Nat Genet. 2011 Dec 11;44(1):67-72. doi: 10.1038/ng.1019.
Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
Cho YS,
Chen CH,
Hu C,
Long J,
Ong RT,
Sim X,
Takeuchi F,
Wu Y,
Go MJ,
Yamauchi T,
Chang YC,
Kwak SH,
Ma RC,
Yamamoto K,
Adair LS,
Aung T,
Cai Q,
Chang LC,
Chen YT,
Gao Y,
Hu FB,
Kim HL,
Kim S,
Kim YJ,
Lee JJ,
Lee NR,
Li Y,
Liu JJ,
Lu W,
Nakamura J,
Nakashima E,
Ng DP,
Tay WT,
Tsai FJ,
Wong TY,
Yokota M,
Zheng W,
Zhang R,
Wang C,
So WY,
Ohnaka K,
Ikegami H,
Hara K,
Cho YM,
Cho NH,
Chang TJ,
Bao Y,
Hedman ÅK,
Morris AP,
McCarthy MI;
DIAGRAM Consortium;
MuTHER Consortium,
Takayanagi R,
Park KS,
Jia W,
Chuang LM,
Chan JC,
Maeda S,
Kadowaki T,
Lee JY,
Wu JY,
Teo YY,
Tai ES,
Shu XO,
Mohlke KL,
Kato N,
Han BG,
Seielstad M.
Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, McCullch LJ, Ferreira T, Grallert H, Amin N, Wu G, Willer CJ, Raychaudhuri S, McCarroll SA, Langenberg C, Hofmann OM, Dupuis J, Qi L, Segrè AV, van Hoek M, Navarro P, Ardlie K, Balkau B, Benediktsson R, Bennett AJ, Blagieva R, Boerwinkle E, Bonnycastle LL, Boström KB, Bravenboer B, Bumpstead S, Burtt NP, Charpentier G, Chines PS, Cornelis M, Couper DJ, Crawford G, Doney AS, Elliott KS, Elliott AL, Erdos MR, Fox CS, Franklin CS, Ganser M, Gieger C, Grarup N, Green T, Griffin S, Groves CJ, Guiducci C, Hadjadj S, assanali N, Herder C, Isomaa B, Jackson AU, Johnson PR, Jørgensen T, Kao WH, Klopp N, Kong A, Kraft P, Kuusisto J, Lauritzen T, Li M, Lieverse A, Lindgren CM, Lyssenko V, Marre M, Meitinger T, Midthjell K, Morken MA, Narisu N, Nilsson P, Owen KR, Payne F, Perry JR, Petersen AK, Platou C, Proença C, Prokopenko I, Rathmann W, Rayner NW, Robertson NR, Rocheleau G, Roden M, Sampson MJ, Saxena R, Shields BM, Shrader P, Sigurdsson G, Sparsø T, Strassburger K, Stringham HM, Sun Q, Swift AJ, Thorand B, Tichet J, Tuomi T, van Dam RM, van Haeften TW, van Herpt T, van Vliet-Ostaptchouk JV, Walters GB, Weedon MN, Wijmenga C, Witteman J, Bergman RN, Cauchi S, Collins FS, Gloyn AL, Gyllensten U, Hansen T, Hide WA, Hitman GA, Hofman A, Hunter DJ, Hveem K, Laakso M, Mohlke KL, Morris AD, Palmer CN, Pramstaller PP, Rudan I, Sijbrands E, Stein LD, Tuomilehto J, Uitterlinden A, Walker M, Wareham NJ, Watanabe RM, Abecasis GR, Boehm BO, Campbell H, Daly MJ, Hattersley AT, Hu FB, Meigs JB, Pankow JS, Pedersen O, Wichmann HE, Barroso I, Florez JC, Frayling TM, Groop L, Sladek R, Thorsteinsdottir U, Wilson JF, Illig T, Froguel P, van Duijn CM, Stefansson K, Altshuler D, Boehnke M, McCarthy MI, Ahmadi K, Ainali C, Barrett A, Bataille V, Bell JT, Buil A, Deloukas P, Dermitzakis ET, Dimas A, Durbin R, Glass D, Grundberg E, Hammond C, Hassanali N, Hedman ÅK, Ingle C, Knowles D, Krestyaninova M, Lindgren C, Lowe C, McCarthy MI, di Meglio P, Montgomery S, Nestle F, Nica AC, Nisbet J, O'Rahilly S, Parts L, Potter S, Sekowska M, Shin SY, Small KS, Soranzo N, Spector TD, Surdulescu G, Travers M, Tsoka S, Tsaprouni L, Wilk A, Yang TP, Zondervan KT.
Source
Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Cheongwon-gun, Gangoe-myeon, Yeonje-ri, Korea. yooncho33@korea.kr
Abstract
We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
- PMID:
- 22158537
- [PubMed - indexed for MEDLINE]
- PMCID:
- PMC3582398
Free PMC ArticleFigure 1Genome-wide Manhattan plot for the EA T2D stage 1 meta-analysis
−log10(P-values) using the trend test are shown for SNPs distributed across the entire autosomal genome. Red dots at each locus indicate the signals with P-value <10−6 detected in the genome-wide meta-analysis. A total of 1,934,619 SNPs that were present in ≥5 stage 1 studies were used to generate both plots.
Nat Genet. 2011 December 11;44(1):67-72.
Figure 2Regional association plots for new T2D loci
The upper panel indicates the positions of SNPs and the middle panel, shows regional association results from the genome-wide meta-analysis. The trend test −log10(P-values) are shown for SNPs distributed in a 0.8 Mb genomic region centered on the most strongly associated signal, which is depicted as a purple diamond in the stage 1 results and a red diamond for the combined stage 1+2+3 results. The lower panel shows the locations of known genes in the region. Genetic information is taken from Human Genome build hg18 and LD structure was based on 1000 Genomes (June 2010) HapMap JPT+CHB.
Nat Genet. 2011 December 11;44(1):67-72.
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