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Ishigaki, Kazuyoshi; Akiyama, Masato; Kanai, Masahiro; Takahashi, Atsushi; Kawakami, Eiryo; Sugishita, Hiroki; Sakaue, Saori; Matoba, Nana; Low, Siew-Kee; Okada, Yukinori; Terao, Chikashi; Amariuta, Tiffany; Gazal, Steven; Kochi, Yuta; Horikoshi, Momoko; Suzuki, Ken; Ito, Kaoru; Koyama, Satoshi; Ozaki, Kouichi; Niida, Shumpei; Sakata, Yasushi; Sakata, Yasuhiko; Kohno, Takashi; Shiraishi, Kouya; Momozawa, Yukihide; Hirata, Makoto; Matsuda, Koichi; Ikeda, Masashi; Iwata, Nakao; Ikegawa, Shiro; Kou, Ikuyo; Tanaka, Toshihiro; Nakagawa, Hidewaki; Suzuki, Akari; Hirota, Tomomitsu; Tamari, Mayumi; Chayama, Kazuaki; Miki, Daiki; Mori, Masaki; Nagayama, Satoshi; Daigo, Yataro; Miki, Yoshio; Katagiri, Toyomasa; Ogawa, Osamu; Obara, Wataru; Ito, Hidemi; Yoshida, Teruhiko; Imoto, Issei; Takahashi, Takashi; Tanikawa, Chizu; Suzuki, Takao; Sinozaki, Nobuaki; Minami, Shiro; Yamaguchi, Hiroki; Asai, Satoshi; Takahashi, Yasuo; Yamaji, Ken; Takahashi, Kazuhisa; Fujioka, Tomoaki; Takata, Ryo; Yanai, Hideki; Masumoto, Akihide; Koretsune, Yukihiro; Kutsumi, Hiromu; Higashiyama, Masahiko; Murayama, Shigeo; Minegishi, Naoko; Suzuki, Kichiya; Tanno, Kozo; Shimizu, Atsushi; Yamaji, Taiki; Iwasaki, Motoki; Sawada, Norie; Uemura, Hirokazu; Tanaka, Keitaro; Naito, Mariko; Sasaki, Makoto; Wakai, Kenji; Tsugane, Shoichiro; Yamamoto, Masayuki; Yamamoto, Kazuhiko; Murakami, Yoshinori; Nakamura, Yusuke; Raychaudhuri, Soumya; Inazawa, Johji; Yamauchi, Toshimasa; Kadowaki, Takashi; Kubo, Michiaki; Kamatani, Yoichiro
Nature genetics, 07/2020, Volume: 52, Issue: 7Journal Article
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 ). 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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