Type 2 diabetes (T2D) is a common, polygenic chronic disease with high heritability. The purpose of this whole-genome association study was to discover novel T2D-associated genes. We genotyped 500 familial cases and 497 controls with >300,000 HapMap-derived tagging single-nucleotide-polymorphism (SNP) markers. When a stringent statistical correction for multiple testing was used, the only significant SNP was at TCF7L2, which has already been discovered and confirmed as a T2D-susceptibility gene. For a replication study, we selected 10 SNPs in six chromosomal regions with the strongest association (singly or as part of a haplotype) for retesting in an independent case-control set including 2,573 T2D cases and 2,776 controls. The most significant replicated result was found at the AHI1-LOC441171 gene region.
Bibliographical noteFunding Information:
We thank the personnel of Oy Jurilab, all participating institutes, the former employees and clinical collaborators of IDgene Pharmaceuticals, Stephane Lobbens for technical assistance, and the subjects who donated samples for this study. This work was partially funded by support from the Finnish Funding Agency for Technology and Innovation (TEKES), to Oy Jurilab. The Study of Health in Pomerania is funded by grant 01ZZ96030 from the German Ministry for Education and Research and by grants from the Ministry for Education, Research, and Cultural Affairs and the Ministry for Social Affairs of the Federal State of Mecklenburg, West Pomerania. The collection of the Dyne-Steel DNA bank for cognitive genetic studies was partially funded by Research Into Ageing. The materials, anonymized data, and associated protocols are available on request for the SNPs and haplotypes presented in this article. Several of the coauthors (J.T.S., P.U., J.-M.A., M.P., J.K., B.T., and C.D.) are inventors involved in one to four patent applications (U.S. application numbers 11/325,330, 60/798,706, 60/805,522, and 60/863,438) related to the findings of this study.