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Olle Melander

Principal investigator

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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author

  • Nora Franceschini
  • Bo Hedblad
  • Cristiano Fava
  • Olle Melander
  • Arne Lindgren
  • Johan L M Björkegren
  • Christopher J. O’Donnell

Summary, in English

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Department/s

  • Cardiovascular Research - Epidemiology
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Hypertension
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Clinical Stroke Research Group

Publishing year

2018

Language

English

Publication/Series

Nature Communications

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cardiovascular Research - Epidemiology
  • Cardiovascular Research - Hypertension
  • Clinical Stroke Research Group

ISBN/ISSN/Other

  • ISSN: 2041-1723