日本人群GWAS研究發現不同疾病的新型易感基因座
作者：
小柯機器人發布時間：2020/6/10 14:44:04
日本理化學研究所Yoichiro Kamatani等研究人員合作利用日本人群的大規模全基因組關聯研究確定了不同疾病的新型易感基因座。該項研究成果於2020年6月8日在線發表在《自然—遺傳學》雜誌上。
當前遺傳學研究的絕大多數參與者都是歐洲血統。為了闡明東亞人群的疾病生物學，研究人員對212453名日本人進行了42種疾病的全基因組關聯研究（GWAS）。研究人員在276個基因座中檢測到320個獨立信號，涉及27種疾病，其中25個是新的基因座（P<9.58×10-9）。
東亞特定的錯義變體被確定為三個新基因座的候選因果變體，研究人員通過分析獨立的日本隊列成功地複製了其中兩個。ATG16L2的p.R220W（與冠狀動脈疾病有關）和POT1的p.V326A（與肺癌有關）。
研究人員進一步調查了全基因組轉錄因子佔據的2868個注釋中的遺傳力富集，並在9種疾病中發現378個顯著富集（假髮現率<0.05），例如，針對前列腺癌的NKX3-1。日本人群中的這種大型GWAS提供了對複雜疾病病因學的了解，並強調了在非歐洲人群中進行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