested that the 82G/S, -374T/A, and -429T/C polymorphisms in RAGE promoter region might affect the risk of cancer; however, data from epidemiological studies showed conflicting results that remain to be further clarified. This meta-analysis was performed to derive a more precise estimation of 82G/S, -374T/A, and -429T/C polymorphisms and risk of cancer. A comprehensive electronic search was conducted for articles published up until December 2, 2014, in Medline (PubMed), Embase, the Cochrane Library and Google Scholar. A total of 12 case-control articles were included in this meta-analysis, providing 3,374 cases and 3,757 controls for 82G/S, 2,936 cases and 3,338 controls for -374T/A, and 2,882 cases and 3,279 controls for -429T/C specifically. The pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to evaluate the associations with risk of cancer. Overall, we observed significantly increased risk of cancer in relation to 82G/S (A vs. G: OR 1.321, 95 % CI 1.164-1.499, P het 0.028; AA vs. GG: OR 1.823, 95 % CI 1.541-2.157, P het < 0.001; AG vs. GG: OR 1.399, 95 % CI 1.120-1.746, P het 0.002; GA+AA vs. GG: OR 1.470, 95 % CI 1.187-1.821, P het 0.002; AA vs. GG+AG: OR 1.416, 95 % CI 1.158-1.732, P het 0.107) and reduced risk of cancer in relation to -374T/A (AA vs. TT: OR 0.818, 95 % CI 0.686-0.976, P het 0.025; A vs. T: OR 0.908, 95 % CI 0.840-0.981, P het 0.014). In subgroup analysis for 82G/S, a significantly elevated cancer risk was indicated in the population of Asian and patients with lung cancer, and for -374T/A, reduced risk was indicated in population of Caucasian and patients with lung cancer and breast cancer. But no significant association was observed between -429T/C and risk of cancer. Thus, this meta-analysis revealed that 82G

  10. Association between toll-like receptors 9 (TLR9) gene polymorphism and risk of pulmonary tuberculosis: meta-analysis.

    PubMed

    Chen, Zhi; Wang, Wei; Liang, Jianqin; Wang, Jinhe; Feng, Shisheng; Zhang, Guangyu

    2015-05-08

    Previous studies indicated that the single nucleotide polymorphisms (SNPs) in TLR9 gene might be associated with Tuberculosis (TB) risk. However, the results are inconsistent and inconclusive. 1745 articles from four databases were involved in our study. A meta-analysis on the associations between the seven polymorphisms and TB risk was carried out by comparison using different genetic models. In this systematic review 8 studies from seven English articles were analyzed. Our results showed that rs352139 is significantly associated with TB risk (AA vs. AG, OR 0.77, 95% CI 0.65-0.92, P = 0.004). In the ethnic subgroup analysis, Indonesians with AA genotype had a decreased susceptibility while Mexicans with GG allele had an increased risk. The meta-analysis indicated that rs352139 polymorphism might be associated with decreased TB risk in Indonesians whereas increased risk in Mexicans. Whether the observed association was due to causal effect needs to be further studied.

  11. Bidirectional association between depression and sexual dysfunction: a systematic review and meta-analysis.

    PubMed

    Atlantis, Evan; Sullivan, Thomas

    2012-06-01

    Depression is frequently associated with sexual dysfunction in both men and women. To examine whether depression predicts sexual dysfunction and, conversely, whether sexual dysfunction predicts depression. A systematic review and meta-analysis was conducted. PubMed and EMBASE biomedical answers electronic databases were searched for relevant studies up to November 2011. Reference lists of relevant articles were hand-searched and expert opinions were sought. Studies identified for inclusion had to be prospective cohort studies in adult populations that reported an association between depression and sexual dysfunction variables. Odds ratios (ORs), prioritized where available, or relative risks (RRs) were pooled across studies using random-effects meta-analysis models. Eight citations included for review yielded six studies on depression and risk of sexual dysfunction in 3,285 participants followed for 2-9 years, and six studies on sexual dysfunction and risk of depression in 11,171 participants followed for 1-10 years. Depression increased the risk of sexual dysfunction in pooled unadjusted (RR/OR 1.52 with 95% confidence intervals [1.02, 2.26]) and adjusted (RR/OR 1.71 [1.05, 2.78]) meta-analyses but not in the partially adjusted model (RR/OR 1.41 [0.90, 2.23]). There was significant heterogeneity between studies, but after removal of a single outlying study was diminished and the pooled partially adjusted, RR/OR increased to 1.69 (1.15, 2.47). Sexual dysfunction increased the odds of depression in the pooled unadjusted (OR 2.30 [1.74, 3.03]), adjusted (OR 3.12 [1.66, 5.85]), and partially adjusted (OR 2.71 [1.93, 3.79]) meta-analyses; heterogeneity was significant only in the adjusted model. Meta-regression analyses did not detect significant sources of heterogeneity in either examination. Clinicians should be aware of a bidirectional association between depression and sexual dysfunction. Patients reporting sexual dysfunction should be routinely screened for

  12. 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

  13. Replication and Meta-Analysis of Candidate Loci Identified Variation at RAB3GAP1 Associated With Keratoconus

    PubMed Central

    Bae, Ha Ae; Mills, Richard A. D.; Lindsay, Richard G.; Phillips, Tony; Coster, Douglas J.; Mitchell, Paul; Wang, Jie Jin; Craig, Jamie E.; Burdon, Kathryn P.

    2013-01-01

    Purpose. Keratoconus is a common complex corneal ectasia that can lead to severe visual impairment. Although a genetic component is well recognized, the genetic risk factors for keratoconus are yet to be fully elucidated. A recent genome-wide association study (GWAS) by Li et al. identified 15 potentially associated single nucleotide polymorphisms (SNPs). Here, we aimed to replicate these associations, and conduct a meta-analysis of the current and previous studies. Methods. We genotyped the 15 reported associated SNPs in 524 Australian Caucasian cases with keratoconus and 2761 controls. Association analysis was conducted in PLINK. A meta-analysis of this study with the adjusted P values of the previously published GWAS was conducted using the method of Fisher to combine P values. Results. Our Australian cohort showed association (P < 0.003) at SNPs near RAB3GAP1, KCND3, IMMPL2, and in a gene desert on chromosome 13q33.3, providing evidence of replication of the published results. The meta-analysis showed SNP rs4954218 near RAB3GAP1 gene was associated significantly with keratoconus, with P = 9.26 × 10−9 passing the genome-wide significance level. Conclusions. Although the mechanism of disease association is yet to be determined, SNP rs4954218 is associated consistently with keratoconus and likely tags a functional variant that contributes to disease susceptibility. PMID:23833071

  14. Modifiable partner factors associated with perinatal depression and anxiety: a systematic review and meta-analysis.

    PubMed

    Pilkington, Pamela D; Milne, Lisa C; Cairns, Kathryn E; Lewis, James; Whelan, Thomas A

    2015-06-01

    Perinatal distress is a significant public health problem that adversely impacts the individual and their family. The primary objective of this systematic review and meta-analysis was to identify factors that partners can modify to protect each other from developing perinatal depression and anxiety. In accordance with the PRISMA statement, we reviewed the risk and protective factors associated with perinatal depression and anxiety symptoms that partners can potentially modify without professional assistance (PROSPERO reference CRD42014007524). Participants were new or expectant parents aged 16 years or older. The partner factors were sub-grouped into themes (e.g., instrumental support) based on a content analysis of the scale items and measure descriptions. A series of meta-analyses were conducted to estimate the pooled effect sizes of associations. We included 120 publications, reporting 245 associations with depression and 44 with anxiety. Partner factors with sound evidence that they protect against both perinatal depression and anxiety are: emotional closeness and global support. Partner factors with a sound evidence base for depression only are communication, conflict, emotional and instrumental support, and relationship satisfaction. This review is limited by the lack of generalizability to single parents and the inability to systematically review moderators and mediators, or control for baseline symptoms. The findings suggest that future prevention programs targeting perinatal depression and anxiety should aim to enhance relationship satisfaction, communication, and emotional closeness, facilitate instrumental and emotional support, and minimize conflict between partners. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. 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

  16. 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.

  17. Association Between Chronic Respiratory Diseases and Helicobacter pylori: A Meta-Analysis.

    PubMed

    Wang, Lijie; Guan, Yan; Li, Yan; Liu, Xiuju; Zhang, Yakun; Wang, Fuxia; Kong, Lingling; Guo, Qisen

    2015-06-01

    The prevalence of chronic respiratory diseases (CRDs), including chronic bronchitis and chronic obstructive pulmonary disease (COPD), has increased significantly over the past decades. Several studies suggest that Helicobacter pylori infection may be related to the development of CRDs, but the results were not consistent. We carried out a meta-analysis to evaluate the potential association of H.pylori infection with CRDs. We conducted a systematic literature search in PubMed, Embase, Ovid, Google Scholar and CNKI from inception to October 31, 2013. The following search terms were used: "chronic respiratory disease," "chronic bronchitis," "chronic obstructive pulmonary disease" or "COPD" in combination with "Helicobacter pylori" or "Campylobacter pylori." According to established inclusion criteria, we selected all eligible published papers and then extracted essential data. To evaluate the association of H.pylori with chronic bronchitis and COPD, an overall analysis and subgroup analyses were conducted. A total of 9 case-control studies comprising 782 cases and 815 controls were included in the study. Pooled ORs were 2.30 (95%CI: 1.85-2.85) in the overall analysis, 2.90 (95%CI: 2.04-4.13) in the chronic bronchitis subgroup, and 2.11 (95%CI: 1.35-3.29) in the COPD subgroup. The results of the overall analysis and subgroup analyzed suggest a significant association between H.pylori and CRDs. Further studies are needed to clarify the pathogenetic mechanisms involved. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  18. 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.

  19. A systematic review and meta-analysis of the association between unintended pregnancy and perinatal depression.

    PubMed

    Abajobir, Amanuel Alemu; Maravilla, Joemer Calderon; Alati, Rosa; Najman, Jackob Moses

    2016-03-01

    There is a growing interest in exploring maternal mental health effects of unintended pregnancies carried to term. However, the evidence base from a small number of available studies is characterised by considerable variability, inconsistency and inconclusive findings. We present a systematic review and meta-analysis of all available studies on unintended pregnancy as these are related to maternal depression. Using PRISMA guideline, we systematically reviewed and meta-analysed studies reporting an association between unintended pregnancy and maternal depression from PubMed, EMBASE, PsychINFO and Google Scholar. We used a priori set criteria and included details of quality and magnitude of effect sizes. Sample sizes, adjusted odds ratios and standard errors were extracted. Random effects were used to calculate pooled estimates in Stata 13. Cochran's Q, I(2) and meta-bias statistics assessed heterogeneity and publication bias of included studies. Meta-bias and funnel plot of inverse variance detected no publication bias. Overall prevalence of maternal depression in unintended pregnancy was 21%. Unintended pregnancy was significantly associated with maternal depression. Despite statistically significant heterogeneities of included studies, sub-group analyses revealed positive and significant associations by types of unintended pregnancies, timing of measurements with respect to pregnancy and childbirth, study designs and settings. The prevalence of perinatal depression is two-fold in women with unintended pregnancy. Perinatal care settings may screen pregnancy intention and depression of women backed by integrating family planning and mental health services. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. 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

  1. 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

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

    PubMed Central

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

    2013-01-01

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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Association between Psoriasis and Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis.

    PubMed

    Li, Xin; Kong, Lingjun; Li, Fulun; Chen, Chen; Xu, Rong; Wang, Hongshen; Peng, Shiguang; Zhou, Min; Li, Bin

    2015-01-01

    Psoriasis is considered a systemic inflammatory disorder. Previous studies have reported conflicting positive or negative correlations between psoriasis and chronic obstructive pulmonary disease. We performed a meta-analysis to determine whether there is an associated risk between psoriasis and chronic obstructive pulmonary disease. We performed a complete 30-year literature search of MEDLINE, Embase, and Cochrane Central Register databases on this topic. Four observational studies with a total of 13,418 subjects were identified. The odds ratios of chronic obstructive pulmonary disease in subjects with psoriasis/mild-to-moderate psoriasis were analyzed using the random-effects model, while the odds ratios of chronic obstructive pulmonary disease in subjects with severe psoriasis and current smoking in subjects with psoriasis were analyzed using the fixed-effect model. We found that psoriasis patients were at a greater risk of developing chronic obstructive pulmonary disease than the general population (odds ratio, 1.90; 95% confidence interval, 1.36-2.65) and that the association between of psoriasis and with chronic obstructive pulmonary disease was stronger among patients with severe psoriasis (odds ratio, 2.15; 95% confidence interval, 1.26-3.67). Psoriasis patients should be advised to cease smoking to reduce their risk of COPD. Moreover, identification of this potential risk may enable earlier implementation of preventive measures for reduction comorbidity and mortality rates.

  8. Meta-analysis identifies four new loci associated with testicular germ cell tumor

    PubMed Central

    Chung, Charles C.; Kanetsky, Peter A.; Wang, Zhaoming; Hildebrandt, Michelle A. T.; Koster, Roelof; Skotheim, Rolf I.; Kratz, Christian P.; Turnbull, Clare; Cortessis, Victoria K.; Bakken, Anne C.; Bishop, D. Timothy; Cook, Michael B.; Erickson, R. Loren; Fosså, Sophie D.; Jacobs, Kevin B.; Korde, Larissa A.; Kraggerud, Sigrid M.; Lothe, Ragnhild A.; Loud, Jennifer T.; Rahman, Nazneen; Skinner, Eila C.; Thomas, Duncan C.; Wu, Xifeng; Yeager, Meredith; Schumacher, Fredrick R.; Greene, Mark H.; Schwartz, Stephen M.; McGlynn, Katherine A.; Chanock, Stephen J.; Nathanson, Katherine L.

    2013-01-01

    We conducted a meta-analysis to identify new loci for testicular germ cell tumor (TGCT) susceptibility. In the discovery phase, 931 affected individuals and 1,975 controls from three genome wide association studies (GWAS) were analyzed. Replication was conducted in six independent sample sets totaling 3,211 affected individuals and 7,591 controls. In the combined analysis, TGCT risk was significantly associated with markers at four novel loci: 4q22.2 in HPGDS (per allele odds ratio (OR) 1.19, 95%CI 1.12–1.26, P = 1.11×10−8); 7p22.3 in MAD1L1 (OR 1.21, 95%CI 1.14–1.29, P = 5.59×10−9); 16q22.3 in RFWD3 (OR 1.26, 95%CI 1.18–1.34, P = 5.15×10−12); and 17q22 (rs9905704; OR 1.27, 95%CI 1.18–1.33; P = 4.32×10−13, and rs7221274; OR 1.20, 95%CI 1.12–1.28 P = 4.04×10−9), a locus which includes TEX14, RAD51C and PPM1E. The new TGCT susceptibility loci contain biologically plausible genes encoding proteins important for male germ cell development, chromosomal segregation and DNA damage response. PMID:23666239

  9. Differences in the association between empirically derived dietary patterns and cancer: a meta-analysis.

    PubMed

    Bella, Francesca; Godos, Justyna; Ippolito, Antonella; Di Prima, Alessia; Sciacca, Salvatore

    2017-06-01

    Plant-based dietary patterns have been associated with decreased cancer risk. The aim of the present study was to perform a meta-analysis of studies comparing empirically derived dietary patterns in relation to cancer risk. A systematic search of PubMed and EMBASE electronic databases was conducted. Eligible studies had an observational design and evaluated the association with cancer risk between a posteriori derived dietary patterns. Random-effects models were applied to calculate relative risks (RRs) of cancer between diets. Statistical heterogeneity and publication bias were explored. An increased risk of cancer for the adoption of high-meat compared to plant-based dietary patterns was found (RR =1.64, 95% CI: 1.02, 2.63). Lower risk of cancer for individuals adopting a plant-based dietary pattern over a mixed one was found (RR =0.88, 95% CI: 0.82, 0.95). In conclusion, plant-based dietary patterns can be considered a healthy choice over meat-based dietary patterns.

  10. 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.

  11. 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

  12. Association of Psoriasis and Metabolic Syndrome in Latin America: A Systematic Review and Meta-Analysis.

    PubMed

    Rodríguez-Zúñiga, M J M; Cortez-Franco, F; Quijano-Gomero, E

    2017-05-01

    Meta-analyses have found evidence of a relationship between psoriasis and metabolic syndrome, but Latin American populations have not been included. We performed a systematic review and meta-analysis of observational studies including adults with psoriasis and metabolic syndrome indexed in Medline, Scopus, SciELO, Google Scholar, Science Direct, and LILACS between 1980 and 2016. We computed pooled odds ratios (OR) with a random effects model and analyzed subgroups according to patient variables used in the studies. Five studies with a total of 241 patients with psoriasis were found; 46.5% of the patients also had metabolic syndrome (pooled OR, 2.63; 95% CI: 1.11-6.23; P=.03). In studies using the Adult Treatment Panel III (ATP-III) criteria for metabolic syndrome, the pooled OR was similar at 3.97 (95% CI: 1.27-21.42). Studies that included patients with chronic and severe disease detected higher risk for metabolic syndrome (pooled OR, 6.65; 95% CI: 3.32-13.31). Limitations are that few studies have been done in Latin America, heterogeneity was high, and inconsistency was found across studies. The association between psoriasis and metabolic syndrome is high in Latin America. The association is stronger when psoriasis is chronic and severe and when the ATP-III criteria are used for diagnosis. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. 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.

  14. Meta-analysis of the association between secondhand smoke exposure and physician-diagnosed childhood asthma.

    PubMed

    Tinuoye, Olaitan; Pell, Jill P; Mackay, Daniel F

    2013-09-01

    Studies suggest an association between secondhand smoke exposure and the development of childhood asthma. Several countries are considering legislation to protect children from exposure. A systematic review was conducted using MEDLINE, Embase, PubMed, and Web of Knowledge databases and a random effects meta-analysis was undertaken. Heterogeneity was assessed using the I (2) test. Publication and small study biases were examined visually using a funnel plot and tested formally using Egger test. Univariate and multivariate meta-regression analyses were undertaken, including a subgroup analysis of cohort studies to examine the effect of duration of follow-up. Twenty relevant studies were identified (14 cross-sectional, 4 cohort, and 2 case-control) and provided 31 estimates of effect size. The pooled odds ratio was 1.32 (95% CI: 1.23, 1.42, p < .001). There was moderate heterogeneity (I (2) = 74.2%, p < .001). On multivariate meta-regression analysis, effect size estimates were significantly higher for case-control studies (p = .042) and those using self-reported exposure to secondhand smoke (p = .050). There was no evidence of significant publication or small study bias (Egger test, p = .121). There is now consistent evidence of a modest association between secondhand smoke and physician-diagnosed childhood asthma. These results lend support to continued efforts to reduce childhood exposure to secondhand smoke.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

    PubMed Central

    López-Isac, Elena; Martín, Jose-Ezequiel; Assassi, Shervin; Simeón, Carmen P; Carreira, Patricia; Ortego-Centeno, Norberto; Freire, Mayka; Beltrán, Emma; Narváez, Javier; Alegre-Sancho, Juan J; Fernández-Gutiérrez, Benjamín; Balsa, Alejandro; Ortiz, Ana M; González-Gay, Miguel A; Beretta, Lorenzo; Santaniello, Alessandro; Bellocchi, Chiara; Lunardi, Claudio; Moroncini, Gianluca; Gabrielli, Armando; Witte, Torsten; Hunzelmann, Nicolas; Distler, Jörg HW; Riekemasten, Gabriella; van der Helm-van Mil, Annete H; de Vries-Bouwstra, Jeska; Magro-Checa, Cesar; Voskuyl, Alexandre E; Vonk, Madelon C; Molberg, Øyvind; Merriman, Tony; Hesselstrand, Roger; Nordin, Annika; Padyukov, Leonid; Herrick, Ariane; Eyre, Steve; Koeleman, Bobby PC; Denton, Christopher P; Fonseca, Carmen; Radstake, Timothy RDJ; Worthington, Jane; Mayes, Maureen D; Martín, Javier

    2017-01-01

    Objectives Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc-RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposing-direction allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 × 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 × 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci. PMID:27111665

  20. 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

  1. Association of rs1122608 with Coronary Artery Disease and Lipid Profile: A Meta-analysis.

    PubMed

    Liu, Shuo; Xiu, Bingqiu; Liu, Jingdong; Xue, Aimin; Tang, Qiqun; Shen, Yiwen; Xie, Jianhui

    2016-05-01

    It has been reported that rs1122608 adjacent to low-density lipoprotein cholesterol receptor (LDLR) locus is associated with the risk of coronary artery disease (CAD) and blood lipid profile in the Caucasian population. Due to the contradictory results in the Asian population, we conducted a meta-analysis to systematically summarize and clarify the association between rs1122608 with CAD risk and lipid profile. A systematic search regarding studies on the association of rs1122608 with CAD risk and lipid profile was conducted in databases including PubMed, Embase, and Cochrane library. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. A total of five case-control studies were included in this study. A statistically significant association was identified between rs1122608-G allele and CAD risk in overall analysis (OR = 2.09, 95% CI 1.48-2.97) and in both Asian (OR = 1.82, 95% CI 1.04-3.18) and Caucasian subgroups (OR = 2.31, 95% CI 1.48-3.60). The rs1122608-G allele was associated with increased triglyceride (TG) level (OR = 1.25, 95% CI 1.03-1.52), but not with total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), or LDL cholesterol level. Moreover, the rs1122608-G allele is associated with increased CAD risk in the Asian male population (OR = 3.37, 95% CI 1.51-9.86) but not in the Asian female population. The rs1122608 is associated with the risk of CAD and TG level. The rs1122608-G allele was a significant risk factor of CAD in the Asian male population but not in the Asian female population. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  2. [Association of atopic eczema and attention-deficit/hyperactivity disorder - meta-analysis of epidemiologic studies].

    PubMed

    Schmitt, Jochen; Apfelbacher, Christian; Heinrich, Joachim; Weidinger, Stephan; Romanos, Marcel

    2013-01-01

    Atopic dermatitis (AD) and attention-deficit/hyperactivity disorder (ADHD) are frequent paediatric conditions with high medical relevance. A possible relationship between atopic diseases (i.e., AD, asthma, and allergic rhinitis) has long been discussed, but convincing evidence is still missing. We investigated the relationship between AD and ADHD in two cross-sectional studies and in two birth cohort studies considering lifestyle factors, environmental factors, and atopic comorbidities as potential confounders. To quantify the strength of association between AD and ADHD, data from the four epidemiologic studies were summarized by means of a meta-analysis. Odds ratios (OR) were pooled for the association between prevalent or previous AD and prevalent ADHD from the four studies adjusted for age, sex, and atopic comorbidity (allergic rhinitis, asthma). The epidemiologic studies conducted consistently indicate an association between AD and ADHD which is independent of environmental exposures and other comorbidities. Particularly infant AD appears to be associated with later development of ADHD symptoms. Sleeping problems due to AD are suggested as playing an important role for the observed association between AD and ADHD. The pooled OR (95 % confidence interval (95 %CI)) for the association between AD and ADHD was 1.43 (1.25-1.64). Four new epidemiologic studies consistently indicate a positive association between AD and ADHD. Compared to children without AD, children with previous or prevalent AD have an approximately 43 % increased risk to be diagnosed with ADHD or to display clinical ADHD symptoms. Following our findings, the biological mechanisms underlying the observed comorbidity between AD and ADHD require further investigation in order to subsequently develop targeted therapeutic and preventive strategies.

  3. 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.

  4. Exercise-associated DNA methylation change in skeletal muscle and the importance of imprinted genes: a bioinformatics meta-analysis.

    PubMed

    Brown, William M

    2015-12-01

    Epigenetics is the study of processes--beyond DNA sequence alteration--producing heritable characteristics. For example, DNA methylation modifies gene expression without altering the nucleotide sequence. A well-studied DNA methylation-based phenomenon is genomic imprinting (ie, genotype-independent parent-of-origin effects). We aimed to elucidate: (1) the effect of exercise on DNA methylation and (2) the role of imprinted genes in skeletal muscle gene networks (ie, gene group functional profiling analyses). Gene ontology (ie, gene product elucidation)/meta-analysis. 26 skeletal muscle and 86 imprinted genes were subjected to g:Profiler ontology analysis. Meta-analysis assessed exercise-associated DNA methylation change. g:Profiler found four muscle gene networks with imprinted loci. Meta-analysis identified 16 articles (387 genes/1580 individuals) associated with exercise. Age, method, sample size, sex and tissue variation could elevate effect size bias. Only skeletal muscle gene networks including imprinted genes were reported. Exercise-associated effect sizes were calculated by gene. Age, method, sample size, sex and tissue variation were moderators. Six imprinted loci (RB1, MEG3, UBE3A, PLAGL1, SGCE, INS) were important for muscle gene networks, while meta-analysis uncovered five exercise-associated imprinted loci (KCNQ1, MEG3, GRB10, L3MBTL1, PLAGL1). DNA methylation decreased with exercise (60% of loci). Exercise-associated DNA methylation change was stronger among older people (ie, age accounted for 30% of the variation). Among older people, genes exhibiting DNA methylation decreases were part of a microRNA-regulated gene network functioning to suppress cancer. Imprinted genes were identified in skeletal muscle gene networks and exercise-associated DNA methylation change. Exercise-associated DNA methylation modification could rewind the 'epigenetic clock' as we age. CRD42014009800. Published by the BMJ Publishing Group Limited. For permission to use (where

  5. 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.

  6. Meta-Analysis of the Association between Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Recurrent Pregnancy Loss

    PubMed Central

    Li, Xuejiao; Liu, Yukun; Zhang, Rui; Tan, Jianping; Chen, Libin; Liu, Yinglin

    2015-01-01

    Background The association between plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and recurrent pregnancy loss (RPL) risk is still contradictory. We thus performed a meta-analysis. Material/Methods Relevant studies were searched for in PubMed, Web of Science, Embase, and Cochrane Library. An odds ratio (OR) with a 95% confidence interval (CI) was used to assess the association between PAI-1 4G/5G polymorphism and RPL risk. Results A total of 22 studies with 4306 cases and 3076 controls were included in this meta-analysis. We found that PAI-1 4G/5G polymorphism was significantly associated with an increased RPL risk (OR=1.89; 95% CI 1.34–2.67; P=0.0003). In the subgroup analysis by race, PAI-1 4G/5G polymorphism was significantly associated with an increased RPL risk in Caucasians (OR=2.23; 95% CI 1.44–3.46; P=0.0003). However, no significant association was observed in Asians (OR=1.47; 95% CI 0.84–2.59; P=0.18). Conclusions In conclusion, this meta-analysis suggests that PAI-1 4G/5G polymorphism might be associated with RPL development in Caucasians. PMID:25862335

  7. Meta-analysis of the association between plasminogen activator inhibitor-1 4G/5G polymorphism and recurrent pregnancy loss.

    PubMed

    Li, Xuejiao; Liu, Yukun; Zhang, Rui; Tan, Jianping; Chen, Libin; Liu, Yinglin

    2015-04-11

    The association between plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and recurrent pregnancy loss (RPL) risk is still contradictory. We thus performed a meta-analysis. Relevant studies were searched for in PubMed, Web of Science, Embase, and Cochrane Library. An odds ratio (OR) with a 95% confidence interval (CI) was used to assess the association between PAI-1 4G/5G polymorphism and RPL risk. A total of 22 studies with 4306 cases and 3076 controls were included in this meta-analysis. We found that PAI-1 4G/5G polymorphism was significantly associated with an increased RPL risk (OR=1.89; 95% CI 1.34-2.67; P=0.0003). In the subgroup analysis by race, PAI-1 4G/5G polymorphism was significantly associated with an increased RPL risk in Caucasians (OR=2.23; 95% CI 1.44-3.46; P=0.0003). However, no significant association was observed in Asians (OR=1.47; 95% CI 0.84-2.59; P=0.18). In conclusion, this meta-analysis suggests that PAI-1 4G/5G polymorphism might be associated with RPL development in Caucasians.

  8. No association between ApoE and schizophrenia: Evidence of systematic review and updated meta-analysis.

    PubMed

    González-Castro, Thelma Beatriz; Tovilla-Zárate, Carlos Alfonso; Hernández-Díaz, Yazmín; Fresán, Ana; Juárez-Rojop, Isela E; Ble-Castillo, Jorge L; López-Narváez, Lilia; Genis, Alma; Hernández-Alvarado, Mervyn Manuel

    2015-12-01

    Schizophrenia affects between 0.3% and 2% of the worldwide population. A genetic contribution has been postulated in the development of this disorder. Genes such as ApoE have been implicated in the neurodevelopment associated with schizophrenia in case-control and meta-analysis studies, but the results remain inconclusive. Due to this, the aim of the present study was to explore the association between ApoE and schizophrenia through a meta-analysis. We collected all relevant studies by searching PubMed and EBSCO databases. The pooled odds ratios with 95% confidence intervals were calculated to estimate the association. The following models were evaluated: A) ε4 vs ε3, B) ε4 vs ε2, C) ε4 vs ε3+ε2, D) Caucasian population and E) Asian population. Statistical analyses were performed using EPIDAT 3.1 software. The meta-analyses comprised 28 association studies, which included 4703 controls and 3452 subjects with schizophrenia. A significant protective effect was found for allele ε3 in the Asian population (OR=0.73, 95% CI=0.54-0.98). No significant associations were observed in the other models and populations analyzed. Our meta-analysis suggests a protective association between ApoE allele ε3 and schizophrenia in the Asian population. Copyright © 2015. Published by Elsevier B.V.

  9. 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

  10. Lack of association between endothelial nitric oxide synthase gene polymorphisms with vasculitis: a meta-analysis.

    PubMed

    Cheng, Y; Xiong, M; Liu, Y; Tang, B

    2015-01-01

    We carried out this meta-analysis to evaluate the relationship between eNOS polymorphisms (G894T, T-786C, and intron-4ba) and vasculitis. We systematically searched PubMed, EMBASE and the Cochrane Library for related genetic association studies. The associations between the G894T, T-786C and intron 4ba polymorphisms of eNOS and vasculitis were conducted using the recessive model and the dominant model. Odds ratio (OR) with 95% confidence interval (CI) of each study were calculated. Cochran's Q test was used to evaluate the between-study heterogeneity. A total of 17 studies were included in our study. Twelve studies with 1213 cases and 1499 controls were included in the G894T association study. The pooled OR of T allele compared to C allele in recessive model was 1.19 (95%CI: 0.76-1.87, p=0.44) in dominant model and was 1.25 (95%CI: 0.70-2.23, p=0.56) in recessive model, respectively. Nine studies with 910 cases and 1062 controls were included in the intron -4ba association study. The pooled OR of b allele compared with intron-4a allele was 1.02 (95%CI: 0.60-1.72, p=0.95) in dominant model and was 0.84 (95%CI: 0.58-1.21, p=0.35) in recessive model. No association was found between T-786C and vasculitis in both the dominant 0.81(95% CI: 0.59-1.11, p=0.19) and recessive model 0.87 (95%CI: 0.55-1.36, p=0.53). The eNOS G894T, T-786C and intron4ba polymorphisms are not associated with vasculitis.

  11. Meta-analysis of the association between dietary inflammatory index (DII) and cancer outcomes.

    PubMed

    Fowler, Mackenzie E; Akinyemiju, Tomi F

    2017-08-10

    Proinflammatory dietary patterns have been associated with increased cancer risk and mortality. We present a systematic review and meta-analysis of the current published literature on a dietary inflammatory index (DII) score and its association with cancer risk and mortality outcomes. Published articles from online databases (PubMed, Scopus, and Embase) examining the association between DII and any cancer risk, incidence, or mortality between 1980 and November 2016 were selected for review. Results of studies meeting inclusion criteria were summarized and meta-analyzed using STATA to generate summary measures of association across studies. Sixty-three published articles were identified from the search, and following title, abstract and full-text review, twenty-four studies met inclusion criteria. All articles calculated DII scores based on study-specific food-frequency questionnaires using methodology from the same article. Of the 24 included studies, 13 were case-control, 6 were prospective cohort, 1 was a retrospective cohort, 3 were RCTs, and 1 did not specify study design. The most common cancers examined were colorectal, breast, lung, and prostate. Individuals in the highest versus lowest DII categories had 25% increased risk of overall cancer incidence (RR: 1.25, 95% CI: 1.16-1.35), 75% higher odds of cancer (OR: 1.75, 95% CI: 1.43-2.16) and 67% increased risk of cancer mortality (RR: 1.67, 95% CI: 1.13-2.48). Upon stratification for cancer type, positive associations remained (RRbreast : RR: 1.12, 95% CI: 1.03-1.22) (RRcolorectal : 1.33, 95% CI: 1.22-1.46) (RRlung : 1.30, 95% CI: 1.13-1.50). There were consistent and significant positive associations between higher DII and cancer incidence and mortality across cancer types, study populations, and study design. © 2017 UICC.

  12. 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

  13. Association between atrial fibrillation and silent cerebral infarctions: a systematic review and meta-analysis.

    PubMed

    Kalantarian, Shadi; Ay, Hakan; Gollub, Randy L; Lee, Hang; Retzepi, Kallirroi; Mansour, Moussa; Ruskin, Jeremy N

    2014-11-04

    Atrial fibrillation (AF) is a common cause of stroke. Silent cerebral infarctions (SCIs) are known to occur in the presence and absence of AF, but the association between these disorders has not been well-defined. To estimate the association between AF and SCIs and the prevalence of SCIs in stroke-free patients with AF. Searches of MEDLINE, PsycINFO, Cochrane Library, CINAHL, and EMBASE from inception to 8 May 2014 without language restrictions and manual screening of article references. Observational studies involving adults with AF and no clinical history of stroke or prosthetic valves who reported SCIs. Study characteristics and study quality were assessed in duplicate. Eleven studies including 5317 patients with mean ages from 50.0 to 83.6 years reported on the association between AF and SCIs. Autopsy studies were heterogeneous and low-quality; therefore, they were excluded from the meta-analysis of the risk estimates. When computed tomography (CT) and magnetic resonance imaging (MRI) studies were combined, AF was associated with SCIs in patients with no history of symptomatic stroke (odds ratio, 2.62 [95% CI, 1.81 to 3.80]; I(2) = 32.12%; P for heterogeneity = 0.118). This association was independent of AF type (paroxysmal vs. persistent). The results were not altered significantly when the analysis was restricted to studies that met at least 70% of the maximum possible quality score (odds ratio, 3.06 [CI, 2.24 to 4.19]). Seventeen studies reported the prevalence of SCIs. The overall prevalence of SCI lesions on MRI and CT among patients with AF was 40% and 22%, respectively. Most studies were cross-sectional, and autopsy studies were heterogeneous and not sufficiently sensitive to detect small lesions. Atrial fibrillation is associated with more than a 2-fold increase in the odds for SCI. Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, Massachusetts General Hospital.

  14. 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

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

    PubMed

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

    2016-01-01

    Lower muscle strength in midlife predicts disability and mortality in later life. Blood-borne factors, including growth differentiation factor 11 (GDF11), have been linked to muscle regeneration in animal models. We aimed to identify gene transcripts associated with muscle strength in adults. Meta-analysis of whole blood gene expression (overall 17,534 unique genes measured by microarray) and hand-grip strength in four independent cohorts (n = 7,781, ages: 20-104 yr, weighted mean = 56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, men/women). Expression levels of 221 genes were associated with strength after adjustment for cofactors and for multiple statistical testing, including ALAS2 (rate-limiting enzyme in heme synthesis), PRF1 (perforin, a cytotoxic protein associated with inflammation), IGF1R, and IGF2BP2 (both insulin like growth factor related). We identified statistical enrichment for hemoglobin biosynthesis, innate immune activation, and the stress response. Ten genes were associated only in younger individuals, four in men only and one in women only. For example, PIK3R2 (a negative regulator of PI3K/AKT growth pathway) was negatively associated with muscle strength in younger (<60 yr) individuals but not older (≥ 60 yr). We also show that 115 genes (52%) have not previously been linked to muscle in NCBI PubMed abstracts. This first large-scale transcriptome study of muscle strength in human adults confirmed associations with known pathways and provides new evidence for over half of the genes identified. There may be age- and sex-specific gene expression signatures in blood for muscle strength. Copyright © 2016 the American Physiological Society.

  16. 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.

  17. 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.

  18. 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.

  19. Is crossed laterality associated with academic achievement and intelligence? A systematic review and meta-analysis

    PubMed Central

    West, Gillian; Vadillo, Miguel A.

    2017-01-01

    Over the last century, sporadic research has suggested that people whose hand, eye, foot, or ear dominances are not consistently right- or left-sided are at special risk of suffering academic difficulties. This phenomenon is known as crossed laterality. Although the bulk of this research dates from 1960’s and 1970’s, crossed laterality is becoming increasingly popular in the area of school education, driving the creation of several interventions aimed at restoring or consolidating lateral dominance. However, the available evidence is fragmentary. To determine the impact of crossed laterality on academic achievement and intelligence, we conducted a systematic review and meta-analysis of articles published since 1900. The inclusion criteria for the review required that studies used one or more lateral preference tasks for at least two specific parts of the body; they included a valid measure of crossed laterality; they measured the impact of crossed laterality on academic achievement or intelligence; and they included participants between 3 and 17 years old. The final sample included 26 articles that covered a total population of 3578 children aged 5 to 12. Taken collectively, the results of these studies do not support the claim that there is a reliable association between crossed laterality and either academic achievement or intelligence. Along with this, we detected important shortcomings in the literature, such as considerable heterogeneity among the variables used to measure laterality and among the tasks utilized to measure the outcomes. The educational implications of these results are discussed. PMID:28846704

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

    PubMed

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

    2016-01-01

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

  1. 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

  2. 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.

  3. Risk factors associated with human Rift Valley fever infection: systematic review and meta-analysis.

    PubMed

    Nicholas, Dennis E; Jacobsen, Kathryn H; Waters, Nigel M

    2014-12-01

    To identify risk factors for human Rift Valley fever virus (RVFV) infection. A systematic review identified 17 articles reporting on 16 studies examining risk factors for RVFV. Pooled odds ratios (pOR) were calculated for exposures examined in four or more studies. Being male [pOR = 1.4 (1.0, 1.8)], contact with aborted animal tissue [pOR = 3.4 (1.6, 7.3)], birthing an animal [pOR = 3.2 (2.4, 4.2)], skinning an animal [pOR = 2.5 (1.9, 3.2)], slaughtering an animal [pOR = 2.4 (1.4, 4.1)] and drinking raw milk [pOR = 1.8 (1.2, 2.6)] were significantly associated with RVF infection after meta-analysis. Other potential risk factors include sheltering animals in the home and milking an animal, which may both involve contact with animal body fluids. Based on the identified risk factors, use of personal protective equipment and disinfectants by animal handlers may help reduce RVFV transmission during outbreaks. Milk pasteurisation and other possible preventive methods require further investigation. © 2014 John Wiley & Sons Ltd.

  4. 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

  5. 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.

  6. Association of NOD1 (CARD4) insertion/deletion polymorphism with susceptibility to IBD: A meta-analysis

    PubMed Central

    Lu, Wei-Guo; Zou, Yan-Feng; Feng, Xiao-Liang; Yuan, Feng-Lai; Gu, Yuan-Long; Li, Xia; Li, Cheng-Wan; Jin, Cheng; Li, Jian-Ping

    2010-01-01

    AIM: To find evidences about whether NOD1/CARD4 insertion/deletion polymorphism is associated with inflammatory bowel disease by meta-analysis. METHODS: We surveyed the studies on the association of NOD1/CARD4 insertion/deletion polymorphism with inflammatory bowel disease in PubMed. Meta-analysis was performed for genotypes GG/T vs T/T, GG/GG vs T/T, GG/T + GG/GG vs T/T, GG/GG vs T/T + GG/T, and GG allele vs T allele in a fixed/random effect model. RESULTS: We identified 8 studies (6439 cases and 4798 controls) in Caucasian populations using PubMed search. We found no association between NOD1/CARD4 insertion/deletion polymorphism and inflammatory bowel disease, Crohn’s disease, and ulcerative colitis. Stratification of cases by age showed that NOD1/CARD4 insertion/deletion polymorphism was associated with inflammatory bowel disease in younger age group at onset (< 40 years) (GG vs T: OR = 0.68, 95% CI: 0.50-0.93, P = 0.02; GG/T + GG/GG vs T/T: OR = 0.71, 95% CI: 0.59-0.85, P = 0.0003). CONCLUSION: This meta-analysis demonstrates an association between NOD1/CARD4 insertion/deletion polymorphism and inflammatory bowel disease in the younger age group at onset (< 40 years) in Caucasian populations. PMID:20818820

  7. Efficacy of Acupuncture for Psychological Symptoms Associated with Opioid Addiction: A Systematic Review and Meta-Analysis

    PubMed Central

    Boyuan, Zhang; Yang, Chen; Ke, Cheng; Xueyong, Shen; Sheng, Liu

    2014-01-01

    This review systematically assessed the clinical evidence for and against acupuncture as a treatment for psychological symptoms associated with opioid addiction. The database was accessed from MEDLINE and China Knowledge Resource Integrated Database. We included all randomized clinical trials published in Chinese and English regardless of their controls. Meta-analysis was performed using the RevMan software, version 5.2. We conducted a literature search of 16 databases from their inception to January 2014. Four studies from Western countries did not report any clinical gains in the treatment of psychological symptoms associated with opioid addiction. 10 of 12 studies from China have reported positive findings regarding the use of acupuncture to treat the psychological symptoms associated with opioid addiction. The methodological quality of the included studies was poor. The meta-analysis indicated that there was a significant difference between the treatment group and the control group for anxiety and depression associated with opioid addiction, although groups did not differ on opioid craving. This review and meta-analysis could not confirm that acupuncture was an effective treatment for psychological symptoms associated with opioid addiction. However, considering the potential of acupuncture demonstrated in the included studies, further rigorous randomized controlled trials with long followup are warranted. PMID:25530779

  8. 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

  9. Nine genetic polymorphisms associated with power athlete status - A Meta-Analysis.

    PubMed

    Weyerstraß, Jan; Stewart, Kelly; Wesselius, Anke; Zeegers, Maurice

    2017-06-21

    In this study the association between genetic polymorphisms and power athlete status with possible interference by race and sex was investigated to identify genetic variants favourable for becoming a power athlete. This meta-analysis included both, case-control and Cohort studies. Databases of PubMed and Web of Science were searched for studies reporting on genetic polymorphisms associated with the status of being a power athlete. Thirty-five articles published between 2008 and 2016 were identified as eligible including a total number of 5834 power athletes and 14,018 controls. A series of meta-analyses were conducted for each of the identified genetic polymorphisms associated with power athlete status. Odds ratios (ORs) based on the allele and genotype frequency with corresponding 95% confidence intervals (95%CI) were calculated per genetic variant. Heterogeneity of the studies was addressed by Chi-square based Q-statistics at 5% significance level and a fixed or random effects model was used in absence or presence of heterogeneity respectively. Stratified analyses were conducted by race and sex to explore potential sources of heterogeneity. Significant associations were found for the genetic polymorphisms in the ACE (rs4363, rs1799752), ACTN3 (rs1815739), AGT (rs699), IL6-174 (rs1800795), MnSOD (rs1799725), NOS3 (rs1799983, rs2070744) and SOD2 (rs4880) genes. Nine genetic polymorphisms have been identified in the meta-analyses to have a significant association with the status of being a power athlete. Nevertheless, more research on the investigated genes needs to be done to draw comprehensive conclusions. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. Associations of genetic variants in/near BMI-associated genes with type 2 diabetes: A systematic meta-analysis

    PubMed Central

    Xi, Bo; Takeuchi, Fumihiko; Meirhaeghe, Aline; Kato, Norihiro; Chambers, John C; Morris, Andrew P; Cho, Yoon Shin; Zhang, Weihua; Mohlke, Karen L; Kooner, Jaspal S; Shu, Xiao Ou; Pan, Hongwei; Tai, E Shyong; Pan, Haiyan; Wu, Jer-Yuarn; Zhou, Donghao; Chandak, Giriraj R

    2017-01-01

    Summary Objective Genome-wide association studies have identified many obesity/body mass index (BMI)-associated loci in Europeans and East Asians. Since then, a large number of studies have investigated the role of BMI-associated loci in the development of type 2 diabetes (T2D). However, the results have been inconsistent. The objective of this study was to investigate the associations of 11 obesity/BMI with T2D risk and explore how BMI influences this risk. Methods We retrieved published literature from PubMed and Embase. The pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using fixed- or random- effect model. Results In the meta-analysis of 42 studies for 11 obesity/BMI-associated loci, we observed a statistically significant association of FTO rs9939609 polymorphism (66,425 T2D cases/239,689 normoglycemic subjects; p=1.00×10-41) and six other variants with T2D risk (17,915 T2D cases/27,531 normoglycemic individuals: n=40,629 to 130,001; all p<0.001 for SH2B1 rs7498665, FAIM2 rs7138803, TMEM18 rs7561317, GNPDA2 rs10938397, BDNF rs925946 and NEGR1 rs2568958). After adjustment for BMI, the association remained statistically significant for four of the seven variants (all p<0.05 for FTO rs9939609, SH2B1 rs7498665, FAIM2 rs7138803, GNPDA2 rs10938397). Subgroup analysis by ethnicity demonstrated similar results. Conclusions This meta-analysis indicates that several BMI-associated variants are significantly associated with T2D risk. Some variants increase the T2D risk independent of obesity, while others mediate this risk through obesity. PMID:24528214

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. BDNF Val66Met and Cognition: All, None, or Some? A Meta-Analysis of the Genetic Association

    PubMed Central

    Mandelman, Samuel D.; Grigorenko, Elena L.

    2011-01-01

    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 the current study we conducted a meta-analysis that included 23 publications containing 31 independent samples comprised of 7,095 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. PMID:21980924

  3. Association between PON1 L55M polymorphism and ischemic stroke: a systematic review and meta-analysis

    PubMed Central

    Shao, Peng; Qu, Da-Jun; Song, Rui-Ying; Chen, Ming-Lu; Wang, Li-Hua

    2015-01-01

    Objective: The present study aims to evaluate the relation between PON1 L55M polymorphism and ischemic stroke by a meta-analysis method. Methods: English and Chinese databases were retrieved to find qualified studies; a random or fixed effects model was used to merge the odds ratio (OR); Q test was used to assess the heterogeneity among studies, and Egger’s test and funnel plot were used for the assessment of publication bias. Results: 14 studies were included in the meta-analysis; in total populations, there was no association between PON1 gene L55M polymorphism and ischemic stroke in additive, dominant, and recessive model, respectively. Furthermore, we did not found associations between L55M and ischemic stroke in Asian or Caucasian population. Conclusion: Available evidences suggested that L55M polymorphism had no effect on the risk of ischemic stroke. However, this conclusion needs further validation by larger sample and well-designed studies. PMID:26064233

  4. 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.

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

    PubMed

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

    2015-05-25

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

  6. 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.

  7. 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.

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

    PubMed Central

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

    2016-01-01

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

  9. 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.

    2017-05-01

    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.

  10. Association between the FTOrs8050136 polymorphism and cancer risk: a meta-analysis.

    PubMed

    Zhao, Jian; Huang, Xiaoyi; Yang, Mingyuan; Li, Ming; Zheng, Jianming

    2016-01-01

    A meta-analysis on cancer risk relevant to FTOrs8050136 polymorphism. To investigate the comprehensive effect of FTOrs8050136 polymorphism on cancer risk based on a pooled result. Carcinogenesis is closely related to obesity. Both obesity and cancer share common pathogenic factors such as hereditary susceptibility and environmental predisposition. Recently, several studies had reported that the FTOrs8050136 polymorphism, a genetic variation highly associated with obesity, can be a potential cancer risk factor, while these results were inconsistent. With the help of PubMed, EMBASE, Chinese National Knowledge Infrastructure considerable research was done for potential studies without language restriction. Pooled odds ratio combined with 95 % confidence interval was employed to evaluate the potential correlations, and subgroup analyses were performed based on the cancer types and ethnic populations. There were eight articles comprising 21,810 cases and 85,070 controls met the eligibility criteria. Overall, there was no significant association between the FTOrs8050136 polymorphism and cancer risk (P = 0.163). Subgroup analysis illustrated that no association existed between the FTOrs8050136 polymorphism and cancer risk in Caucasians (P = 0.809), Asians (P = 0.412) and the mixed population (P = 0.093). With regard to cancer types, the result suggested that the FTOrs8050136 polymorphism had no connection with pancreatic cancer (P = 0.089), endometrial cancer (P = 0.353), prostate cancer (P = 0.578), colorectal cancer (P = 0.054) and melanoma (P = 0.357), while the inverse result was obtained in the subgroup of papillary thyroid cancer (P = 0.010). The FTOrs8050136 polymorphism may be not associated with carcinogenesis apart from papillary thyroid cancer, and further studies are needed to investigate the potential correlation.

  11. The association between overweight, obesity and ovarian cancer: a meta-analysis.

    PubMed

    Liu, Zhen; Zhang, Ting-Ting; Zhao, Jing-Jing; Qi, Su-Fen; Du, Pei; Liu, Dian-Wu; Tian, Qing-Bao

    2015-12-01

    Epidemiological studies have reported an inconsistent association between obesity and ovarian cancer. To update the current knowledge of and further qualify the association between overweight, obesity and ovarian cancer risk, we conducted a meta-analysis of published observational studies. Using the PubMed, MEDLINE and EMBASE databases, we performed a literature search of all of the case-control and cohort studies published as original articles in English before March 2015. We included 26 observational studies, of which 13 were case-control studies (7782 cases and 21 854 controls) and 13 were cohort studies (5181 cases). Fixed- and random-effects models were used to compute summary estimates and the corresponding 95% confidence intervals. Subgroup analyses were also performed. The pooled relative risk for overweight and obesity compared with normal weight (body mass index = 18.5-24.9 kg/m(2)) was 1.07 (95% confidence interval: 1.02-1.12) and 1.28 (95% confidence interval: 1.16-1.41), respectively. In subgroup analyses, we found that overweight/obesity increased the risk of ovarian cancer in most groups, except for the postmenopausal group (overweight: pooled relative risk = 0.97, 95% confidence interval: 0.76-1.24; obesity: pooled relative risk = 0.93, 95% confidence interval: 0.61-1.42). There was no evidence of publication bias. Increased body weight was associated with an increased risk of ovarian cancer; in particular, severe obesity demonstrated a stronger risk effect. No statistically significant association was observed in the postmenopausal period, but was in the premenopausal period. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Drugs Commonly Associated With Weight Change: A Systematic Review and Meta-analysis

    PubMed Central

    Domecq, Juan Pablo; Prutsky, Gabriela; Leppin, Aaron; Sonbol, M. Bassam; Altayar, Osama; Undavalli, Chaitanya; Wang, Zhen; Elraiyah, Tarig; Brito, Juan Pablo; Mauck, Karen F.; Lababidi, Mohammed H.; Prokop, Larry J.; Asi, Noor; Wei, Justin; Fidahussein, Salman; Montori, Victor M.

    2015-01-01

    Context: Various drugs affect body weight as a side effect. Objective: We conducted this systematic review and meta-analysis to summarize the evidence about commonly prescribed drugs and their association with weight change. Data Sources: MEDLINE, DARE, and the Cochrane Database of Systematic Reviews were searched to identify published systematic reviews as a source for trials. Study Selection: We included randomized trials that compared an a priori selected list of drugs to placebo and measured weight change. Data Extraction: We extracted data in duplicate and assessed the methodological quality using the Cochrane risk of bias tool. Results: We included 257 randomized trials (54 different drugs; 84 696 patients enrolled). Weight gain was associated with the use of amitriptyline (1.8 kg), mirtazapine (1.5 kg), olanzapine (2.4 kg), quetiapine (1.1 kg), risperidone (0.8 kg), gabapentin (2.2 kg), tolbutamide (2.8 kg), pioglitazone (2.6 kg), glimepiride (2.1 kg), gliclazide (1.8 kg), glyburide (2.6 kg), glipizide (2.2 kg), sitagliptin (0.55 kg), and nateglinide (0.3 kg). Weight loss was associated with the use of metformin (1.1 kg), acarbose (0.4 kg), miglitol (0.7 kg), pramlintide (2.3 kg), liraglutide (1.7 kg), exenatide (1.2 kg), zonisamide (7.7 kg), topiramate (3.8 kg), bupropion (1.3 kg), and fluoxetine (1.3 kg). For many other remaining drugs (including antihypertensives and antihistamines), the weight change was either statistically nonsignificant or supported by very low-quality evidence. Conclusions: Several drugs are associated with weight change of varying magnitude. Data are provided to guide the choice of drug when several options exist and institute preemptive weight loss strategies when obesogenic drugs are prescribed. PMID:25590213

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

    PubMed

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

    2015-01-01

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

  14. Pre-eclampsia is associated with, and preceded by, hypertriglyceridaemia: a meta-analysis.

    PubMed

    Gallos, I D; Sivakumar, K; Kilby, M D; Coomarasamy, A; Thangaratinam, S; Vatish, M

    2013-10-01

    Elevated triglycerides are a feature of the metabolic syndrome, maternal obesity, maternal vasculitis (i.e. systemic lupus erythematosus) and diabetes mellitus. These conditions are all known risk factors for pre-eclampsia. Hypertriglyceridaemia therefore may be associated with pre-eclampsia and indeed this may precede the presence of overt disease. In this study we determine the association between hypertriglyceridaemia and pre-eclampsia in pregnant women. We searched MEDLINE, EMBASE, Web of Science, Excerpta Medica Database, ISI Web of Knowledge, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library from inception until June 2012 and reference lists of relevant studies. Two reviewers independently selected studies on pregnant women where triglycerides were measured and women were followed up until the development of pre-eclampsia or selected on the basis of presence of pre-eclampsia and compared with controls. We collected and meta-analysed the weighted mean differences (WMDs) of triglyceride levels from individual studies using a random effects model. We found strong evidence from meta-analysis of 24 case-control studies (2720 women) that pre-eclampsia is associated with higher levels of serum triglycerides (WMD 0.78 mmol/l, 95% confidence interval 0.6-0.96, P < 0.00001). This finding is also confirmed in five cohort studies, that recruited 3147 women in the second trimester before the onset of pre-eclampsia, which proves that hypertriglyceridaemia precedes the onset of pre-eclampsia (WMD 0.24 mmol/l, 95% confidence interval 0.13-0.34, P < 0.0001). Hypertriglyceridaemia is associated with and precedes the onset of pre-eclampsia. Further research should focus on defining the prognostic accuracy of this test to identify women at risk and the beneficial effect of triglyceride-lowering therapies in pregnancy. © 2013 RCOG.

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

    PubMed

    Sulovari, Arvis; Li, Dawei

    2014-07-19

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

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

    PubMed Central

    2014-01-01

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

  17. The associations between VEGF gene polymorphisms and diabetic retinopathy susceptibility: a meta-analysis of 11 case-control studies.

    PubMed

    Han, Liyuan; Zhang, Lina; Xing, Wenhua; Zhuo, Renjie; Lin, XiaLu; Hao, Yanhua; Wu, Qunhong; Zhao, Jinshun

    2014-01-01

    AIMS. Published data on the associations of VEGF polymorphisms with diabetic retinopathy (DR) susceptibility are inconclusive. A systematic meta-analysis was undertaken to clarify this topic. METHODS. Data were collected from the following electronic databases: PubMed, Embase, OVID, Web of Science, Elsevier Science Direct, Excerpta Medica Database (EMBASE), and Cochrane Library with the last report up to January 10, 2014. ORs and 95% CIs were calculated for VEGF-2578C/A (rs699947), -1154G/A (rs1570360), -460T/C (rs833061), -634G>C (rs2010963), and +936C/T (rs3025039) in at least two published studies. Meta-analysis was performed in a fixed/random effect model by using the software STATA 12.0. RESULTS. A total of 11 studies fulfilling the inclusion criteria were included in this meta-analysis. A significant relationship between VEGF+936C/T (rs3025039) polymorphism and DR was found in a recessive model (OR = 3.19, 95% CI = 1.20-8.41, and P(z) = 0.01) in Asian and overall populations, while a significant association was also found between -460T/C (rs833061) polymorphism and DR risk under a recessive model (OR = 2.12, 95% CI = 1.12-4.01, and P(z) = 0.02). CONCLUSIONS. Our meta-analysis demonstrates that +936C/T (rs3025039) is likely to be associated with susceptibility to DR in Asian populations, and the recessive model of -460T/C (rs833061) is associated with elevated DR susceptibility.

  18. 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-ana