TY - JOUR
T1 - Genetically Determined Height and Coronary Artery Disease
AU - AUTHOR GROUP
AU - Nelson, Christopher P.
AU - Hamby, Stephen E.
AU - Saleheen, Danish
AU - Hopewell, Jenna C.
AU - Zeng, Lingyao
AU - Assimes, Themistocles L.
AU - Kanoni, Stavroula
AU - Willenborg, Christina
AU - Burgess, Stephen
AU - Amouyel, Phillipe
AU - Anand, Sonia
AU - Blankenberg, Stefan
AU - Boehm, Bernhard O.
AU - Clarke, Robert J.
AU - Collins, Rory
AU - Dedoussis, George
AU - Farrall, Martin
AU - Franks, Paul W.
AU - Groop, Leif
AU - Hall, Alistair S.
AU - Hamsten, Anders
AU - Hengstenberg, Christian
AU - Hovingh, G. Kees
AU - Ingelsson, Erik
AU - Kathiresan, Sekar
AU - Kee, Frank
AU - König, Inke R.
AU - Kooner, Jaspal
AU - Lehtimäki, Terho
AU - März, Winifred
AU - McPherson, Ruth
AU - Metspalu, Andres
AU - Nieminen, Markku S.
AU - O'Donnell, Christopher J.
AU - Palmer, Colin N. A.
AU - Peters, Annette
AU - Perola, Markus
AU - Reilly, Muredach P.
AU - Ripatti, Samuli
AU - Roberts, Robert
AU - Salomaa, Veikko
AU - Shah, Svati H.
AU - Schreiber, Stefan
AU - Siegbahn, Agneta
AU - Thorsteinsdottir, Unnur
AU - Veronesi, Giovani
AU - Wareham, Nicholas
AU - Willer, Cristen J.
AU - Zalloua, Pierre A.
AU - Erdmann, Jeanette
PY - 2015
Y1 - 2015
N2 - 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
AB - 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
U2 - https://doi.org/10.1056/NEJMoa1404881
DO - https://doi.org/10.1056/NEJMoa1404881
M3 - Article
C2 - 25853659
SN - 0028-4793
VL - 372
SP - 1608
EP - 1618
JO - New England journal of medicine
JF - New England journal of medicine
IS - 17
ER -