Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Paul Franks

Paul Franks

Principal investigator

Paul Franks

An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans

Author

  • Robert A. Scott
  • Laura J Scott
  • Reedik Mägi
  • Letizia Marullo
  • Kyle J Gaulton
  • Marika Kaakinen
  • Peter Almgren
  • Valeriya Lyssenko
  • Leif Groop
  • Paul Franks

Summary, in English

To characterize 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 case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). 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 single nucleotide variants. 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. © 2017 by the American Diabetes Association.

Department/s

  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Hypertension
  • Genomics, Diabetes and Endocrinology
  • Genetic and Molecular Epidemiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2017

Language

English

Pages

2888-2902

Publication/Series

Diabetes

Volume

66

Issue

11

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes
  • Medical Genetics

Keywords

  • Caucasian
  • gene expression regulation
  • genetic variation
  • genetics
  • genome-wide association study
  • human
  • non insulin dependent diabetes mellitus
  • physiology
  • Diabetes Mellitus, Type 2
  • European Continental Ancestry Group
  • Gene Expression Regulation
  • Genetic Variation
  • Genome-Wide Association Study
  • Humans

Status

Published

Research group

  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Hypertension
  • Genomics, Diabetes and Endocrinology
  • Genetic and Molecular Epidemiology

ISBN/ISSN/Other

  • ISSN: 1939-327X