Research Papers:
Identification of STXBP2 as a novel susceptibility locus for myocardial infarction in Japanese individuals by an exome-wide association study
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 1515 views | HTML 2713 views | ?
Abstract
Yoshiji Yamada1,2, Jun Sakuma2,3,4, Ichiro Takeuchi2,4,5, Yoshiki Yasukochi1,2, Kimihiko Kato1,6, Mitsutoshi Oguri1,7, Tetsuo Fujimaki8, Hideki Horibe9, Masaaki Muramatsu10, Motoji Sawabe11, Yoshinori Fujiwara12, Yu Taniguchi12, Shuichi Obuchi13, Hisashi Kawai13, Shoji Shinkai14, Seijiro Mori15, Tomio Arai16 and Masashi Tanaka17
1Department of Human Functional Genomics, Advanced Science Research Promotion Center, Mie University, Tsu, Japan
2CREST, Japan Science and Technology Agency, Kawaguchi, Japan
3Computer Science Department, College of Information Science, University of Tsukuba, Tsukuba, Japan
4RIKEN Center for Advanced Intelligence Project, Tokyo, Japan
5Department of Computer Science, Nagoya Institute of Technology, Nagoya, Japan
6Department of Internal Medicine, Meitoh Hospital, Nagoya, Japan
7Department of Cardiology, Kasugai Municipal Hospital, Kasugai, Japan
8Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Japan
9Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan
10Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
11Section of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan
12Research Team for Social Participation and Community Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
13Research Team for Promoting Support System for Home Care, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
14Research Team for Social Participation and Health Promotion, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
15Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
16Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
17Department of Clinical Laboratory, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
Correspondence to:
Yoshiji Yamada, email: [email protected]
Keywords: myocardial infarction, coronary artery disease, genetics, polymorphism, exome-wide association study
Received: January 27, 2017 Accepted: March 02, 2017 Published: March 23, 2017
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 16536