title: Genome-wide association study of coronary artery disease in the Japanese.
abstract: A new understanding of the genetic basis of coronary artery disease (CAD) has recently emerged from genome-wide association (GWA) studies of common single-nucleotide polymorphisms (SNPs), thus far performed mostly in European-descent populations. To identify novel susceptibility gene variants for CAD and confirm those previously identified mostly in populations of European descent, a multistage GWA study was performed in the Japanese. In the discovery phase, we first genotyped 806 cases and 1337 controls with 451 382 SNP markers and subsequently assessed 34 selected SNPs with direct genotyping (541 additional cases) and in silico comparison (964 healthy controls). In the replication phase, involving 3052 cases and 6335 controls, 12 SNPs were tested; CAD association was replicated and/or verified for 4 (of 12) SNPs from 3 loci: near BRAP and ALDH2 on 12q24 (P=1.6 × 10(-34)), HLA-DQB1 on 6p21 (P=4.7 × 10(-7)), and CDKN2A/B on 9p21 (P=6.1 × 10(-16)). On 12q24, we identified the strongest association signal with the strength of association substantially pronounced for a subgroup of myocardial infarction cases (P=1.4 × 10(-40)). On 6p21, an HLA allele, DQB1(*)0604, could show one of the most prominent association signals in an ∼8-Mb interval that encompasses the LTA gene, where an association with myocardial infarction had been reported in another Japanese study. CAD association was also identified at CDKN2A/B, as previously reported in different populations of European descent and Asians. Thus, three loci confirmed in the Japanese GWA study highlight the likely presence of risk alleles with two types of genetic effects - population specific and common - on susceptibility to CAD.
authors.affiliation: Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Takeuchi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokota
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Eitaro
authors.initials: E
authors.lastname: Nakashima
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Asano
authors.forename: Masato
authors.initials: M
authors.lastname: Isono
authors.forename: Toru
authors.initials: T
authors.lastname: Nabika
authors.forename: Takao
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Akihiro
authors.initials: A
authors.lastname: Fujioka
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Awata
authors.forename: Keizo
authors.initials: K
authors.lastname: Ohnaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakatochi
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kitajima
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.forename: Jiro
authors.initials: J
authors.lastname: Nakamura
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imai
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimamoto
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yamori
authors.forename: Shuhei
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Shotai
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kato
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results