Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field We recently described an association between risk of type 2diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR)...

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Published in:Nature Genetics
Main Authors: Helgason, Agnar, Palsson, Snaebjorn, Thorleifsson, Gudmar, Grant, Struan F A, Emilsson, Valur, Gunnarsdottir, Steinunn, Adeyemo, Adebowale, Chen, Yuanxiu, Chen, Guanjie, Reynisdottir, Inga, Benediktsson, Rafn, Hinney, Anke, Hansen, Torben, Andersen, Gitte, Borch-Johnsen, Knut, Jorgensen, Torben, Schäfer, Helmut, Faruque, Mezbah, Doumatey, Ayo, Zhou, Jie, Wilensky, Robert L, Reilly, Muredach P, Rader, Daniel J, Bagger, Yu, Christiansen, Claus, Sigurdsson, Gunnar, Hebebrand, Johannes, Pedersen, Oluf, Thorsteinsdottir, Unnur, Gulcher, Jeffrey R, Kong, Augustine, Rotimi, Charles, Stefansson, Kari
Format: Article in Journal/Newspaper
Language:English
Published: Nature Pub. Co. 2007
Subjects:
African Continental Ancestry Group
Iceland
Body Mass Index
Case-Control Studies
Diabetes Mellitus
Type 2
Genetic Predisposition to Disease
Polymorphism
Single Nucleotide
TCF Transcription Factors
Online Access:http://hdl.handle.net/2336/13070
https://doi.org/10.1038/ng1960
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Summary:To access publisher full text version of this article. Please click on the hyperlink in Additional Links field We recently described an association between risk of type 2diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR) of 17%-28% in three populations of European ancestry. Here, we refine the definition of the TCF7L2 type 2diabetes risk variant, HapB(T2D), to the ancestral T allele of a SNP, rs7903146, through replication in West African and Danish type 2 diabetes case-control studies and an expanded Icelandic study. We also identify another variant of the same gene, HapA, that shows evidence of positive selection in East Asian, European and West African populations. Notably, HapA shows a suggestive association with body mass index and altered concentrations of the hunger-satiety hormones ghrelin and leptin in males, indicating that the selective advantage of HapA may have been mediated through effects on energy metabolism.

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