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Genetically Determined Height and Coronary Artery Disease

Nelson, C. P. ; Hamby, S. E. ; Saleheen, D. ; Hopewell, J. C. ; Zeng, L. ; Assimes, T. L. ; Kanoni, S. ; Willenborg, C. ; Burgess, S. and Amouyel, P. , et al. (2015) In New England Journal of Medicine 372(17). p.1608-1618
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
New England Journal of Medicine
volume
372
issue
17
pages
1608 - 1618
publisher
Massachusetts Medical Society
external identifiers
  • wos:000353294000006
  • scopus:84928021248
  • pmid:25853659
ISSN
0028-4793
DOI
10.1056/NEJMoa1404881
language
English
LU publication?
yes
id
f8d8f810-f1a7-4c10-af77-a0b7e693ee90 (old id 5386538)
date added to LUP
2016-04-01 10:35:10
date last changed
2024-04-07 12:57:18
@article{f8d8f810-f1a7-4c10-af77-a0b7e693ee90,
  abstract     = {{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&lt;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&lt;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.}},
  author       = {{Nelson, C. P. and Hamby, S. E. and Saleheen, D. and Hopewell, J. C. and Zeng, L. and Assimes, T. L. and Kanoni, S. and Willenborg, C. and Burgess, S. and Amouyel, P. and Anand, S. and Blankenberg, S. and Boehm, B. O. and Clarke, R. J. and Collins, R. and Dedoussis, G. and Farrall, M. and Franks, Paul and Groop, Leif and Hall, A. S. and Hamsten, A. and Hengstenberg, C. and Hovingh, G. Kees and Ingelsson, E. and Kathiresan, S. and Kee, F. and Koenig, I. R. and Kooner, J. and Lehtimaeki, T. and Maerz, W. and McPherson, R. and Metspalu, A. and Nieminen, M. S. and O'Donnell, C. J. and Palmer, C. N. A. and Peters, A. and Perola, M. and Reilly, M. P. and Ripatti, S. and Roberts, R. and Salomaa, V. and Shah, S. H. and Schreiber, S. and Siegbahn, A. and Thorsteinsdottir, U. and Veronesi, G. and Wareham, N. and Willer, C. J. and Zalloua, P. A. and Erdmann, J. and Deloukas, P. and Watkins, H. and Schunkert, H. and Danesh, J. and Thompson, J. R. and Samani, N. J.}},
  issn         = {{0028-4793}},
  language     = {{eng}},
  number       = {{17}},
  pages        = {{1608--1618}},
  publisher    = {{Massachusetts Medical Society}},
  series       = {{New England Journal of Medicine}},
  title        = {{Genetically Determined Height and Coronary Artery Disease}},
  url          = {{https://lup.lub.lu.se/search/files/1967375/8310665.pdf}},
  doi          = {{10.1056/NEJMoa1404881}},
  volume       = {{372}},
  year         = {{2015}},
}