Population-specific and trans-ancestry genome-wide analyses identify distinct and shared genetic risk loci for coronary artery disease

Satoshi Koyama, Kaoru Ito, Chikashi Terao, Masato Akiyama, Momoko Horikoshi, Yukihide Momozawa, Hiroshi Matsunaga, Hirotaka Ieki, Kouichi Ozaki, Yoshihiro Onouchi, Atsushi Takahashi, Seitaro Nomura, Hiroyuki Morita, Hiroshi Akazawa, Changhoon Kim, Jeong sun Seo, Koichiro Higasa, Motoki Iwasaki, Taiki Yamaji, Norie SawadaShoichiro Tsugane, Teruhide Koyama, Hiroaki Ikezaki, Naoyuki Takashima, Keitaro Tanaka, Kokichi Arisawa, Kiyonori Kuriki, Mariko Naito, Kenji Wakai, Shinichiro Suna, Yasuhiko Sakata, Hiroshi Sato, Masatsugu Hori, Yasushi Sakata, Koichi Matsuda, Yoshinori Murakami, Hiroyuki Aburatani, Michiaki Kubo, Fumihiko Matsuda, Yoichiro Kamatani, Issei Komuro

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1169-1177
Number of pages9
JournalNature Genetics
Volume52
Issue number11
DOIs
Publication statusPublished - 2020 Nov 1

ASJC Scopus subject areas

  • Genetics

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