Journal Article

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

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

2020

Overview

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. Genome-wide association analyses in the Japanese population and trans-ancestry meta-analyses identify new risk loci for coronary artery disease. A polygenic risk score derived from these findings identifies individuals with increased risk of long-term cardiovascular mortality.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 38/22 / 38/23 / 38/43 / 38/56 / 38/61 / 631/208/457 / 692/699/75/2 / Adult / Aged / Agriculture / Alleles / Animal Genetics and Genomics / Biobanks / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cardiovascular disease / Cardiovascular diseases / Cholestanetriol 26-Monooxygenase - genetics / Chromosome Mapping / Coronary artery / Coronary artery disease / Coronary Artery Disease - genetics / Coronary Artery Disease - mortality / Coronary heart disease / Coronary vessels / Gene Function / Genes / Genetic analysis / Genetic aspects / Genetic Pleiotropy / Genetic Predisposition to Disease / Genetic research / Genetics / Genome-wide association studies / Genome-Wide Association Study / Genomes / Genotype / Genotypes / Haplotypes / Health risk assessment / Heart diseases / Human Genetics / Humans / Japan / Loci / Meta-analysis / Middle Aged / Mortality / Pedigree / Population / Population genetics / Precision medicine / Risk analysis / Risk Factors