Comprehensive Association Study of Type 2 Diabetes and Related Quantitative Traits With 222 Candidate Genes

被引：93

作者：

Gaulton, Kyle J. ^{[1
]}

Willer, Cristen J. ^{[2
,3
]}

Li, Yun ^{[2
,3
]}

Scott, Laura J. ^{[2
,3
]}

Conneely, Karen N. ^{[2
,3
]}

Jackson, Anne U. ^{[2
,3
]}

Duren, William L. ^{[2
,3
]}

Chines, Peter S. ^{[4
]}

Narisu, Narisu ^{[4
]}

Bonnycastle, Lori L. ^{[4
]}

Luo, Jingchun ^{[5
]}

Tong, Maurine ^{[4
]}

Sprau, Andrew G. ^{[4
]}

Pugh, Elizabeth W. ^{[6
]}

Doheny, Kimberly F. ^{[6
]}

Valle, Timo T. ^{[8
]}

Abecasis, Goncalo R. ^{[2
,3
]}

Tuomilehto, Jaakko ^{[7
,8
,10
]}

Bergman, Richard N. ^{[9
]}

Collins, Francis S. ^{[4
]}

Boehnke, Michael ^{[2
,3
]}

Mohlkel, Karen L. ^{[1
]}

机构：

[1] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA

[2] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[4] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA

[5] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[6] Johns Hopkins Sch Med, Inst Med Genet, Ctr Inherited Dis Res, Baltimore, MD USA

[7] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland

[8] Natl Publ Hlth Inst, Diabet & Genet Epidemiol Unit, Dept Epidemiol & Hlth Promot, Helsinki, Finland

[9] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA

[10] S Ostrobothnia Cent Hosp, Seinajoki, Finland

来源：

DIABETES | 2008年 / 57卷 / 11期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.2337/db07-1731

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVE-Type 2 diabetes is a common complex disorder with environmental and genetic components. We used a candidate gene-based approach to identify single nucleotide polymorphism (SNP) variants in 222 candidate genes that influence susceptibility to type 2 diabetes. RESEARCH DESIGN AND METHODS-In a case-control study of 1,161 type 2 diabetic subjects and 1,174 control Finns who are normal glucose tolerant, we genotyped 3,531 tagSNPs and annotation-based SNPs and imputed an additional 7,498 SNPs, providing 99.9% coverage of common HapMap variants in the 222 candidate genes. Selected SNPs were genotyped in an additional 1,211 type 2 diabetic case subjects and 1,259 control subjects who are normal glucose tolerant, also from Finland. RESULTS-Using SNP- and gene-based analysis methods, we replicated previously reported SNP-type 2 diabetes associations in PPARG, KCNJ11, and SLC2A2; identified significant SNPs in genes with previously reported associations (ENPP1 [rs2021966, P = 0.00026] and NRF1 [rs1882095, P = 0.00096]); and implicated novel genes, including RAPGEF1 (rs4740283, P = 0.00013) and TP53 (rs1042522, Arg72Pro, P = 0.00086), in type 2 diabetes susceptibility. CONCLUSIONS-Our study provides an effective gene-based approach to association study design and analysis. One or more of the newly implicated genes may contribute to type 2 diabetes pathogenesis. Analysis of additional samples will be necessary to determine their effect on susceptibility. Diabetes 57:31363144,2008

引用

页码：3136 / 3144

页数：9

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