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

作者信息

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

机构信息

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.

出版信息

Science. 2007 Jun 1;316(5829):1341-5. doi: 10.1126/science.1142382. Epub 2007 Apr 26.

DOI:10.1126/science.1142382
PMID:17463248
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3214617/
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.

摘要

相似文献

[1]
A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.

Science. 2007-6-1

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[9]
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[10]
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本文引用的文献

[1]
Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.

Science. 2007-6-1

[2]
Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.

Science. 2007-6-1

[3]
A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity.

Science. 2007-5-11

[4]
A genome-wide association study identifies novel risk loci for type 2 diabetes.

Nature. 2007-2-22

[5]
The regulation of INK4/ARF in cancer and aging.

Cell. 2006-10-20

[6]
In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion.

J Cell Sci. 2006-10-15

[7]
Inhibition of cyclin-dependent kinase 5 activity protects pancreatic beta cells from glucotoxicity.

J Biol Chem. 2006-9-29

[8]
Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes.

Nat Genet. 2006-3

[9]
Cross-sectional evaluation of the Finnish Diabetes Risk Score: a tool to identify undetected type 2 diabetes, abnormal glucose tolerance and metabolic syndrome.

Diab Vasc Dis Res. 2005-5

[10]
Zinc-ligand interactions modulate assembly and stability of the insulin hexamer -- a review.

Biometals. 2005-8

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