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Association of Transcription Factor 7-Like 2 (TCF7L2) Variants With Type 2 Diabetes in a Finnish Sample

¹ Department of Biostatistics, School of Public Health, and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan
² Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland
³ Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland
⁴ Department of Public Health, University of Helsinki, Helsinki, Finland
⁵ South Ostrobothnia Central Hospital, Seinäjoki, Finland
⁶ Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
⁷ Department of Genetics, University of North Carolina, Chapel Hill, North Carolina

Address correspondence and reprint requests to Laura Scott, PhD, Department of Biostatistics, School of Public Health, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109-2029. E-mail: ljst{at}umich.edu

Abbreviations: FUSION, Finland-United States Investigation of NIDDM Genetics; GIST, Genotype-IBD Sharing Test; LD, linkage disequilibrium; NGT, normal glucose tolerance; SNP, single nucleotide polymorphism

Transcription factor 7-like 2 (TCF7L2) is part of the Wnt signaling pathway. Genetic variants within TCF7L2 on chromosome 10q were recently reported to be associated with type 2 diabetes in Icelandic, Danish, and American (U.S.) samples. We previously observed a modest logarithm of odds score of 0.61 on chromosome 10q, 1 Mb from TCF7L2, in the Finland-United States Investigation of NIDDM Genetics study. We tested the five associated TCF7L2 single nucleotide polymorphism (SNP) variants in a Finnish sample of 1,151 type 2 diabetic patients and 953 control subjects. We confirmed the association with the same risk allele (P value <0.05) for all five SNPs. Our strongest results were for rs12255372 (odds ratio [OR] 1.36 [95% CI 1.15–1.61], P = 0.00026) and rs7903146 (1.33 [1.14–1.56], P = 0.00042). Based on the CEU HapMap data, we selected and tested 12 additional SNPs to tag SNPs in linkage disequilibrium with rs12255372. None of these SNPs showed stronger evidence of association than rs12255372 or rs7903146 (OR 1.26, P 0.0054). Our results strengthen the evidence that one or more variants in TCF7L2 are associated with increased risk of type 2 diabetes.

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