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日本人群GWAS研究发现不同疾病的新型易感基因座
作者:小柯机器人 发布时间:2020/6/10 14:44:04

日本理化学研究所Yoichiro Kamatani等研究人员合作利用日本人群的大规模全基因组关联研究确定了不同疾病的新型易感基因座。该项研究成果于2020年6月8日在线发表在《自然—遗传学》杂志上。

当前遗传学研究的绝大多数参与者都是欧洲血统。为了阐明东亚人群的疾病生物学,研究人员对212453名日本人进行了42种疾病的全基因组关联研究(GWAS)。研究人员在276个基因座中检测到320个独立信号,涉及27种疾病,其中25个是新的基因座(P<9.58×10-9)。
 
东亚特定的错义变体被确定为三个新基因座的候选因果变体,研究人员通过分析独立的日本队列成功地复制了其中两个。ATG16L2的p.R220W(与冠状动脉疾病有关)和POT1的p.V326A(与肺癌有关)。
 
研究人员进一步调查了全基因组转录因子占据的2868个注释中的遗传力富集,并在9种疾病中发现378个显着富集(假发现率<0.05),例如,针对前列腺癌的NKX3-1。日本人群中的这种大型GWAS提供了对复杂疾病病因学的了解,并强调了在非欧洲人群中进行GWAS的重要性。
 
附:英文原文

Title: Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases

Author: Kazuyoshi Ishigaki, Masato Akiyama, Masahiro Kanai, Atsushi Takahashi, Eiryo Kawakami, Hiroki Sugishita, Saori Sakaue, Nana Matoba, Siew-Kee Low, Yukinori Okada, Chikashi Terao, Tiffany Amariuta, Steven Gazal, Yuta Kochi, Momoko Horikoshi, Ken Suzuki, Kaoru Ito, Satoshi Koyama, Kouichi Ozaki, Shumpei Niida, Yasushi Sakata, Yasuhiko Sakata, Takashi Kohno, Kouya Shiraishi, Yukihide Momozawa, Makoto Hirata, Koichi Matsuda, Masashi Ikeda, Nakao Iwata, Shiro Ikegawa, Ikuyo Kou, Toshihiro Tanaka, Hidewaki Nakagawa, Akari Suzuki, Tomomitsu Hirota, Mayumi Tamari, Kazuaki Chayama, Daiki Miki, Masaki Mori, Satoshi Nagayama, Yataro Daigo, Yoshio Miki, Toyomasa Katagiri, Osamu Ogawa, Wataru Obara, Hidemi Ito, Teruhiko Yoshida, Issei Imoto, Takashi Takahashi, Chizu Tanikawa, Takao Suzuki, Nobuaki Sinozaki, Shiro Minami, Hiroki Yamaguchi, Satoshi Asai, Yasuo Takahashi, Ken Yamaji, Kazuhisa Takahashi, Tomoaki Fujioka, Ryo Takata

Issue&Volume: 2020-06-08

Abstract: The overwhelming majority of participants in current genetic studies are of European ancestry. To elucidate disease biology in the East Asian population, we conducted a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 320 independent signals in 276 loci for 27 diseases, with 25 novel loci (P<9.58×109). East Asian–specific missense variants were identified as candidate causal variants for three novel loci, and we successfully replicated two of them by analyzing independent Japanese cohorts; p.R220W of ATG16L2 (associated with coronary artery disease) and p.V326A of POT1 (associated with lung cancer). We further investigated enrichment of heritability within 2,868 annotations of genome-wide transcription factor occupancy, and identified 378 significant enrichments across nine diseases (false discovery rate<0.05) (for example, NKX3-1 for prostate cancer). This large-scale GWAS in a Japanese population provides insights into the etiology of complex diseases and highlights the importance of performing GWAS in non-European populations.

DOI: 10.1038/s41588-020-0640-3

Source: https://www.nature.com/articles/s41588-020-0640-3

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex