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Meta-Analysis
. 2020 Nov;52(11):1169-1177.
doi: 10.1038/s41588-020-0705-3. Epub 2020 Oct 5.

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

Satoshi Koyama  1 , Kaoru Ito  2 , Chikashi Terao  3 , Masato Akiyama  3   4 , Momoko Horikoshi  5 , Yukihide Momozawa  6 , Hiroshi Matsunaga  1   7 , Hirotaka Ieki  1   7 , Kouichi Ozaki  1   8 , Yoshihiro Onouchi  1   9 , Atsushi Takahashi  3   10 , Seitaro Nomura  7   11 , Hiroyuki Morita  7 , Hiroshi Akazawa  7 , Changhoon Kim  12 , Jeong-Sun Seo  12   13 , Koichiro Higasa  14   15 , Motoki Iwasaki  16 , Taiki Yamaji  16 , Norie Sawada  16 , Shoichiro Tsugane  17 , Teruhide Koyama  18 , Hiroaki Ikezaki  19 , Naoyuki Takashima  20   21 , Keitaro Tanaka  22 , Kokichi Arisawa  23 , Kiyonori Kuriki  24 , Mariko Naito  25   26 , Kenji Wakai  26 , Shinichiro Suna  27 , Yasuhiko Sakata  28 , Hiroshi Sato  29 , Masatsugu Hori  30 , Yasushi Sakata  27 , Koichi Matsuda  31 , Yoshinori Murakami  32 , Hiroyuki Aburatani  11 , Michiaki Kubo  33 , Fumihiko Matsuda  15 , Yoichiro Kamatani  34   35   36 , Issei Komuro  37
Affiliations
Meta-Analysis

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

Satoshi Koyama et al. Nat Genet. 2020 Nov.

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.

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