Longitudinal exome-wide association study to identify genetic susceptibility loci for hypertension in a Japanese population

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作者
Yoshiki Yasukochi
Jun Sakuma
Ichiro Takeuchi
Kimihiko Kato
Mitsutoshi Oguri
Tetsuo Fujimaki
Hideki Horibe
Yoshiji Yamada
机构
[1] Advanced Science Research Promotion Center,Department of Human Functional Genomics
[2] Mie University,Computer Science Department
[3] CREST,Department of Computer Science
[4] Japan Science and Technology Agency,Department of Internal Medicine
[5] College of Information Science,Department of Cardiology
[6] University of Tsukuba,Department of Cardiovascular Medicine
[7] RIKEN Center for Advanced Intelligence Project,Department of Cardiovascular Medicine
[8] Nagoya Institute of Technology,undefined
[9] Meitoh Hospital,undefined
[10] Kasugai Municipal Hospital,undefined
[11] Inabe General Hospital,undefined
[12] Gifu Prefectural Tajimi Hospital,undefined
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摘要
Genome-wide association studies have identified various genetic variants associated with complex disorders. However, these studies have commonly been conducted in a cross-sectional manner. Therefore, we performed a longitudinal exome-wide association study (EWAS) in a Japanese cohort. We aimed to identify genetic variants that confer susceptibility to hypertension using ~244 000 single-nucleotide variants (SNVs) and physiological data from 6026 Japanese individuals who underwent annual health check-ups for several years. After quality control, the association of hypertension with SNVs was tested using a generalized estimating equation model. Finally, our longitudinal EWAS detected seven hypertension-related SNVs that passed strict criteria. Among these variants, six SNVs were densely located at 12q24.1, and an East Asian-specific motif (haplotype) ‘CAAAA’ comprising five derived alleles was identified. Statistical analyses showed that the prevalence of hypertension in individuals with the East Asian-specific haplotype was significantly lower than that in individuals with the common haplotype ‘TGGGT’. Furthermore, individuals with the East Asian haplotype may be less susceptible to the adverse effects of smoking on hypertension. The longitudinal EWAS for the recessive model showed that a novel SNV, rs11917356 of COL6A5, was significantly associated with systolic blood pressure, and the derived allele at the SNV may have spread throughout East Asia in recent evolutionary time.
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页码:e409 / e409
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