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Genome-wide association studies of late-onset cardiovascular disease.

Smith, Gustav LU and Newton-Cheh, Christopher (2015) In Journal of Molecular and Cellular Cardiology 83(Apr 11). p.131-141
Abstract
Human genetics is a powerful tool for discovering causal mediators of human disease and physiology. Cardiovascular diseases with late onset in the lifecourse have historically not been considered genetic diseases, but in recent years the contribution of a heritable factor has been established. More importantly, over the last decade genome-wide association studies (GWASs) have identified many loci associated with late-onset cardiovascular diseases including coronary artery disease, carotid artery disease, ischemic stroke, aortic aneurysm, peripheral vascular disease, atrial fibrillation, valvular disease and correlates of vascular and myocardial function. Here we review findings from GWASs considered statistically robust with regard to... (More)
Human genetics is a powerful tool for discovering causal mediators of human disease and physiology. Cardiovascular diseases with late onset in the lifecourse have historically not been considered genetic diseases, but in recent years the contribution of a heritable factor has been established. More importantly, over the last decade genome-wide association studies (GWASs) have identified many loci associated with late-onset cardiovascular diseases including coronary artery disease, carotid artery disease, ischemic stroke, aortic aneurysm, peripheral vascular disease, atrial fibrillation, valvular disease and correlates of vascular and myocardial function. Here we review findings from GWASs considered statistically robust with regard to multiple testing (p<5×10(-8)) for late-onset cardiovascular diseases and traits. Although for only a handful of the 92 genetic loci described here have the mechanisms underlying disease association been established, new and previously unsuspected pathways have been implicated for several conditions. Examples include a role for NO signaling in myocardial repolarization and sudden cardiac death and a role for the protein sortilin in lipid metabolism and coronary artery disease. Genetic loci with multiple trait associations have also provided novel biological insights. For example, of the 46 genetic loci associated with coronary artery disease, only 16 are also associated with conventional risk factors for cardiovascular disease whereas the remaining two thirds may reflect novel pathways. Much work remains to functionally characterize genetic loci and for clinical utility, but accruing insights into the biological basis of cardiovascular aging in human populations promise to point to novel therapeutic and preventive strategies. This article is part of a Special Issue entitled 'SI:CV Aging'. (Less)
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author
and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Molecular and Cellular Cardiology
volume
83
issue
Apr 11
pages
131 - 141
publisher
Elsevier
external identifiers
  • pmid:25870159
  • wos:000356839100014
  • scopus:84937968994
  • pmid:25870159
ISSN
1095-8584
DOI
10.1016/j.yjmcc.2015.04.004
language
English
LU publication?
yes
id
e5e49190-4e81-40df-9563-73b41190953b (old id 5341972)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25870159?dopt=Abstract
date added to LUP
2016-04-01 11:16:45
date last changed
2022-01-26 06:52:19
@article{e5e49190-4e81-40df-9563-73b41190953b,
  abstract     = {{Human genetics is a powerful tool for discovering causal mediators of human disease and physiology. Cardiovascular diseases with late onset in the lifecourse have historically not been considered genetic diseases, but in recent years the contribution of a heritable factor has been established. More importantly, over the last decade genome-wide association studies (GWASs) have identified many loci associated with late-onset cardiovascular diseases including coronary artery disease, carotid artery disease, ischemic stroke, aortic aneurysm, peripheral vascular disease, atrial fibrillation, valvular disease and correlates of vascular and myocardial function. Here we review findings from GWASs considered statistically robust with regard to multiple testing (p&lt;5×10(-8)) for late-onset cardiovascular diseases and traits. Although for only a handful of the 92 genetic loci described here have the mechanisms underlying disease association been established, new and previously unsuspected pathways have been implicated for several conditions. Examples include a role for NO signaling in myocardial repolarization and sudden cardiac death and a role for the protein sortilin in lipid metabolism and coronary artery disease. Genetic loci with multiple trait associations have also provided novel biological insights. For example, of the 46 genetic loci associated with coronary artery disease, only 16 are also associated with conventional risk factors for cardiovascular disease whereas the remaining two thirds may reflect novel pathways. Much work remains to functionally characterize genetic loci and for clinical utility, but accruing insights into the biological basis of cardiovascular aging in human populations promise to point to novel therapeutic and preventive strategies. This article is part of a Special Issue entitled 'SI:CV Aging'.}},
  author       = {{Smith, Gustav and Newton-Cheh, Christopher}},
  issn         = {{1095-8584}},
  language     = {{eng}},
  number       = {{Apr 11}},
  pages        = {{131--141}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Molecular and Cellular Cardiology}},
  title        = {{Genome-wide association studies of late-onset cardiovascular disease.}},
  url          = {{http://dx.doi.org/10.1016/j.yjmcc.2015.04.004}},
  doi          = {{10.1016/j.yjmcc.2015.04.004}},
  volume       = {{83}},
  year         = {{2015}},
}