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

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; Hideki Yanai; Akihide Masumoto; Yukihiro Koretsune; Hiromu Kutsumi; Masahiko Higashiyama; Shigeo Murayama; Naoko Minegishi; Kichiya Suzuki; Kozo Tanno; Atsushi Shimizu; Taiki Yamaji; Motoki Iwasaki; Norie Sawada; Hirokazu Uemura; Keitaro Tanaka; Mariko Naito; Makoto Sasaki; Kenji Wakai; Shoichiro Tsugane; Masayuki Yamamoto; Kazuhiko Yamamoto; Yoshinori Murakami; Yusuke Nakamura; Soumya Raychaudhuri; Johji Inazawa; Toshimasa Yamauchi; Takashi Kadowaki; Michiaki Kubo; Yoichiro Kamatani

doi:10.1038/s41588-020-0640-3

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

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 NiidaYasushi 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, Hideki Yanai, Akihide Masumoto, Yukihiro Koretsune, Hiromu Kutsumi, Masahiko Higashiyama, Shigeo Murayama, Naoko Minegishi, Kichiya Suzuki, Kozo Tanno, Atsushi Shimizu, Taiki Yamaji, Motoki Iwasaki, Norie Sawada, Hirokazu Uemura, Keitaro Tanaka, Mariko Naito, Makoto Sasaki, Kenji Wakai, Shoichiro Tsugane, Masayuki Yamamoto, Kazuhiko Yamamoto, Yoshinori Murakami, Yusuke Nakamura, Soumya Raychaudhuri, Johji Inazawa, Toshimasa Yamauchi, Takashi Kadowaki, Michiaki Kubo, Yoichiro Kamatani

Research output: Contribution to journal › Article › peer-review

77 Citations (Scopus)

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	https://doi.org/10.1038/s41588-020-0640-3
Publication status	Published - 2020 Jul 1

ASJC Scopus subject areas

Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41588-020-0640-3

Cite this

Ishigaki, K., Akiyama, M., Kanai, M., Takahashi, A., Kawakami, E., Sugishita, H., Sakaue, S., Matoba, N., Low, S. K., Okada, Y., Terao, C., Amariuta, T., Gazal, S., Kochi, Y., Horikoshi, M., Suzuki, K., Ito, K., Koyama, S., Ozaki, K., ... Kamatani, Y. (2020). Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases. Nature Genetics, 52(7), 669-679. https://doi.org/10.1038/s41588-020-0640-3

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

Ishigaki, K, Akiyama, M, Kanai, M, Takahashi, A, Kawakami, E, Sugishita, H, Sakaue, S, Matoba, N, Low, SK, Okada, Y, Terao, C, Amariuta, T, Gazal, S, Kochi, Y, Horikoshi, M, Suzuki, K, Ito, K, Koyama, S, Ozaki, K, Niida, S, Sakata, Y, Sakata, Y, Kohno, T, Shiraishi, K, Momozawa, Y, Hirata, M, Matsuda, K, Ikeda, M, Iwata, N, Ikegawa, S, Kou, I, Tanaka, T, Nakagawa, H, Suzuki, A, Hirota, T, Tamari, M, Chayama, K, Miki, D, Mori, M, Nagayama, S, Daigo, Y, Miki, Y, Katagiri, T, Ogawa, O, Obara, W, Ito, H, Yoshida, T, Imoto, I, Takahashi, T, Tanikawa, C, Suzuki, T, Sinozaki, N, Minami, S, Yamaguchi, H, Asai, S, Takahashi, Y, Yamaji, K, Takahashi, K, Fujioka, T, Takata, R, Yanai, H, Masumoto, A, Koretsune, Y, Kutsumi, H, Higashiyama, M, Murayama, S, Minegishi, N, Suzuki, K, Tanno, K, Shimizu, A, Yamaji, T, Iwasaki, M, Sawada, N, Uemura, H, Tanaka, K, Naito, M, Sasaki, M, Wakai, K, Tsugane, S, Yamamoto, M, Yamamoto, K, Murakami, Y, Nakamura, Y, Raychaudhuri, S, Inazawa, J, Yamauchi, T, Kadowaki, T, Kubo, M & Kamatani, Y 2020, 'Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases', Nature Genetics, vol. 52, no. 7, pp. 669-679. https://doi.org/10.1038/s41588-020-0640-3

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. / Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases. In: Nature Genetics. 2020 ; Vol. 52, No. 7. pp. 669-679.

@article{db718d8ec7d34a74ba1b7a113400c268,

title = "Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases",

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.",

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

note = "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: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2020",

month = jul,

day = "1",

doi = "10.1038/s41588-020-0640-3",

language = "English",

volume = "52",

pages = "669--679",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "7",

}

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 -

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

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this