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Research Papers:

Identification of rs7350481 at chromosome 11q23.3 as a novel susceptibility locus for metabolic syndrome in Japanese individuals by an exome-wide association study

Yoshiji Yamada _, Jun Sakuma, Ichiro Takeuchi, Yoshiki Yasukochi, Kimihiko Kato, Mitsutoshi Oguri, Tetsuo Fujimaki, Hideki Horibe, Masaaki Muramatsu, Motoji Sawabe, Yoshinori Fujiwara, Yu Taniguchi, Shuichi Obuchi, Hisashi Kawai, Shoji Shinkai, Seijiro Mori, Tomio Arai and Masashi Tanaka

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Oncotarget. 2017; 8:39296-39308. https://doi.org/10.18632/oncotarget.16945

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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: yamada@gene.mie-u.ac.jp

Keywords: body mass index, obesity, metabolic syndrome, genetics, exome-wide association study

Received: February 15, 2017    Accepted: March 14, 2017    Published: April 07, 2017

ABSTRACT

We have performed exome-wide association studies to identify genetic variants that influence body mass index or confer susceptibility to obesity or metabolic syndrome in Japanese. The exome-wide association study for body mass index included 12,890 subjects, and those for obesity and metabolic syndrome included 12,968 subjects (3954 individuals with obesity, 9014 controls) and 6817 subjects (3998 individuals with MetS, 2819 controls), respectively. Exome-wide association studies were performed with Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The relation of genotypes of single nucleotide polymorphisms to body mass index was examined by linear regression analysis, and that of allele frequencies of single nucleotide polymorphisms to obesity or metabolic syndrome was evaluated with Fisher’s exact test. The exome-wide association studies identified six, 11, and 40 single nucleotide polymorphisms as being significantly associated with body mass index, obesity (P <1.21 × 10–6), or metabolic syndrome (P <1.20 × 10–6), respectively. Subsequent multivariable logistic regression analysis with adjustment for age and sex revealed that three and five single nucleotide polymorphisms were related (P < 0.05) to obesity or metabolic syndrome, respectively, with one of these latter polymorphisms—rs7350481 (C/T) at chromosome 11q23.3—also being significantly (P < 3.13 × 10–4) associated with metabolic syndrome. The polymorphism rs7350481 may thus be a novel susceptibility locus for metabolic syndrome in Japanese. In addition, single nucleotide polymorphisms in three genes (CROT, TSC1, RIN3) and at four loci (ANKK1, ZNF804B, CSRNP3, 17p11.2) were implicated as candidate determinants of obesity and metabolic syndrome, respectively.


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