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Olle Melander

Principal investigator

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Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease.

Author

  • Maria Sabater-Lleal
  • Anders Mälarstig
  • Lasse Folkersen
  • María Soler Artigas
  • Damiano Baldassarre
  • Maryam Kavousi
  • Peter Almgren
  • Fabrizio Veglia
  • Guy Brusselle
  • Albert Hofman
  • Gunnar Engström
  • Oscar H Franco
  • Olle Melander
  • Gabrielle Paulsson-Berne
  • Hugh Watkins
  • Per Eriksson
  • Steve E Humphries
  • Elena Tremoli
  • Ulf de Faire
  • Martin D Tobin
  • Anders Hamsten

Summary, in English

Chronic obstructive pulmonary disease (COPD) independently associates with an increased risk of coronary artery disease (CAD), but it has not been fully investigated whether this co-morbidity involves shared pathophysiological mechanisms. To identify potential common pathways across the two diseases, we tested all recently published single nucleotide polymorphisms (SNPs) associated with human lung function (spirometry) for association with carotid intima-media thickness (cIMT) in 3,378 subjects with multiple CAD risk factors, and for association with CAD in a case-control study of 5,775 CAD cases and 7,265 controls. SNPs rs2865531, located in the CFDP1 gene, and rs9978142, located in the KCNE2 gene, were significantly associated with CAD. In addition, SNP rs9978142 and SNP rs3995090 located in the HTR4 gene, were associated with average and maximal cIMT measures. Genetic risk scores combining the most robustly spirometry-associated SNPs from the literature were modestly associated with CAD, (odds ratio (OR) (95% confidence interval (CI95) = 1.06 (1.03, 1.09); P-value = 1.5×10-4, per allele). In conclusion, our study suggests that some genetic loci implicated in determining human lung function also influence cIMT and susceptibility to CAD. The present results should help elucidate the molecular underpinnings of the co-morbidity observed across COPD and CAD.

Department/s

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

Publishing year

2014

Language

English

Publication/Series

PLoS ONE

Volume

9

Issue

8

Document type

Journal article

Publisher

Public Library of Science

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Epidemiology
  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 1932-6203