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

Genetically Determined Height and Coronary Artery Disease

Author

  • C. P. Nelson
  • S. E. Hamby
  • D. Saleheen
  • J. C. Hopewell
  • L. Zeng
  • T. L. Assimes
  • S. Kanoni
  • C. Willenborg
  • S. Burgess
  • P. Amouyel
  • S. Anand
  • S. Blankenberg
  • B. O. Boehm
  • R. J. Clarke
  • R. Collins
  • G. Dedoussis
  • M. Farrall
  • Paul Franks
  • Leif Groop
  • A. S. Hall
  • A. Hamsten
  • C. Hengstenberg
  • G. Kees Hovingh
  • E. Ingelsson
  • S. Kathiresan
  • F. Kee
  • I. R. Koenig
  • J. Kooner
  • T. Lehtimaeki
  • W. Maerz
  • R. McPherson
  • A. Metspalu
  • M. S. Nieminen
  • C. J. O'Donnell
  • C. N. A. Palmer
  • A. Peters
  • M. Perola
  • M. P. Reilly
  • S. Ripatti
  • R. Roberts
  • V. Salomaa
  • S. H. Shah
  • S. Schreiber
  • A. Siegbahn
  • U. Thorsteinsdottir
  • G. Veronesi
  • N. Wareham
  • C. J. Willer
  • P. A. Zalloua
  • J. Erdmann
  • P. Deloukas
  • H. Watkins
  • H. Schunkert
  • J. Danesh
  • J. R. Thompson
  • N. J. Samani

Summary, in English

BACKGROUND The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. METHODS We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. RESULTS We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quar-tile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. CONCLUSIONS There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association.

Department/s

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

Publishing year

2015

Language

English

Pages

1608-1618

Publication/Series

New England Journal of Medicine

Volume

372

Issue

17

Document type

Journal article

Publisher

Massachusetts Medical Society

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Genetic and Molecular Epidemiology

ISBN/ISSN/Other

  • ISSN: 0028-4793