A genome-wide association study of type 2 diabetes in finns detects multiple susceptibility variants

Laura J. Scott; Karen L. Mohlke; Lori L. Bonnycastle; Cristen J. Willer; Yun Li; William L. Duren; Michael R. Erdos; Heather M. Stringham; Peter S. Chines; Anne U. Jackson; Ludmila Prokunina-Olsson; Chia Jen Ding; Amy J. Swift; Narisu; Tianle Hu; Randall Pruim; Rui Xiao; Xiao Yi Li; Karen N. Conneely; Nancy L. Riebow; Andrew G. Sprau; Maurine Tong; Peggy P. White; Kurt N. Hetrick; Michael W. Barnhart; Craig W. Bark; Janet L. Goldstein; Lee Watkins; Fang Xiang; Jouko Saramies; Thomas A. Buchanan; Richard M. Watanabe; Timo T. Valle; Leena Kinnunen; Gonçalo R. Abecasis; Elizabeth W. Pugh; Kimberly F. Doheny; Richard N. Bergman; Jaakko Tuomilehto; Francis S. Collins; Michael Boehnke

doi:10.1126/science.1142382

A genome-wide association study of type 2 diabetes in finns detects multiple susceptibility variants

Laura J. Scott, Karen L. Mohlke, Lori L. Bonnycastle, Cristen J. Willer, Yun Li, William L. Duren, Michael R. Erdos, Heather M. Stringham, Peter S. Chines, Anne U. Jackson, Ludmila Prokunina-Olsson, Chia Jen Ding, Amy J. Swift, Narisu, Tianle Hu, Randall Pruim, Rui Xiao, Xiao Yi Li, Karen N. Conneely, Nancy L. RiebowAndrew G. Sprau, Maurine Tong, Peggy P. White, Kurt N. Hetrick, Michael W. Barnhart, Craig W. Bark, Janet L. Goldstein, Lee Watkins, Fang Xiang, Jouko Saramies, Thomas A. Buchanan, Richard M. Watanabe, Timo T. Valle, Leena Kinnunen, Gonçalo R. Abecasis, Elizabeth W. Pugh, Kimberly F. Doheny, Richard N. Bergman, Jaakko Tuomilehto, Francis S. Collins, Michael Boehnke

School of Medicine

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2042 Scopus citations

Abstract

Identifying the genetic variants that increase the risk of type 2 diabetes (T2D) in humans has been a formidable challenge. Adopting a genome-wide association strategy, we genotyped 1161 Finnish T2D cases and 1174 Finnish normal glucose-tolerant (NGT) controls with >315,000 single-nucleotide polymorphisms (SNPs) and imputed genotypes for an additional >2 million autosomal SNPs. We carried out association analysis with these SNPs to identify genetic variants that predispose to T2D, compared our T2D association results with the results of two similar studies, and genotyped 80 SNPs in an additional 1215 Finnish T2D cases and 1258 Finnish NGT controls. We identify T2D-associated variants in an intergenic region of chromosome 11p12, contribute to the identification of T2D-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk. This brings the number of T2D loci now confidently identified to at least 10.

Original language	English (US)
Pages (from-to)	1341-1345
Number of pages	5
Journal	Science
Volume	316
Issue number	5829
DOIs	https://doi.org/10.1126/science.1142382
State	Published - Jun 1 2007

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Scott, L. J., Mohlke, K. L., Bonnycastle, L. L., Willer, C. J., Li, Y., Duren, W. L., Erdos, M. R., Stringham, H. M., Chines, P. S., Jackson, A. U., Prokunina-Olsson, L., Ding, C. J., Swift, A. J., Narisu, Hu, T., Pruim, R., Xiao, R., Li, X. Y., Conneely, K. N., ... Boehnke, M. (2007). A genome-wide association study of type 2 diabetes in finns detects multiple susceptibility variants. Science, 316(5829), 1341-1345. https://doi.org/10.1126/science.1142382

Scott, LJ, Mohlke, KL, Bonnycastle, LL, Willer, CJ, Li, Y, Duren, WL, Erdos, MR, Stringham, HM, Chines, PS, Jackson, AU, Prokunina-Olsson, L, Ding, CJ, Swift, AJ, Narisu, Hu, T, Pruim, R, Xiao, R, Li, XY, Conneely, KN, Riebow, NL, Sprau, AG, Tong, M, White, PP, Hetrick, KN, Barnhart, MW, Bark, CW, Goldstein, JL, Watkins, L, Xiang, F, Saramies, J, Buchanan, TA, Watanabe, RM, Valle, TT, Kinnunen, L, Abecasis, GR, Pugh, EW, Doheny, KF, Bergman, RN, Tuomilehto, J, Collins, FS & Boehnke, M 2007, 'A genome-wide association study of type 2 diabetes in finns detects multiple susceptibility variants', Science, vol. 316, no. 5829, pp. 1341-1345. https://doi.org/10.1126/science.1142382

@article{0af2181752e847d78607fa439b018b93,

title = "A genome-wide association study of type 2 diabetes in finns detects multiple susceptibility variants",

abstract = "Identifying the genetic variants that increase the risk of type 2 diabetes (T2D) in humans has been a formidable challenge. Adopting a genome-wide association strategy, we genotyped 1161 Finnish T2D cases and 1174 Finnish normal glucose-tolerant (NGT) controls with >315,000 single-nucleotide polymorphisms (SNPs) and imputed genotypes for an additional >2 million autosomal SNPs. We carried out association analysis with these SNPs to identify genetic variants that predispose to T2D, compared our T2D association results with the results of two similar studies, and genotyped 80 SNPs in an additional 1215 Finnish T2D cases and 1258 Finnish NGT controls. We identify T2D-associated variants in an intergenic region of chromosome 11p12, contribute to the identification of T2D-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk. This brings the number of T2D loci now confidently identified to at least 10.",

author = "Scott, {Laura J.} and Mohlke, {Karen L.} and Bonnycastle, {Lori L.} and Willer, {Cristen J.} and Yun Li and Duren, {William L.} and Erdos, {Michael R.} and Stringham, {Heather M.} and Chines, {Peter S.} and Jackson, {Anne U.} and Ludmila Prokunina-Olsson and Ding, {Chia Jen} and Swift, {Amy J.} and Narisu and Tianle Hu and Randall Pruim and Rui Xiao and Li, {Xiao Yi} and Conneely, {Karen N.} and Riebow, {Nancy L.} and Sprau, {Andrew G.} and Maurine Tong and White, {Peggy P.} and Hetrick, {Kurt N.} and Barnhart, {Michael W.} and Bark, {Craig W.} and Goldstein, {Janet L.} and Lee Watkins and Fang Xiang and Jouko Saramies and Buchanan, {Thomas A.} and Watanabe, {Richard M.} and Valle, {Timo T.} and Leena Kinnunen and Abecasis, {Gon{\c c}alo R.} and Pugh, {Elizabeth W.} and Doheny, {Kimberly F.} and Bergman, {Richard N.} and Jaakko Tuomilehto and Collins, {Francis S.} and Michael Boehnke",

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doi = "10.1126/science.1142382",

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T1 - A genome-wide association study of type 2 diabetes in finns detects multiple susceptibility variants

AU - Scott, Laura J.

AU - Mohlke, Karen L.

AU - Bonnycastle, Lori L.

AU - Willer, Cristen J.

AU - Li, Yun

AU - Duren, William L.

AU - Erdos, Michael R.

AU - Stringham, Heather M.

AU - Chines, Peter S.

AU - Jackson, Anne U.

AU - Prokunina-Olsson, Ludmila

AU - Ding, Chia Jen

AU - Swift, Amy J.

AU - Narisu,

AU - Hu, Tianle

AU - Pruim, Randall

AU - Xiao, Rui

AU - Li, Xiao Yi

AU - Conneely, Karen N.

AU - Riebow, Nancy L.

AU - Sprau, Andrew G.

AU - Tong, Maurine

AU - White, Peggy P.

AU - Hetrick, Kurt N.

AU - Barnhart, Michael W.

AU - Bark, Craig W.

AU - Goldstein, Janet L.

AU - Watkins, Lee

AU - Xiang, Fang

AU - Saramies, Jouko

AU - Buchanan, Thomas A.

AU - Watanabe, Richard M.

AU - Valle, Timo T.

AU - Kinnunen, Leena

AU - Abecasis, Gonçalo R.

AU - Pugh, Elizabeth W.

AU - Doheny, Kimberly F.

AU - Bergman, Richard N.

AU - Tuomilehto, Jaakko

AU - Collins, Francis S.

AU - Boehnke, Michael

PY - 2007/6/1

Y1 - 2007/6/1

N2 - Identifying the genetic variants that increase the risk of type 2 diabetes (T2D) in humans has been a formidable challenge. Adopting a genome-wide association strategy, we genotyped 1161 Finnish T2D cases and 1174 Finnish normal glucose-tolerant (NGT) controls with >315,000 single-nucleotide polymorphisms (SNPs) and imputed genotypes for an additional >2 million autosomal SNPs. We carried out association analysis with these SNPs to identify genetic variants that predispose to T2D, compared our T2D association results with the results of two similar studies, and genotyped 80 SNPs in an additional 1215 Finnish T2D cases and 1258 Finnish NGT controls. We identify T2D-associated variants in an intergenic region of chromosome 11p12, contribute to the identification of T2D-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk. This brings the number of T2D loci now confidently identified to at least 10.

AB - Identifying the genetic variants that increase the risk of type 2 diabetes (T2D) in humans has been a formidable challenge. Adopting a genome-wide association strategy, we genotyped 1161 Finnish T2D cases and 1174 Finnish normal glucose-tolerant (NGT) controls with >315,000 single-nucleotide polymorphisms (SNPs) and imputed genotypes for an additional >2 million autosomal SNPs. We carried out association analysis with these SNPs to identify genetic variants that predispose to T2D, compared our T2D association results with the results of two similar studies, and genotyped 80 SNPs in an additional 1215 Finnish T2D cases and 1258 Finnish NGT controls. We identify T2D-associated variants in an intergenic region of chromosome 11p12, contribute to the identification of T2D-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk. This brings the number of T2D loci now confidently identified to at least 10.

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A genome-wide association study of type 2 diabetes in finns detects multiple susceptibility variants

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