Type 2 diabetes whole-genome association study in four populations: The DiaGen consortium

Jukka T. Salonen, Pekka Uimari, Juha Matti Aalto, Mia Pirskanen, Jari Kaikkonen, Boryana Todorova, Jelena Hyppönen, Veli Pekka Korhonen, Janne Asikainen, Christopher Devine, Tomi Pekka Tuomainen, Jan Luedemann, Matthias Nauck, Wolfgang Kerner, Richard H. Stephens, John P. New, William E. Ollier, J. Martin Gibson, Antony Payton, Michael A. HoranNeil Pendleton, Walt Mahoney, David Meyre, Jerôme Delplanque, Philippe Froguel, Oren Luzzatto, Benjamin Yakir, Ariel Darvasi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

161 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)338-345
Number of pages8
JournalAmerican Journal of Human Genetics
Volume81
Issue number2
DOIs
StatePublished - Aug 2007

Bibliographical note

Funding 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.

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