@article{2779470709f142768f6dbb2be4631aab,
title = "Population-specific and trans-ancestry genome-wide analyses identify distinct and shared genetic risk loci for coronary artery disease",
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.",
author = "Satoshi Koyama and Kaoru Ito and Chikashi Terao and Masato Akiyama and Momoko Horikoshi and Yukihide Momozawa and Hiroshi Matsunaga and Hirotaka Ieki and Kouichi Ozaki and Yoshihiro Onouchi and Atsushi Takahashi and Seitaro Nomura and Hiroyuki Morita and Hiroshi Akazawa and Changhoon Kim and Seo, {Jeong sun} and Koichiro Higasa and Motoki Iwasaki and Taiki Yamaji and Norie Sawada and Shoichiro Tsugane and Teruhide Koyama and Hiroaki Ikezaki and Naoyuki Takashima and Keitaro Tanaka and Kokichi Arisawa and Kiyonori Kuriki and Mariko Naito and Kenji Wakai and Shinichiro Suna and Yasuhiko Sakata and Hiroshi Sato and Masatsugu Hori and Yasushi Sakata and Koichi Matsuda and Yoshinori Murakami and Hiroyuki Aburatani and Michiaki Kubo and Fumihiko Matsuda and Yoichiro Kamatani and Issei Komuro",
note = "Funding Information: We thank the staff of BBJ for their excellent assistance in collecting samples and clinical information. We thank the Nagahama, JPHC, J-MICC and OACIS studies for their invaluable contributions to the study. We are grateful to the CARDIoGRAMplusC4D investigators, P. van der Harst and N. Verweij, for making their data publicly available. We thank A. P. Morris for providing us with the MANTRA software and valuable advice. This research was funded by the Japan Agency for Medical Research and Development (AMED) under grant numbers JP20km0405209 (the GRIFIN project), JP20km0405209 and JP20ek0109487. The BBJ was supported by the Tailor-made Medical Treatment Program of the Ministry of Education, Culture, Sports, Science, and Technology and AMED. The JPHC study has been supported by the National Cancer Center Research and Development Fund since 2011 and was supported by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan from 1989 to 2010. The J-MICC study was supported by Grants-in-Aid for Scientific Research for Priority Areas of Cancer (no. 17015018) and Innovative Areas (no. 221S0001) and by Japan Society for the Promotion of Science (JSPS) KAKENHI grant nos. JP16H06277 from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The Nagahama study was supported by a JSPS Grant-in-Aid for Scientific Research (C), KAKENHI grant numbers JP17K07255 and JP17KT0125, and the Practical Research Project for Rare/ Intractable Diseases from AMED under grant numbers JP16ek0109070, JP18kk0205008, JP18kk0205001, JP19ek0109283 and JP19ek0109348. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = nov,
day = "1",
doi = "10.1038/s41588-020-0705-3",
language = "English",
volume = "52",
pages = "1169--1177",
journal = "Nature genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "11",
}