Research Papers:
Identification of polymorphisms in 12q24.1, ACAD10, and BRAP as novel genetic determinants of blood pressure in Japanese by exome-wide association studies
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 1724 views | HTML 2348 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: hypertension, blood pressure, genetics, exome-wide association study, polymorphism
Received: March 19, 2017 Accepted: April 05, 2017 Published: April 27, 2017
ABSTRACT
We performed exome-wide association studies to identify genetic variants that influence systolic or diastolic blood pressure or confer susceptibility to hypertension in Japanese. The exome-wide association studies were performed with the use of Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays and with 14,678 subjects, including 8215 individuals with hypertension and 6463 controls. The relation of genotypes of 41,843 single nucleotide polymorphisms to systolic or diastolic blood pressure was examined by linear regression analysis. After Bonferroni’s correction, 44 and eight polymorphisms were significantly (P < 1.19 × 10–6) associated with systolic or diastolic blood pressure, respectively, with six polymorphisms (rs12229654, rs671, rs11066015, rs2074356, rs3782886, rs11066280) being associated with both systolic and diastolic blood pressure. Examination of the relation of allele frequencies to hypertension with Fisher’s exact test revealed that 100 of the 41,843 single nucleotide polymorphisms were significantly (P < 1.19 × 10–6) associated with hypertension. Subsequent multivariable logistic regression analysis with adjustment for age and sex showed that five polymorphisms (rs150854849, rs202069030, rs139012426, rs12229654, rs76974938) were significantly (P < 1.25 × 10–4) associated with hypertension. The polymorphism rs12229654 was thus associated with both systolic and diastolic blood pressure and with hypertension. Six polymorphisms (rs12229654 at 12q24.1, rs671 of ALDH2, rs11066015 of ACAD10, rs2074356 and rs11066280 of HECTD4, and rs3782886 of BRAP) were found to be associated with both systolic and diastolic blood pressure, with those at 12q24.1 or in ACAD10 or BRAP being novel determinants of blood pressure in Japanese.
![Creative Commons License](/images/80x15.png)
PII: 17474