Population-specific risk of type 2 diabetes conferred by HNF4A P2 promoter variants: a lesson for replication studies.

Diabetes
Inês BarrosoPanagiotis Deloukas

Abstract

Single nucleotide polymorphisms (SNPs) in the P2 promoter region of HNF4A were originally shown to be associated with predisposition for type 2 diabetes in Finnish, Ashkenazi, and, more recently, Scandinavian populations, but they generated conflicting results in additional populations. We aimed to investigate whether data from a large-scale mapping approach would replicate this association in novel Ashkenazi samples and in U.K. populations and whether these data would allow us to refine the association signal. Using a dense linkage disequilibrium map of 20q, we selected SNPs from a 10-Mb interval centered on HNF4A. In a staged approach, we first typed 4,608 SNPs in case-control populations from four U.K. populations and an Ashkenazi population (n = 2,516). In phase 2, a subset of 763 SNPs was genotyped in 2,513 additional samples from the same populations. Combined analysis of both phases demonstrated association between HNF4A P2 SNPs (rs1884613 and rs2144908) and type 2 diabetes in the Ashkenazim (n = 991; P < 1.6 x 10(-6)). Importantly, these associations are significant in a subset of Ashkenazi samples (n = 531) not previously tested for association with P2 SNPs (odds ratio [OR] approximately 1.7; P < 0.002), thus providing...Continue Reading

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Citations

Feb 15, 2011·Inflammatory Bowel Diseases·Alexandra I Thompson, Charlie W Lees
Sep 21, 2012·Current Diabetes Reports·Yoon Shin ChoChu Won Nho
Nov 17, 2009·Nature Genetics·UNKNOWN UK IBD Genetics ConsortiumDavid P Strachan
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Aug 13, 2011·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Suk-Kyun YangKyuyoung Song
May 1, 2009·Diabetes/metabolism Research and Reviews
Sep 24, 2015·Iranian Journal of Pediatrics·Hossein MoravejOmid Aryani
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Apr 25, 2009·Diabetes·Inga ProkopenkoUNKNOWN International Type 2 Diabetes 1q Consortium
Jul 1, 2009·Nature Reviews. Endocrinology·Elliot S Stolerman, Jose C Florez
Apr 2, 2016·Endocrine Reviews·Yisheng Yang, Lawrence Chan
Jan 20, 2016·Molecular Medicine Reports·Run MaWei Zhou

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Methods Mentioned

BETA
genotyping

Software Mentioned

SE
Stata

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