ArticleDiabetes2008
Population-specific risk of type 2 diabetes conferred by HNF4A P2 promoter variants: a lesson for replication studies.
Article in Diabetes, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 3 of them syntheses that pooled it.
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Who cites it
21 citing papers in PubMed, 3 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Accounting for heterogeneity due to environmental sources in meta-analysis of genome-wide association studies.Communications biology · 2024Pooled it
- Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.Nature genetics · 2011Pooled it
- Random-effects model aimed at discovering associations in meta-analysis of genome-wide association studies.American journal of human genetics · 2011Pooled it
- Disentangling group specific QTL allele effects from genetic background epistasis using admixed individuals in GWAS: An application to maize flowering.PLoS genetics · 2020Article
- Association Analysis of the HNF4A Common Genetic Variants with Type 2 Diabetes Mellitus Risk.International journal of molecular and cellular medicine · 2019Article
- Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2 Diabetes.Endocrine reviews · 2016Review
- Oral Therapy in a Diabetic Patient With History of Infantile Hyperinsulinism.Iranian journal of pediatrics · 2015Article
- Hepatocyte nuclear factor 4 alpha polymorphisms and the metabolic syndrome in French-Canadian youth.PloS one · 2015Article
- Genome-wide association study identifies two novel Loci with sex-specific effects for type 2 diabetes mellitus and glycemic traits in a korean population.Diabetes & metabolism journal · 2014Article
- Genetics of type 2 diabetes in East Asian populations.Current diabetes reports · 2012Review
- Association between genetic variants in the HNF4A gene and childhood-onset Crohn's disease.Genes and immunity · 2012Article
- Interpreting meta-analyses of genome-wide association studies.PLoS genetics · 2012Article
- Examination of Rare Variants in HNF4 α in European Americans with Type 2 Diabetes.Journal of diabetes & metabolism · 2011Article
- Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Upregulation of Scavenger Receptor BI by Hepatic Nuclear Factor 4α through a Peroxisome Proliferator-Activated Receptor γ-Dependent Mechanism in Liver.PPAR research · 2011Article
- Gene-gene interactions lead to higher risk for development of type 2 diabetes in an Ashkenazi Jewish population.PloS one · 2010Article
- Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region.Nature genetics · 2009Article
- Genomics of type 2 diabetes mellitus: implications for the clinician.Nature reviews. Endocrinology · 2009Review
- Linkage disequilibrium mapping of the replicated type 2 diabetes linkage signal on chromosome 1q.Diabetes · 2009Article
- FitSNPs: highly differentially expressed genes are more likely to have variants associated with disease.Genome biology · 2008Article
Corrections and comments
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Authors and funding
22 authors at 10 institutions in 3 countries.
Funding
Abstract
objectiveSingle 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. RESEARCH DESIGN AND
methodsUsing 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.
resultsCombined 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 replication within the Ashkenazim. In the U.K. populations, this association was not significant (n = 4,022; P > 0.5), and the estimate for the OR was much smaller (OR 1.04; [95%CI 0.91-1.19]).
conclusionsThese data indicate that the risk conferred by HNF4A P2 is significantly different between U.K. and Ashkenazi populations (P < 0.00007), suggesting that the underlying causal variant remains unidentified. Interactions with other genetic or environmental factors may also contribute to this difference in risk between populations.
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