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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 &gt;315,000 single-nucleotide polymorphisms (SNPs) and imputed genotypes for an additional &gt;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.

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

Genetic factors play an important role in modulating the vulnerability to body mass index (BMI). The purpose of this study is to identify novel genetic variants for BMI using genome-wide association (GWA) meta-analysis.

A novel locus for body mass index on 5p15.2: a meta-analysis of two genome-wide association studies.

New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D-in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1-and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.

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

The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8. Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes.

Title	PMID	PMCID	Public Release Type	Publication Year	DOI	Study Acronym	Public Release Origin
A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.	17463248	PMC3214617	Journal	2007	10.1126/science.1142382	FUSION	Contributing Study
A novel locus for body mass index on 5p15.2: a meta-analysis of two genome-wide association studies.	22446040		Journal	2012	10.1016/j.gene.2012.03.046	FUSION	Contributing Study
Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.	17463246		Journal	2007	10.1126/science.1142358	FUSION	Contributing Study
Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.	17463249	PMC3772310	Journal	2007	10.1126/science.1142364	FUSION	Contributing Study

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