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.
Original language | English |
---|---|
Pages (from-to) | 669-679 |
Number of pages | 11 |
Journal | Nature Genetics |
Volume | 52 |
Issue number | 7 |
DOIs | |
Publication status | Published - 2020 Jul 1 |
ASJC Scopus subject areas
- Genetics
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Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases. / 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.
In: Nature Genetics, Vol. 52, No. 7, 01.07.2020, p. 669-679.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases
AU - Ishigaki, Kazuyoshi
AU - Akiyama, Masato
AU - Kanai, Masahiro
AU - Takahashi, Atsushi
AU - Kawakami, Eiryo
AU - Sugishita, Hiroki
AU - Sakaue, Saori
AU - Matoba, Nana
AU - Low, Siew Kee
AU - Okada, Yukinori
AU - Terao, Chikashi
AU - Amariuta, Tiffany
AU - Gazal, Steven
AU - Kochi, Yuta
AU - Horikoshi, Momoko
AU - Suzuki, Ken
AU - Ito, Kaoru
AU - Koyama, Satoshi
AU - Ozaki, Kouichi
AU - Niida, Shumpei
AU - Sakata, Yasushi
AU - Sakata, Yasuhiko
AU - Kohno, Takashi
AU - Shiraishi, Kouya
AU - Momozawa, Yukihide
AU - Hirata, Makoto
AU - Matsuda, Koichi
AU - Ikeda, Masashi
AU - Iwata, Nakao
AU - Ikegawa, Shiro
AU - Kou, Ikuyo
AU - Tanaka, Toshihiro
AU - Nakagawa, Hidewaki
AU - Suzuki, Akari
AU - Hirota, Tomomitsu
AU - Tamari, Mayumi
AU - Chayama, Kazuaki
AU - Miki, Daiki
AU - Mori, Masaki
AU - Nagayama, Satoshi
AU - Daigo, Yataro
AU - Miki, Yoshio
AU - Katagiri, Toyomasa
AU - Ogawa, Osamu
AU - Obara, Wataru
AU - Ito, Hidemi
AU - Yoshida, Teruhiko
AU - Imoto, Issei
AU - Takahashi, Takashi
AU - Tanikawa, Chizu
AU - Suzuki, Takao
AU - Sinozaki, Nobuaki
AU - Minami, Shiro
AU - Yamaguchi, Hiroki
AU - Asai, Satoshi
AU - Takahashi, Yasuo
AU - Yamaji, Ken
AU - Takahashi, Kazuhisa
AU - Fujioka, Tomoaki
AU - Takata, Ryo
AU - Yanai, Hideki
AU - Masumoto, Akihide
AU - Koretsune, Yukihiro
AU - Kutsumi, Hiromu
AU - Higashiyama, Masahiko
AU - Murayama, Shigeo
AU - Minegishi, Naoko
AU - Suzuki, Kichiya
AU - Tanno, Kozo
AU - Shimizu, Atsushi
AU - Yamaji, Taiki
AU - Iwasaki, Motoki
AU - Sawada, Norie
AU - Uemura, Hirokazu
AU - Tanaka, Keitaro
AU - Naito, Mariko
AU - Sasaki, Makoto
AU - Wakai, Kenji
AU - Tsugane, Shoichiro
AU - Yamamoto, Masayuki
AU - Yamamoto, Kazuhiko
AU - Murakami, Yoshinori
AU - Nakamura, Yusuke
AU - Raychaudhuri, Soumya
AU - Inazawa, Johji
AU - Yamauchi, Toshimasa
AU - Kadowaki, Takashi
AU - Kubo, Michiaki
AU - Kamatani, Yoichiro
N1 - Funding Information: We acknowledge the staff of the BBJ for their outstanding assistance. We express our heartfelt gratitude to the Tohoku Medical Megabank Organization (Tohoku University), Iwate Tohoku Medical Megabank Organization (Iwate Medical University), Japan Public Health Center-based Prospective Study, Japan Multi-Institutional Collaborative Cohort Study and NCGG Biobank for their invaluable contributions to collecting control samples. We also express our gratitude to the OACIS for contributing to the replication study of CAD, and the National Cancer Center Hospital for contributing to the replication study of lung cancer. We also express our gratitude to E.K. and H.S. for kindly sharing their results of chromatin immunoprecipitation sequencing data analysis. We extend our appreciation to Y. Yukawa, Y. Yokoyama and other members of the Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences for great support. This research was supported by the Tailor-Made Medical Treatment Program (BBJ) of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), the Japan Agency for Medical Research and Development (AMED) under grant numbers JP17km0305002 (to M.Kubo) and JP17km0305001 (to M.M., S.Nagayama, Y.D., Y.Miki, T.Katagiri, O.O., W.O., H.I., T.Yoshida, I.I., T.Takahashi, J.I. and K.M.), JST KAKENHI grants (18H02932 to S.I.) and the Research Program on Hepatitis from AMED (JP19fk0310109 and JP19fk0210020 to K.C.). The Tohoku Medical Megabank Organization (Tohoku University) was supported in part by MEXT-JST and AMED, the most recent grant numbers being JP19km0105001 and JP19km0105002 (to M.Y.). The Iwate Tohoku Medical Megabank Organization (Iwate Medical University) was supported in part by MEXT-JST and AMED, the most recent grant numbers being JP19km0105003 and JP19km0105004. The Japan Public Health Center Prospective Study has been supported by the National Cancer Center Research and Development Fund since 2011 (latest grant number: 29-A-4, to S.T.) and was supported by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan from 1989–2010. The Japan Multi-Institutional Collaborative Cohort Study was supported by Grants-in-Aid for Scientific Research for Priority Areas of Cancer (17015018 to Nobuyuki Hamajima) and Innovative Areas (221S0001 to Hideo Tanaka) and by Japan Society for the Promotion of Science KAKENHI grants (CoBiA and 16H06277) from MEXT (to Hideo Tanaka and K.W.). The NCGG study was partly supported by AMED under grant number JP18kk0205009 (S.Niida) and JP20dk0207045 (K.O.). The OACIS was supported by AMED (JP19ek0210081 to Yasuhiko Sakata). The lung cancer study at the National Cancer Center Hospital was supported by the National Cancer Center Research and Development Fund (NCC Biobank), AMED (JP16ck0106096 to T.Kohno) and the Ministry of Health, Labour and Welfare program (H29-Gantaisaku-Ippann-025 to T.Kohno). The study at Fujita Health University was supported by AMED under grant numbers JP20dm0107097 (M.Ikeda and N.I.), JP20km0405201 (N.I.) and JP20km0405208 (M.Ikeda). Publisher Copyright: © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85086164787&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086164787&partnerID=8YFLogxK
U2 - 10.1038/s41588-020-0640-3
DO - 10.1038/s41588-020-0640-3
M3 - Article
C2 - 32514122
AN - SCOPUS:85086164787
VL - 52
SP - 669
EP - 679
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 7
ER -