title: Genetically determined height and coronary artery disease.
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<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 quartile 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. (Funded by the British Heart Foundation and others.).
authors: The authors' affiliations are listed in the Appendix.
authors: Christopher P
authors: CP
authors: Nelson
authors: Stephen E
authors: SE
authors: Hamby
authors: Danish
authors: D
authors: Saleheen
authors: Jenna C
authors: JC
authors: Hopewell
authors: Lingyao
authors: L
authors: Zeng
authors: Themistocles L
authors: TL
authors: Assimes
authors: Stavroula
authors: S
authors: Kanoni
authors: Christina
authors: C
authors: Willenborg
authors: Stephen
authors: S
authors: Burgess
authors: Phillipe
authors: P
authors: Amouyel
authors: Sonia
authors: S
authors: Anand
authors: Stefan
authors: S
authors: Blankenberg
authors: Bernhard O
authors: BO
authors: Boehm
authors: Robert J
authors: RJ
authors: Clarke
authors: Rory
authors: R
authors: Collins
authors: George
authors: G
authors: Dedoussis
authors: Martin
authors: M
authors: Farrall
authors: Paul W
authors: PW
authors: Franks
authors: Leif
authors: L
authors: Groop
authors: Alistair S
authors: AS
authors: Hall
authors: Anders
authors: A
authors: Hamsten
authors: Christian
authors: C
authors: Hengstenberg
authors: G Kees
authors: GK
authors: Hovingh
authors: Erik
authors: E
authors: Ingelsson
authors: Sekar
authors: S
authors: Kathiresan
authors: Frank
authors: F
authors: Kee
authors: Inke R
authors: IR
authors: König
authors: Jaspal
authors: J
authors: Kooner
authors: Terho
authors: T
authors: Lehtimäki
authors: Winifred
authors: W
authors: März
authors: Ruth
authors: R
authors: McPherson
authors: Andres
authors: A
authors: Metspalu
authors: Markku S
authors: MS
authors: Nieminen
authors: Christopher J
authors: CJ
authors: O'Donnell
authors: Colin N A
authors: CN
authors: Palmer
authors: Annette
authors: A
authors: Peters
authors: Markus
authors: M
authors: Perola
authors: Muredach P
authors: MP
authors: Reilly
authors: Samuli
authors: S
authors: Ripatti
authors: Robert
authors: R
authors: Roberts
authors: Veikko
authors: V
authors: Salomaa
authors: Svati H
authors: SH
authors: Shah
authors: Stefan
authors: S
authors: Schreiber
authors: Agneta
authors: A
authors: Siegbahn
authors: Unnur
authors: U
authors: Thorsteinsdottir
authors: Giovani
authors: G
authors: Veronesi
authors: Nicholas
authors: N
authors: Wareham
authors: Cristen J
authors: CJ
authors: Willer
authors: Pierre A
authors: PA
authors: Zalloua
authors: Jeanette
authors: J
authors: Erdmann
authors: Panos
authors: P
authors: Deloukas
authors: Hugh
authors: H
authors: Watkins
authors: Heribert
authors: H
authors: Schunkert
authors: John
authors: J
authors: Danesh
authors: John R
authors: JR
authors: Thompson
authors: Nilesh J
authors: NJ
authors: Samani
mesh_terms: D000328:Adult; D001827:Body Height / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000209:etiology / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications; D016017:Odds Ratio; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D008078:Cholesterol, LDL; D014280:Triglycerides