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Diabetes. 2013 May;62(5):1746-55. doi: 10.2337/db12-1077. Epub 2013 Jan 8.

Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India.

Collaborators (265)

Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, McCulloch LJ, Ferreira T, Grallert H, Amin N, Wu G, Willer CJ, Raychaudhuri S, McCarroll SA, Langenberg C, Hofmann OM, Dupuis J, Qi L, VSegrè A, 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, Hassanali 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 KR, Ainali C, Barrett A, Bataille V, Bell JT, Buil A, Deloukas P, Dermitzakis ET, Dimas AS, Durbin R, Glass D, Grundberg E, Hassanali N, Hedman ÅK, Ingle C, Knowles D, Keildson S, Krestyaninova M, Lindgren CM, Lowe CE, McCarthy MI, Meduri E, Meglio Pd, Min JL, Montgomery SB, Nestle FO, Nica AC, Nisbet J, O'Rahilly S, Parts L, Potter S, Sekowska M, Shin SY, Small KS, Soranzo N, Spector TD, Surdulescu G, Travers ME, Tsaprouni L, Tsoka S, Wilk A, Yang TP, Zondervan KT, Cho YS, Chen CH, Hu C, Long J, Ong RT, Sim X, Takeuchi F, Wu Y, Jin Go M, 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, Jen-Mai Lee J, Lee NR, Li Y, Liu JJ, Lu W, Nakamura J, Nakashima E, Peng-Keat Ng D, Tay WT, Tsai FJ, Yin Wong T, Yokota M, Zheng W, Zhang R, Wang C, Yee So W, Ohnaka K, Ikegami H, Hara K, Cho YM, Cho NH, Chang TJ, Bao Y, Hedman ÅK, 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.

Author information

1
Center for Human Genetic Research and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

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.

PMID:
23300278
PMCID:
PMC3636649
DOI:
10.2337/db12-1077
[Indexed for MEDLINE]
Free PMC Article

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