Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India.
Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India.
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DOI：
10.2337/db12-1077
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发表时间：
2013-05
期刊：
影响因子：
7.7
通讯作者：
Sanghera DK
中科院分区：
文献类型：
--
作者：
Saxena R;Saleheen D;Been LF;Garavito ML;Braun T;Bjonnes A;Young R;Ho WK;Rasheed A;Frossard P;Sim X;Hassanali N;Radha V;Chidambaram M;Liju S;Rees SD;Ng DP;Wong TY;Yamauchi T;Hara K;Tanaka Y;Hirose H;McCarthy MI;Morris AP;DIAGRAM;MuTHER;AGEN;Basit A;Barnett AH;Katulanda P;Matthews D;Mohan V;Wander GS;Singh JR;Mehra NK;Ralhan S;Kamboh MI;Mulvihill JJ;Maegawa H;Tobe K;Maeda S;Cho YS;Tai ES;Kelly MA;Chambers JC;Kooner JS;Kadowaki T;Deloukas P;Rader DJ;Danesh J;Sanghera DK
我们对来自印度的旁遮普锡克教徒进行了全基因组关联研究(GWAS)和对2型糖尿病(T2D)的多阶段荟萃分析。我们在1,616名个体(842例受试者)中发现GWA，随后在旁遮普锡克教徒(n=2,819；801例受试者)中电子复制了前513个独立单核苷酸多态(−)(P<；10 SNP 3)。我们通过对旁遮普锡克教徒样本(n=2,894；1,711例受试者)进行基因分型，进一步复制了66个SNP(P<；10−4)。在锡克教徒群体(n=7,329；3,354例)的联合Meta分析中，我们发现了一个与13q12处的T2D相关的新基因座，其代表是SGCG基因中一个直接分型的内含子SNP(rs9552911，P=1.82×10−8)。接下来，我们在电子复制(阶段2b)中对29,157名非锡克教徒(10,971例受试者)的前513个信号(P<；10−3)进行了复制，并在10,817名南亚人(5,157例受试者)中进行了多达31个TOP信号(P<；10−4)的从头基因分型(阶段3b)。在合并的南亚荟萃分析中，我们观察到6个提示关联(P<；10−5到<；10−7)，包括位于HMG1L1/CTCFL、PLXNA4、SCAP和chr5p11的SNP。对33,707名东亚人(16,746名病例受试者)(阶段3c)和47,117名欧洲人(8,130名病例受试者)(阶段3)的31个顶级SNPs的进一步评估，以及对来自27个多种族研究的128,127个个体(44,358个病例受试者)的联合荟萃分析，没有发现任何额外的基因座，也没有任何新变异复制的证据。我们的发现为存在与T2D相关的人群特异性信号提供了新的证据，这可能为T2D的发病机制提供更多的见解。
We performed a genome-wide association study (GWAS) and a multistage meta-analysis of type 2 diabetes (T2D) in Punjabi Sikhs from India. Our discovery GWAS in 1,616 individuals (842 case subjects) was followed by in silico replication of the top 513 independent single nucleotide polymorphisms (SNPs) (P < 10−3) in Punjabi Sikhs (n = 2,819; 801 case subjects). We further replicated 66 SNPs (P < 10−4) through genotyping in a Punjabi Sikh sample (n = 2,894; 1,711 case subjects). On combined meta-analysis in Sikh populations (n = 7,329; 3,354 case subjects), we identified a novel locus in association with T2D at 13q12 represented by a directly genotyped intronic SNP (rs9552911, P = 1.82 × 10−8) in the SGCG gene. Next, we undertook in silico replication (stage 2b) of the top 513 signals (P < 10−3) in 29,157 non-Sikh South Asians (10,971 case subjects) and de novo genotyping of up to 31 top signals (P < 10−4) in 10,817 South Asians (5,157 case subjects) (stage 3b). In combined South Asian meta-analysis, we observed six suggestive associations (P < 10−5 to < 10−7), including SNPs at HMG1L1/CTCFL, PLXNA4, SCAP, and chr5p11. Further evaluation of 31 top SNPs in 33,707 East Asians (16,746 case subjects) (stage 3c) and 47,117 Europeans (8,130 case subjects) (stage 3d), and joint meta-analysis of 128,127 individuals (44,358 case subjects) from 27 multiethnic studies, did not reveal any additional loci nor was there any evidence of replication for the new variant. Our findings provide new evidence on the presence of a population-specific signal in relation to T2D, which may provide additional insights into T2D pathogenesis.
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影响因子：
4.4
作者：
Avondo F;Roncaglia P;Crescenzio N;Krmac H;Garelli E;Armiraglio M;Castagnoli C;Campagnoli MF;Ramenghi U;Gustincich S;Santoro C;Dianzani I
通讯作者：
Dianzani I
影响因子：
30.8
作者：
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通讯作者：
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DOI：
10.1083/jcb.142.5.1279
发表时间：
1998-09-07
期刊：
The Journal of cell biology
影响因子：
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作者：
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通讯作者：
McNally EM
全基因组关联研究的荟萃分析确定了东亚人 2 型糖尿病的 8 个新位点
影响因子：
30.8
作者：
Cho, Yoon Shin;Chen, Chien-Hsiun;Hu, Cheng;Long, Jirong;Ong, Rick Twee Hee;Sim, Xueling;Takeuchi, Fumihiko;Wu, Ying;Go, Min Jin;Yamauchi, Toshimasa;Chang, Yi-Cheng;Kwak, Soo Heon;Ma, Ronald C. W.;Yamamoto, Ken;Adair, Linda S.;Aung, Tin;Cai, Qiuyin;Chang, Li-Ching;Chen, Yuan-Tsong;Gao, Yutang;Hu, Frank B.;Kim, Hyung-Lae;Kim, Sangsoo;Kim, Young Jin;Lee, Jeannette Jen-Mai;Lee, Nanette R.;Li, Yun;Liu, Jian Jun;Lu, Wei;Nakamura, Jiro;Nakashima, Eitaro;Ng, Daniel Peng-Keat;Tay, Wan Ting;Tsai, Fuu-Jen;Wong, Tien Yin;Yokota, Mitsuhiro;Zheng, Wei;Zhang, Rong;Wang, Congrong;So, Wing Yee;Ohnaka, Keizo;Ikegami, Hiroshi;Hara, Kazuo;Cho, Young Min;Cho, Nam H.;Chang, Tien-Jyun;Bao, Yuqian;Hedman, Asa K.;Morris, Andrew P.;McCarthy, Mark I.;Takayanagi, Ryoichi;Park, Kyong Soo;Jia, Weiping;Chuang, Lee-Ming;Chan, Juliana C. N.;Maeda, Shiro;Kadowaki, Takashi;Lee, Jong-Young;Wu, Jer-Yuarn;Teo, Yik Ying;Tai, E. Shyong;Shu, Xiao Ou;Mohlke, Karen L.;Kato, Norihiro;Han, Bok-Ghee;Seielstad, Mark
通讯作者：
Seielstad, Mark
DOI：
10.1016/j.numecd.2011.01.006
发表时间：
2012-11
期刊：
Nutrition, metabolism, and cardiovascular diseases : NMCD
影响因子：
--
作者：
Been LF;Hatfield JL;Shankar A;Aston CE;Ralhan S;Wander GS;Mehra NK;Singh JR;Mulvihill JJ;Sanghera DK
通讯作者：
Sanghera DK