Underlying genetic models of inheritance in established type 2 diabetes associations.
Underlying genetic models of inheritance in established type 2 diabetes associations.
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DOI：
10.1093/aje/kwp145
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发表时间：
2009-09-01
影响因子：
5
通讯作者：
Ioannidis JP
中科院分区：
文献类型：
--
作者：
Salanti G;Southam L;Altshuler D;Ardlie K;Barroso I;Boehnke M;Cornelis MC;Frayling TM;Grallert H;Grarup N;Groop L;Hansen T;Hattersley AT;Hu FB;Hveem K;Illig T;Kuusisto J;Laakso M;Langenberg C;Lyssenko V;McCarthy MI;Morris A;Morris AD;Palmer CN;Payne F;Platou CG;Scott LJ;Voight BF;Wareham NJ;Zeggini E;Ioannidis JP
对于大多数常见多态性与常见疾病的关联，遗传的遗传模式是未知的。我们扩展并应用了贝叶斯荟萃分析方法，分析了19项研究中17项与2型糖尿病相关的数据。对于13个多态性，数据符合加性模型，对于4个多态性，数据符合加性或显性模型，对于2个多态性，数据符合加性或隐性遗传模型。在排除了通过代理标记间接检查索引多态性的数据后，使用不同的先验和结果是稳健的。贝叶斯元分析模型得出的遗传效应的点估计与先前基于固定或随机效应模型的报告非常相似，但其中一些影响的不确定性要大得多。我们还检查了遗传模型中研究间异质性的程度，发现遗传模型参数的研究间偏差通常很小。4个snp不能排除杂种优势。关于强复制gwa衍生关联信号的遗传模型的信息可能有助于预测建模，以及设计生物学和功能实验。
For most associations of common polymorphisms with common diseases, the genetic model of inheritance is unknown. We extended and applied a Bayesian meta-analysis approach to data from 19 studies on 17 replicated associations for type 2 diabetes. For 13 polymorphisms, the data fit very well to an additive model, for 4 polymorphisms the data were consistent with either an additive or dominant model, and for 2 polymorphisms with an additive or recessive model of inheritance for the diabetes risk allele. Results were robust to using different priors and after excluding data where index polymorphisms had been examined indirectly through proxy markers. The Bayesian meta-analysis model yielded point estimates for the genetic effects that are very similar to those previously reported based on fixed or random effects models, but uncertainty about several of the effects was substantially larger. We also examined the extent of between-study heterogeneity in the genetic model and found generally small values of the between-study deviation for the genetic model parameter. Heterosis could not be excluded in 4 SNPs. Information on the genetic model of robustly replicated GWA-derived association signals may be useful for predictive modeling, and for designing biological and functional experiments.
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影响因子：
30.8
作者：
Zeggini, Eleftheria;Scott, Laura J.;Saxena, Richa;Voight, Benjamin F.;Marchini, Jonathan L.;Hu, Tianle;de Bakker, Paul I. W.;Abecasis, Goncalo R.;Almgren, Peter;Andersen, Gitte;Ardlie, Kristin;Bostroem, Kristina Bengtsson;Bergman, Richard N.;Bonnycastle, Lori L.;Borch-Johnsen, Knut;Burtt, Noel P.;Chen, Hong;Chines, Peter S.;Daly, Mark J.;Deodhar, Parimal;Ding, Chia-Jen;Doney, Alex S. F.;Duren, William L.;Elliott, Katherine S.;Erdos, Michael R.;Frayling, Timothy M.;Freathy, Rachel M.;Gianniny, Lauren;Grallert, Harald;Grarup, Niels;Groves, Christopher J.;Guiducci, Candace;Hansen, Torben;Herder, Christian;Hitman, Graham A.;Hughes, Thomas E.;Isomaa, Bo;Jackson, Anne U.;Jorgensen, Torben;Kong, Augustine;Kubalanza, Kari;Kuruvilla, Finny G.;Kuusisto, Johanna;Langenberg, Claudia;Lango, Hana;Lauritzen, Torsten;Li, Yun;Lindgren, Cecilia M.;Lyssenko, Valeriya;Marvelle, Amanda F.;Meisinger, Christa;Midthjell, Kristian;Mohlke, Karen L.;Morken, Mario A.;Morris, Andrew D.;Narisu, Narisu;Nilsson, Peter;Owen, Katharine R.;Palmer, Colin N. A.;Payne, Felicity;Perry, John R. B.;Pettersen, Elin;Platou, Carl;Prokopenko, Inga;Qi, Lu;Qin, Li;Rayner, Nigel W.;Rees, Matthew;Roix, Jeffrey J.;Sandbaek, Anelli;Shields, Beverley;Sjogren, Marketa;Steinthorsdottir, Valgerdur;Stringham, Heather M.;Swift, Amy J.;Thorleifsson, Gudmar;Thorsteinsdottir, Unnur;Timpson, Nicholas J.;Tuomi, Tiinamaija;Tuomilehto, Jaakko;Walker, Mark;Watanabe, Richard M.;Weedon, Michael N.;Willer, Cristen J.;Illig, Thomas;Hveem, Kristian;Hu, Frank B.;Laakso, Markku;Stefansson, Kari;Pedersen, Oluf;Wareham, Nicholas J.;Barroso, Ines;Hattersley, Andrew T.;Collins, Francis S.;Groop, Leif;McCarthy, Mark I.;Boehnke, Michael;Altshuler, David
通讯作者：
Altshuler, David
评估18种常见遗传变异的综合遗传变异对2型糖尿病风险的综合影响。
影响因子：
7.7
作者：
Lango H;UK Type 2 Diabetes Genetics Consortium;Palmer CN;Morris AD;Zeggini E;Hattersley AT;McCarthy MI;Frayling TM;Weedon MN
通讯作者：
Weedon MN
影响因子：
5.4
作者：
Seminara, Daniela;Khoury, Muin J.;Ioannidis, John P. A.
通讯作者：
Ioannidis, John P. A.
DOI：
10.1126/science.1142364
发表时间：
2007-06-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Zeggini E;Weedon MN;Lindgren CM;Frayling TM;Elliott KS;Lango H;Timpson NJ;Perry JR;Rayner NW;Freathy RM;Barrett JC;Shields B;Morris AP;Ellard S;Groves CJ;Harries LW;Marchini JL;Owen KR;Knight B;Cardon LR;Walker M;Hitman GA;Morris AD;Doney AS;Wellcome Trust Case Control Consortium (WTCCC);McCarthy MI;Hattersley AT
通讯作者：
Hattersley AT
影响因子：
56.9
作者：
Scott, Laura J.;Mohlke, Karen L.;Boehnke, Michael
通讯作者：
Boehnke, Michael