A genome-wide association study in American Indians implicates DNER as a susceptibility locus for type 2 diabetes.
A genome-wide association study in American Indians implicates DNER as a susceptibility locus for type 2 diabetes.
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作者：
Hanson RL;Muller YL;Kobes S;Guo T;Bian L;Ossowski V;Wiedrich K;Sutherland J;Wiedrich C;Mahkee D;Huang K;Abdussamad M;Traurig M;Weil EJ;Nelson RG;Bennett PH;Knowler WC;Bogardus C;Baier LJ
大多数与2型糖尿病（T2 DM）相关的遗传变异已通过欧洲人的全基因组关联研究（GWAS）确定。本研究报告了美国印第安人中初发T2 DM的GWAS。参与者选自在皮马印第安人中进行的纵向研究，包括278例25岁之前发病的糖尿病患者，295例≥45岁的非糖尿病对照，以及267例病例或对照的兄弟姐妹。个体基因分型在一个1 M单核苷酸多态性（SNP）阵列，导致453，654个SNP与次要等位基因频率>0.05。分析SNPs在病例和对照中的关联，并进行基于家族的关联检验。从499个与糖尿病相关的SNP中选择标签SNP（n = 311）（病例对照分析中P < 0.0005或基于家族的分析中P < 0.0003），并在多达6，834名额外的皮马印第安人中对这些SNP进行基因分型以评估复制。DNER中的Rs 1861612与T2 DM相关（比值比= 1.29/T等位基因拷贝; P = 6.6 × 10−8，这代表了全基因组显著性，占分析的有效独立SNP的数量）。小鼠胰腺β细胞中的转染研究表明，DNER调节notch信号通路基因的表达。这些研究暗示DNER是美洲印第安人T2 DM的易感基因。
Most genetic variants associated with type 2 diabetes mellitus (T2DM) have been identified through genome-wide association studies (GWASs) in Europeans. The current study reports a GWAS for young-onset T2DM in American Indians. Participants were selected from a longitudinal study conducted in Pima Indians and included 278 cases with diabetes with onset before 25 years of age, 295 nondiabetic controls ≥45 years of age, and 267 siblings of cases or controls. Individuals were genotyped on a ∼1M single nucleotide polymorphism (SNP) array, resulting in 453,654 SNPs with minor allele frequency >0.05. SNPs were analyzed for association in cases and controls, and a family-based association test was conducted. Tag SNPs (n = 311) were selected for 499 SNPs associated with diabetes (P < 0.0005 in case-control analyses or P < 0.0003 in family-based analyses), and these SNPs were genotyped in up to 6,834 additional Pima Indians to assess replication. Rs1861612 in DNER was associated with T2DM (odds ratio = 1.29 per copy of the T allele; P = 6.6 × 10−8, which represents genome-wide significance accounting for the number of effectively independent SNPs analyzed). Transfection studies in murine pancreatic β-cells suggested that DNER regulates expression of notch signaling pathway genes. These studies implicate DNER as a susceptibility gene for T2DM in American Indians.
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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
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
影响因子：
7.7
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
通讯作者：
Sanghera DK
影响因子：
7.7
作者：
Hanson RL;Guo T;Muller YL;Fleming J;Knowler WC;Kobes S;Bogardus C;Baier LJ
通讯作者：
Baier LJ
影响因子：
7.7
作者：
Rong R;Hanson RL;Ortiz D;Wiedrich C;Kobes S;Knowler WC;Bogardus C;Baier LJ
通讯作者：
Baier LJ