title: Genomewide association analysis of coronary artery disease.
abstract: BACKGROUND
  Modern genotyping platforms permit a systematic search for inherited components of complex diseases. We performed a joint analysis of two genomewide association studies of coronary artery disease.
  
  
  METHODS
  We first identified chromosomal loci that were strongly associated with coronary artery disease in the Wellcome Trust Case Control Consortium (WTCCC) study (which involved 1926 case subjects with coronary artery disease and 2938 controls) and looked for replication in the German MI [Myocardial Infarction] Family Study (which involved 875 case subjects with myocardial infarction and 1644 controls). Data on other single-nucleotide polymorphisms (SNPs) that were significantly associated with coronary artery disease in either study (P<0.001) were then combined to identify additional loci with a high probability of true association. Genotyping in both studies was performed with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix).
  
  
  RESULTS
  Of thousands of chromosomal loci studied, the same locus had the strongest association with coronary artery disease in both the WTCCC and the German studies: chromosome 9p21.3 (SNP, rs1333049) (P=1.80x10(-14) and P=3.40x10(-6), respectively). Overall, the WTCCC study revealed nine loci that were strongly associated with coronary artery disease (P<1.2x10(-5) and less than a 50% chance of being falsely positive). In addition to chromosome 9p21.3, two of these loci were successfully replicated (adjusted P<0.05) in the German study: chromosome 6q25.1 (rs6922269) and chromosome 2q36.3 (rs2943634). The combined analysis of the two studies identified four additional loci significantly associated with coronary artery disease (P<1.3x10(-6)) and a high probability (>80%) of a true association: chromosomes 1p13.3 (rs599839), 1q41 (rs17465637), 10q11.21 (rs501120), and 15q22.33 (rs17228212).
  
  
  CONCLUSIONS
  We identified several genetic loci that, individually and in aggregate, substantially affect the risk of development of coronary artery disease.
authors.affiliation: University of Leicester, Leicester, United Kingdom. njs@le.ac.uk
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Alistair S
authors.initials: AS
authors.lastname: Hall
authors.forename: Christian
authors.initials: C
authors.lastname: Hengstenberg
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.forename: Bjoern
authors.initials: B
authors.lastname: Mayer
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Dixon
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Peter
authors.initials: P
authors.lastname: Braund
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Barrett
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Stevens
authors.forename: Silke
authors.initials: S
authors.lastname: Szymczak
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Tregouet
authors.forename: Mark M
authors.initials: MM
authors.lastname: Iles
authors.forename: Friedrich
authors.initials: F
authors.lastname: Pahlke
authors.forename: Helen
authors.initials: H
authors.lastname: Pollard
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.forename: Francois
authors.initials: F
authors.lastname: Cambien
authors.forename: Marcus
authors.initials: M
authors.lastname: Fischer
authors.forename: Willem
authors.initials: W
authors.lastname: Ouwehand
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Balmforth
authors.forename: Andrea
authors.initials: A
authors.lastname: Baessler
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ball
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
authors.forename: Ingrid
authors.initials: I
authors.lastname: Braenne
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Martin D
authors.initials: MD
authors.lastname: Tobin
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: John R
authors.initials: JR
authors.lastname: Thompson
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
mesh_terms: D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D005819:Genetic Markers