An expanded genome-wide association study of Type 2 diabetes in Europeans

2.50
Hdl Handle:
http://hdl.handle.net/11287/620388
Title:
An expanded genome-wide association study of Type 2 diabetes in Europeans
Authors:
Scott, R. A. [et al]; Hattersley, Andrew T.
Abstract:
To characterise type 2 diabetes (T2D) associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D cases and 132,532 controls of European ancestry after imputation using the 1000 Genomes multi-ethnic reference panel. Promising association signals were followed-up in additional data sets (of 14,545 or 7,397 T2D cases and 38,994 or 71,604 controls). We identified 13 novel T2D-associated loci (p<5×10-8), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common SNVs. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion, and in adipocytes, monocytes and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology
Citation:
An expanded genome-wide association study of Type 2 diabetes in Europeans. 2017 May 31. Diabetes
Publisher:
American Diabetes Association
Journal:
Diabetes
Issue Date:
31-May-2017
URI:
http://hdl.handle.net/11287/620388
DOI:
10.2337/db16-1253
PubMed ID:
28566273
Additional Links:
http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=28566273
Type:
Journal Article
Language:
en
Appears in Collections:
Diabetes/Endocrine Services; 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorScott, R. A. [et al]en
dc.contributor.authorHattersley, Andrew T.en
dc.date.accessioned2017-09-08T09:27:26Z-
dc.date.available2017-09-08T09:27:26Z-
dc.date.issued2017-05-31-
dc.identifier.citationAn expanded genome-wide association study of Type 2 diabetes in Europeans. 2017 May 31. Diabetesen
dc.identifier.pmid28566273-
dc.identifier.doi10.2337/db16-1253-
dc.identifier.urihttp://hdl.handle.net/11287/620388-
dc.description.abstractTo characterise type 2 diabetes (T2D) associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D cases and 132,532 controls of European ancestry after imputation using the 1000 Genomes multi-ethnic reference panel. Promising association signals were followed-up in additional data sets (of 14,545 or 7,397 T2D cases and 38,994 or 71,604 controls). We identified 13 novel T2D-associated loci (p<5×10-8), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common SNVs. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion, and in adipocytes, monocytes and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiologyen
dc.language.isoenen
dc.publisherAmerican Diabetes Associationen
dc.relation.urlhttp://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=28566273en
dc.rightsArchived with thanks to Diabetesen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen
dc.titleAn expanded genome-wide association study of Type 2 diabetes in Europeansen
dc.typeJournal Articleen
dc.identifier.journalDiabetesen
dc.type.versionIn press (epub ahead of print)en

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