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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-06-08

AUTHORS

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

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. More... »

PAGES

669-679

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    7

    VOLUME

    52

    Author Affiliations

  • Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
  • Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan
  • Artificial Intelligence Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
  • Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  • Department of Genetics and UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  • Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan
  • Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan
  • Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Graduate School of Arts and Sciences, Harvard University, Cambridge, MA, USA
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
  • Department of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
  • Laboratory for Genomics of Diabetes and Metabolism, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  • Laboratory for Cardiovascular Genomics and Informatics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Japan
  • Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
  • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Tohoku, Japan
  • Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan
  • Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
  • Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan
  • Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan
  • Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
  • Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan
  • Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Laboratory for Respiratory and Allergic Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
  • Department of Surgery and Sciences, Graduate School of Medicine, Kyushu University, Fukuoka, Japan
  • Department of Gastroenterological Surgery, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
  • Center for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Department of Genetic Diagnosis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
  • Division of Genome Medicine, Institute for Genome Research, Tokushima University, Tokushima, Japan
  • Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • Department of Urology, Iwate Medical University School of Medicine, Iwate, Japan
  • Division of Descriptive Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan
  • Division of Cancer Genetics, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Aichi Cancer Center, Nagoya, Japan
  • Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Tokushukai Group, Tokyo, Japan
  • Department of Bioregulation, Nippon Medical School, Kawasaki, Japan
  • Department of Hematology, Nippon Medical School, Tokyo, Japan
  • Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, Japan
  • Department of Internal Medicine and Rheumatology, Juntendo University Graduate School of Medicine, Tokyo, Japan
  • Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
  • Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan
  • Aso Iizuka Hospital, Fukuoka, Japan
  • National Hospital Organization Osaka National Hospital, Osaka, Japan
  • Center for Clinical Research and Advanced Medicine, Shiga University of Medical Science, Shiga, Japan
  • Department of General Thoracic Surgery, Osaka International Cancer Institute, Osaka, Japan
  • Department of Neurology and Neuropathology (the Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
  • Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
  • Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan
  • Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
  • College of Nursing Art and Science, University of Hyogo, Akashi, Japan
  • Department of Preventive Medicine, Saga University Faculty of Medicine, Saga, Japan
  • Department of Oral Epidemiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
  • Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
  • Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
  • Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan
  • RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-020-0640-3

    DOI

    http://dx.doi.org/10.1038/s41588-020-0640-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1128290071

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32514122


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