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Replication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes

Authors: Zeggini, Eleftheria; Weedon, Michael N.; Lindgren, Cecilia M.; Frayling, Timothy M.; Elliott, Katherine S.; Lango, Hana; Timpson, Nicholas J.; +31 Authors

Replication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes

Abstract

The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1 , CDKN2A/CDKN2B , and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8 . Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes.

Keywords

Adult, Male, 571, 610, 270207 Quantitative Genetics, p16, Polymorphism, Single Nucleotide, C1, Meta-Analysis as Topic, Diabetes Mellitus, Humans, Genetic Predisposition to Disease, Polymorphism, Aged, Oligonucleotide Array Sequence Analysis, Homeodomain Proteins, Multidisciplinary, Genome, Genome, Human, 780105 Biological sciences, Genes, p16, Great Britain, Chromosome Mapping, Single Nucleotide, Middle Aged, Introns, United Kingdom, Insulin-Like Growth Factor Binding Proteins, Genes, Diabetes Mellitus, Type 2, Case-Control Studies, Female, Type 2, Human, Transcription Factors

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
2K
Top 0.1%
Top 0.1%
Top 0.01%
Green
bronze