KMID : 0620920170490120005
|
|
Experimental & Molecular Medicine 2017 Volume.49 No. 12 p.5 ~ p.5
|
|
Longitudinal exome-wide association study to identify genetic susceptibility loci for hypertension in a Japanese population
|
|
Yasukochi Yoshiki
Sakuma Jun Takeuchi Ichiro Kato Kimihiko Oguri Mitsutoshi Fujimaki Tetsuo Horibe Hideki Yamada Yoshiji
|
|
Abstract
|
|
|
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.
|
|
KEYWORD
|
|
Evolutionary biology, Genome-wide association studies
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|