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

Kazuyoshi Ishigaki,Akihide Masumoto,Johji Inazawa,Takashi Kohno,Momoko Horikoshi,Satoshi Nagayama,Satoshi Asai,Tomoaki Fujioka,Atsushi Takahashi,Wataru Obara,Shiro Ikegawa,Taiki Yamaji,Nobuaki Sinozaki,Koichi Matsuda,Yukinori Okada,Naoko Minegishi,Tomomitsu Hirota,Hirokazu Uemura,Toshihiro Tanaka,Chikashi Terao,Eiryo Kawakami,Hidewaki Nakagawa,Makoto Hirata,Kazuaki Chayama,Kazuhisa Takahashi,Toshimasa Yamauchi,Yasuhiko Sakata,Takao Suzuki,Masaki Mori,Keitaro Tanaka,Norie Sawada,Hideki Yanai,Yukihiro Koretsune,Steven Gazal,Yusuke Nakamura,Daiki Miki,Takashi Kadowaki,Masayuki Yamamoto,Atsushi Shimizu,Yoichiro Kamatani,Takashi Takahashi,Toyomasa Katagiri,Nakao Iwata,Teruhiko Yoshida,Yataro Daigo,Yukihide Momozawa,Kozo Tanno,Shumpei Niida,Kouya Shiraishi,Mariko Naito,Michiaki Kubo,Satoshi Koyama,Motoki Iwasaki,Masato Akiyama,Saori Sakaue,Yoshinori Murakami,Makoto Sasaki,Hiroki Yamaguchi,Ryo Takata,Hiromu Kutsumi,Shoichiro Tsugane,Yoshio Miki,Kenji Wakai,Ken Suzuki,Yuta Kochi,Shiro Minami,Kichiya Suzuki,Ikuyo Kou,Soumya Raychaudhuri,Nana Matoba,Kouichi Ozaki,Yasuo Takahashi,Akari Suzuki,Osamu Ogawa,Kazuhiko Yamamoto,Masahiko Higashiyama,Masashi Ikeda,Shigeo Murayama,Issei Imoto,Masahiro Kanai,Hidemi Ito,Chizu Tanikawa,Tiffany Amariuta,Hiroki Sugishita,Yasushi Sakata,Mayumi Tamari,Katsuhiko Yamaji ,Kei Ito ,Siew Kee Low

doi:10.1038/s41588-020-0640-3

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 × 10-9). 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.

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