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Genetically determined height and coronary artery disease.
N. Engl. J. Med. 372, 1608-1618 (2015)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Body-mass Index; Blood-pressure; Association; Risk; Loci; Atherosclerosis; Metaanalysis; Variants; Plaques; Lipids
Language
english
Publication Year
2015
HGF-reported in Year
2015
ISSN (print) / ISBN
0028-4793
e-ISSN
1533-4406
Quellenangaben
Volume: 372,
Issue: 17,
Pages: 1608-1618
Publisher
Massachusetts Medical Society (MMS)
Publishing Place
Waltham
Reviewing status
Peer reviewed
Institute(s)
Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
Institute of Genetic Epidemiology (IGE)
POF-Topic(s)
30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-504000-001
G-504000-006
G-504100-001
G-504000-006
G-504100-001
WOS ID
WOS:000353294000006
Erfassungsdatum
2015-05-16