RT Journal Article
SR Electronic
T1 Population-specific and transethnic genome-wide analyses reveal distinct and shared genetic risks of coronary artery disease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 827550
DO 10.1101/827550
A1 Satoshi Koyama
A1 Kaoru Ito
A1 Chikashi Terao
A1 Masato Akiyama
A1 Momoko Horikoshi
A1 Yukihide Momozawa
A1 Hiroshi Matsunaga
A1 Hirotaka Ieki
A1 Kouichi Ozaki
A1 Yoshihiro Onouchi
A1 Atsushi Takahashi
A1 Seitaro Nomura
A1 Hiroyuki Morita
A1 Hiroshi Akazawa
A1 Changhoon Kim
A1 Jeong-sun Seo
A1 Koichiro Higasa
A1 Motoki Iwasaki
A1 Taiki Yamaji
A1 Norie Sawada
A1 Shoichiro Tsugane
A1 Teruhide Koyama
A1 Hiroaki Ikezaki
A1 Naoyuki Takashima
A1 Keitaro Tanaka
A1 Kokichi Arisawa
A1 Kiyonori Kuriki
A1 Mariko Naito
A1 Kenji Wakai
A1 Shinichiro Suna
A1 Yasuhiko Sakata
A1 Hiroshi Sato
A1 Masatsugu Hori
A1 Yasushi Sakata
A1 Koichi Matsuda
A1 Yoshinori Murakami
A1 Hiroyuki Aburatani
A1 Michiaki Kubo
A1 Fumihiko Matsuda
A1 Yoichiro Kamatani
A1 Issei Komuro
YR 2019
UL http://biorxiv.org/content/early/2019/11/16/827550.abstract
AB To elucidate the genetics of coronary artery disease (CAD) in the Japanese population, we conducted a large-scale genome-wide association study (GWAS) of 168,228 Japanese (25,892 cases and 142,336 controls) with genotype imputation using a newly developed reference panel of Japanese haplotypes including 1,782 CAD cases and 3,148 controls. We detected 9 novel disease-susceptibility loci and Japanese-specific rare variants contributing to disease severity and increased cardiovascular mortality. We then conducted a transethnic meta-analysis and discovered 37 additional novel loci. Using the result of the meta-analysis, we derived a polygenic risk score (PRS) for CAD, which outperformed those derived from either Japanese or European GWAS. The PRS prioritized risk factors among various clinical parameters and segregated individuals with increased risk of long-term cardiovascular mortality. Our data improves clinical characterization of CAD genetics and suggests the utility of transethnic meta-analysis for PRS derivation in non-European populations.