1. Population-specific and trans-ancestry genome-wide analyses identify distinct and shared genetic risk loci for coronary artery disease
- Author
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Naoyuki Takashima, Yasushi Sakata, Shoichiro Tsugane, Momoko Horikoshi, Yasuhiko Sakata, Hiroshi Akazawa, Yukihide Momozawa, Kaoru Ito, Hiroaki Ikezaki, Michiaki Kubo, Teruhide Koyama, Mariko Naito, Masato Akiyama, Satoshi Koyama, Kenji Wakai, Hiroyuki Morita, Hiroshi Sato, Atsushi Takahashi, Taiki Yamaji, Chikashi Terao, Seitaro Nomura, Jeong-Sun Seo, Hirotaka Ieki, Koichiro Higasa, Yoshihiro Onouchi, Kokichi Arisawa, Koichi Matsuda, Keitaro Tanaka, Fumihiko Matsuda, Yoichiro Kamatani, Shinichiro Suna, Norie Sawada, Yoshinori Murakami, Issei Komuro, Hiroshi Matsunaga, Changhoon Kim, Kiyonori Kuriki, Motoki Iwasaki, Kouichi Ozaki, Hiroyuki Aburatani, and Masatsugu Hori
- Subjects
Adult ,Genotype ,Genome-wide association study ,Coronary Artery Disease ,Biology ,Genome ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Risk Factors ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,Alleles ,Aged ,030304 developmental biology ,Genetic association ,0303 health sciences ,Haplotype ,Chromosome Mapping ,Genetic Pleiotropy ,Middle Aged ,medicine.disease ,Pedigree ,Meta-analysis ,Cholestanetriol 26-Monooxygenase ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
To elucidate the genetics of coronary artery disease (CAD) in the Japanese population, we conducted a large-scale genome-wide association study of 168,228 individuals of Japanese ancestry (25,892 cases and 142,336 controls) with genotype imputation using a newly developed reference panel of Japanese haplotypes including 1,781 CAD cases and 2,636 controls. We detected eight new susceptibility loci and Japanese-specific rare variants contributing to disease severity and increased cardiovascular mortality. We then conducted a trans-ancestry meta-analysis and discovered 35 additional new loci. Using the meta-analysis results, we derived a polygenic risk score (PRS) for CAD, which outperformed those derived from either Japanese or European genome-wide association studies. The PRS prioritized risk factors among various clinical parameters and segregated individuals with increased risk of long-term cardiovascular mortality. Our data improve the clinical characterization of CAD genetics and suggest the utility of trans-ancestry meta-analysis for PRS derivation in non-European populations.
- Published
- 2020