日本东京大学Issei Komuro和日本理化学研究所（RIKEN）Kaoru Ito小组合作，通过对特定人群和跨祖先人群的全基因组分析确定了冠状动脉疾病(CAD)特有和共享的遗传风险基因座。相关论文于2020年6月5日发表于国际学术期刊《自然-遗传学》。

为了阐明日本CAD患者的遗传学，研究人员利用新发布的包含1781名CAD患者和2,636名健康个体的单倍体参考数据集，对168228名日本人（25892例患者和142336例健康个体）通过基因型推算进行了大规模全基因组关联研究。研究人员检测到八个新的易感基因座和日本特有的罕见变异，这些变异增加了疾病的严重程度和心血管死亡率。

然后，通过跨祖先的荟萃分析，研究人员发现了35个新的新基因座。利用荟萃分析的结果，研究人员计算了CAD的多基因风险评分（PRS），该结果优于日本或欧洲全基因组关联研究得出的结果。在各种临床参数中PRS将危险因素放在了首要位置，并且将长期心血管疾病造成死亡的高风险个体区分出来。

该研究数据改善了CAD遗传学的临床特征，并证实了跨谱系荟萃分析在非欧洲人群中进行PRS的实用性。

附：英文原文

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

Author: 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 Sawada, Shoichiro 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

Issue&Volume: 2020-10-05

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. 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.

DOI: 10.1038/s41588-020-0705-3

Source: https://www.nature.com/articles/s41588-020-0705-3