title: Identification of STXBP2 as a novel susceptibility locus for myocardial infarction in Japanese individuals by an exome-wide association study.
abstract: We performed exome-wide association studies to identify genetic variants-in particular, low-frequency variants with a large effect size-that confer susceptibility to coronary artery disease or myocardial infarction in Japanese. The exome-wide association studies were performed with 12,698 individuals (3488 subjects with coronary artery disease including 2438 with myocardial infarction, 9210 controls) and with the use of the Illumina HumanExome-12 DNA Analysis or Infinium Exome-24 BeadChip. The relation of allele frequencies for 41,339 single nucleotide polymorphisms that passed quality control to coronary artery disease or myocardial infarction was examined with Fisher's exact test. The exome-wide association study for coronary artery disease revealed that 126 single nucleotide polymorphisms were significantly (P <1.21 × 10-6) associated with this condition. Multivariable logistic regression analysis with adjustment for age, sex, and the prevalence of hypertension, diabetes mellitus, and dyslipidemia showed that six of these polymorphisms were related (P < 0.01) to coronary artery disease, but none was significantly (P < 9.92 × 10-5) associated with this condition. The exome-wide association study for myocardial infarction revealed that 114 single nucleotide polymorphisms were significantly (P <1.21 × 10-6) associated with this condition. Multivariable logistic regression analysis with adjustment for covariates revealed that nine of these polymorphisms were related (P < 0.01) to myocardial infarction. Among these nine polymorphisms, rs188212047 [G/T (L212F)] of STXBP2 was significantly (dominant model; P = 4.84 × 10-8; odds ratio, 2.94) associated with myocardial infarction. STXBP2 may thus be a novel susceptibility locus for myocardial infarction in Japanese.
authors.affiliation: Department of Human Functional Genomics, Advanced Science Research Promotion Center, Mie University, Tsu, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan.
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: CREST, Japan Science and Technology Agency, Kawaguchi, Japan.|Computer Science Department, College of Information Science, University of Tsukuba, Tsukuba, Japan.|RIKEN Center for Advanced Intelligence Project, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Sakuma
authors.affiliation: CREST, Japan Science and Technology Agency, Kawaguchi, Japan.|RIKEN Center for Advanced Intelligence Project, Tokyo, Japan.|Department of Computer Science, Nagoya Institute of Technology, Nagoya, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takeuchi
authors.affiliation: Department of Human Functional Genomics, Advanced Science Research Promotion Center, Mie University, Tsu, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yasukochi
authors.affiliation: Department of Human Functional Genomics, Advanced Science Research Promotion Center, Mie University, Tsu, Japan.|Department of Internal Medicine, Meitoh Hospital, Nagoya, Japan.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Human Functional Genomics, Advanced Science Research Promotion Center, Mie University, Tsu, Japan.|Department of Cardiology, Kasugai Municipal Hospital, Kasugai, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Oguri
authors.affiliation: Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujimaki
authors.affiliation: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Horibe
authors.affiliation: Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Muramatsu
authors.affiliation: Section of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Motoji
authors.initials: M
authors.lastname: Sawabe
authors.affiliation: Research Team for Social Participation and Community Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Research Team for Social Participation and Community Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Taniguchi
authors.affiliation: Research Team for Promoting Support System for Home Care, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Obuchi
authors.affiliation: Research Team for Promoting Support System for Home Care, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kawai
authors.affiliation: Research Team for Social Participation and Health Promotion, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Shinkai
authors.affiliation: Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
authors.forename: Seijiro
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.affiliation: Department of Clinical Laboratory, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D051938:Munc18 Proteins / Q000235:genetics*; D009203:Myocardial Infarction / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D000073359:Exome Sequencing
chemical_list: D051938:Munc18 Proteins; C497940:STXBP2 protein, human
keywords: coronary artery disease; exome-wide association study; genetics; myocardial infarction; polymorphism