Association of Transcription Factor 7-Like 2 ( TCF7L2 ) Variants With Type 2 Diabetes in a Finnish Sample
Laura J. Scott 1 ,
Lori L. Bonnycastle 2 ,
Cristen J. Willer 1 ,
Andrew G. Sprau 2 ,
Anne U. Jackson 1 ,
Narisu Narisu 2 ,
William L. Duren 1 ,
Peter S. Chines 2 ,
Heather M. Stringham 1 ,
Michael R. Erdos 2 ,
Timo T. Valle 3 ,
Jaakko Tuomilehto 3 4 5 ,
Richard N. Bergman 6 ,
Karen L. Mohlke 7 ,
Francis S. Collins 2 and
Michael Boehnke 1
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
Abstract
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.
FUSION, Finland-United States Investigation of NIDDM Genetics
GIST, Genotype-IBD Sharing Test
LD, linkage disequilibrium
NGT, normal glucose tolerance
SNP, single nucleotide polymorphism
Footnotes
Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted June 15, 2006.
Received March 14, 2006.
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Association of Transcription Factor 7-Like 2 (TCF7L2) Variants With Type 2 Diabetes in a Finnish Sample

10.2337/db06-0341