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Olle Melander

Principal investigator

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Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease

Author

  • Wei Zhao
  • Asif Rasheed
  • Emmi Tikkanen
  • Jung-Jin Lee
  • Adam S. Butterworth
  • Joanna M. M. Howson
  • Marju Orho-Melander
  • Olle Melander

Summary, in English

To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLADRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D- CHD analysis identified eight variants-two of which are coding-where T2D and CHD associations appear to colocalize, including a new joint T2D-CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein. © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.

Department/s

  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Hypertension
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2017

Language

English

Pages

1450-1457

Publication/Series

Nature Genetics

Volume

49

Issue

10

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics

Keywords

  • fatty acid binding protein 4
  • icosapentaenoic acid ethyl ester
  • biological marker
  • HLA DRB5 antigen
  • Article
  • CCDC92 gene
  • controlled study
  • East Asian
  • European
  • gene
  • gene locus
  • genetic risk
  • genetic susceptibility
  • genetic variability
  • genetic variation
  • genome-wide association study
  • HLA DRB5 gene
  • human
  • ischemic heart disease
  • major clinical study
  • non insulin dependent diabetes mellitus
  • priority journal
  • single nucleotide polymorphism
  • South Asian
  • Asia
  • Asian continental ancestry group
  • Caucasian
  • comorbidity
  • comparative study
  • Coronary Disease
  • Diabetes Mellitus, Type 2
  • Europe
  • genetic predisposition
  • genetics
  • metabolic syndrome X
  • metabolism
  • missense mutation
  • molecularly targeted therapy
  • risk factor
  • Asian Continental Ancestry Group
  • Biomarkers
  • Comorbidity
  • European Continental Ancestry Group
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • HLA-DRB5 Chains
  • Humans
  • Metabolic Networks and Pathways
  • Metabolic Syndrome X
  • Molecular Targeted Therapy
  • Mutation, Missense
  • Polymorphism, Single Nucleotide
  • Risk Factors

Status

Published

Research group

  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 1546-1718