Identification of new genetic risk variants for type 2 diabetes.
Identification of new genetic risk variants for type 2 diabetes.
复制标题
DOI：
10.1371/journal.pgen.1001127
复制
发表时间：
2010-09-16
期刊：
影响因子：
4.5
通讯作者：
Hu FB
中科院分区：
文献类型：
--
作者：
Shu XO;Long J;Cai Q;Qi L;Xiang YB;Cho YS;Tai ES;Li X;Lin X;Chow WH;Go MJ;Seielstad M;Bao W;Li H;Cornelis MC;Yu K;Wen W;Shi J;Han BG;Sim XL;Liu L;Qi Q;Kim HL;Ng DP;Lee JY;Kim YJ;Li C;Gao YT;Zheng W;Hu FB
尽管已有20多个2型糖尿病（T2D）的遗传易感位点被报道，但大多数已报道的变异效应较小至中等，仅占T2D遗传度的一小部分，这表明该疾病的大多数个体间遗传变异仍有待确定。我们在亚洲糖尿病联盟内进行了一项多阶段的全基因组关联研究（GWAS），以寻找T2D易感标记物。从对上海中国女性中选取的1019例T2D患者和1710例对照进行基因分型的590887个单核苷酸多态性（SNP）中，我们挑选出与已知T2D位点不存在连锁不平衡（r²<0.2）的前2100个SNP，在针对欧美裔、韩国人和新加坡华人进行的三项T2D GWAS中进行计算机模拟验证。对来自上海的另一组独立的1645例患者和1649例对照对5个最有希望的SNP进行基因分型，其中4个SNP在另外两项中国研究中的1487例患者和3316例对照中进一步进行基因分型。在对9794例患者和14615例对照的联合分析中，发现rs1359790（13q31.1）、rs10906115（10p13）和rs1436955（15q22.2）在所有研究中具有一致的关联性，其P值（每个等位基因的比值比，95%置信区间）分别为6.49×10⁻⁹（1.15，1.10 - 1.20）、1.45×10⁻⁸（1.13，1.08 - 1.18）和7.14×10⁻⁷（1.13，1.08 - 1.19）。我们的研究为13q31.1处的一个新的T2D易感位点以及先前GWAS所报道区域（10p13和15q22.2）附近存在新的独立风险变异提供了有力证据。
2型糖尿病是一种影响全球超过10亿人的复杂疾病，被认为是由环境和遗传因素共同导致的。尽管一些研究表明某些基因可能使一些人比其他人更容易患2型糖尿病，但迄今为止所报道的基因效应较小，且在2型糖尿病病例中所占比例较小。此外，尽管已知亚洲人比生活在西方国家的人更容易出现胰岛素抵抗，且2型糖尿病在亚洲国家的发病率惊人地上升，但这些研究很少在亚洲人群中进行。我们进行了一项涉及9794例2型糖尿病患者和14615例对照（主要为亚洲人）的多阶段研究，以发现与2型糖尿病易感性相关的基因。我们确定了3个与2型糖尿病风险增加相关的遗传区域。
Although more than 20 genetic susceptibility loci have been reported for type 2 diabetes (T2D), most reported variants have small to moderate effects and account for only a small proportion of the heritability of T2D, suggesting that the majority of inter-person genetic variation in this disease remains to be determined. We conducted a multistage, genome-wide association study (GWAS) within the Asian Consortium of Diabetes to search for T2D susceptibility markers. From 590,887 SNPs genotyped in 1,019 T2D cases and 1,710 controls selected from Chinese women in Shanghai, we selected the top 2,100 SNPs that were not in linkage disequilibrium (r2<0.2) with known T2D loci for in silico replication in three T2D GWAS conducted among European Americans, Koreans, and Singapore Chinese. The 5 most promising SNPs were genotyped in an independent set of 1,645 cases and 1,649 controls from Shanghai, and 4 of them were further genotyped in 1,487 cases and 3,316 controls from 2 additional Chinese studies. Consistent associations across all studies were found for rs1359790 (13q31.1), rs10906115 (10p13), and rs1436955 (15q22.2) with P-values (per allele OR, 95%CI) of 6.49×10−9 (1.15, 1.10–1.20), 1.45×10−8 (1.13, 1.08–1.18), and 7.14×10−7 (1.13, 1.08–1.19), respectively, in combined analyses of 9,794 cases and 14,615 controls. Our study provides strong evidence for a novel T2D susceptibility locus at 13q31.1 and the presence of new independent risk variants near regions (10p13 and 15q22.2) reported by previous GWAS. Type 2 diabetes, a complex disease affecting more than a billion people worldwide, is believed to be caused by both environmental and genetic factors. Although some studies have shown that certain genes may make some people more susceptible to type 2 diabetes than others, the genes reported to date have only a small effect and account for a small proportion of type 2 diabetes cases. Furthermore, few of these studies have been conducted in Asian populations, although Asians are known to be more susceptible to insulin resistance than people living in Western countries, and incidence of type 2 diabetes has been increasing alarmingly in Asian countries. We conducted a multi-stage study involving 9,794 type 2 diabetes cases and 14,615 controls, predominantly Asians, to discover genes related to susceptibility to type 2 diabetes. We identified 3 genetic regions that are related to increased risk of type 2 diabetes.
登录
查看更多内容
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
影响因子：
4.3
作者：
King, George L.
通讯作者：
King, George L.
影响因子：
5.8
作者：
Yanai, I;Benjamin, H;Shmueli, O
通讯作者：
Shmueli, O
DOI：
10.1016/j.bbrc.2008.08.037
发表时间：
2008-10-24
影响因子：
3.1
作者：
Ding, Wei;Warburton, David
通讯作者：
Warburton, David
影响因子：
4.5
作者：
Tsai FJ;Yang CF;Chen CC;Chuang LM;Lu CH;Chang CT;Wang TY;Chen RH;Shiu CF;Liu YM;Chang CC;Chen P;Chen CH;Fann CS;Chen YT;Wu JY
通讯作者：
Wu JY