New Results
Large scale genome-wide association study in a Japanese population identified 45 novel susceptibility loci for 22 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, 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: https://doi.org/10.1101/795948
Kazuyoshi Ishigaki
1Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
2Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
3Center for Data Sciences, Harvard Medical School, Boston, MA 02115, USA
4Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Masato Akiyama
1Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
5Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University. Fukuoka, Japan
Masahiro Kanai
1Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
4Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
6Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
Atsushi Takahashi
1Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
7Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan
Eiryo Kawakami
8Healthcare and Medical Data Driven AI based Predictive Reasoning Development Unit, Medical Sciences Innovation Hub Program (MIH), RIKEN, Yokohama, Japan
9Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Hiroki Sugishita
9Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Saori Sakaue
1Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
10Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan
11Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
Nana Matoba
1Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
12Department of Genetics & UNC Neuroscience Center, University of North Carolina at Chapel Hill, NC, USA
Siew-Kee Low
1Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
13Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan
Yukinori Okada
1Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
10Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan
14Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, Japan
15Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan
Chikashi Terao
16Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Tiffany Amariuta
2Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
3Center for Data Sciences, Harvard Medical School, Boston, MA 02115, USA
4Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
6Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
17Graduate School of Arts and Sciences, Harvard University, Cambridge, MA 02138, USA
Steven Gazal
4Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
18Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
Yuta Kochi
19Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Momoko Horikoshi
20Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Ken Suzuki
1Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
10Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan
20Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
21Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Kaoru Ito
22Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Yukihide Momozawa
23Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Makoto Hirata
24Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Koichi Matsuda
25Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
Masashi Ikeda
26Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan
Nakao Iwata
26Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan
Shiro Ikegawa
27Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Ikuyo Kou
27Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Toshihiro Tanaka
22Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
28Department of Human Genetics and Disease Diversity, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan
Hidewaki Nakagawa
29Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan
Akari Suzuki
19Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Tomomitsu Hirota
30Laboratory for Respiratory and Allergic Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Mayumi Tamari
30Laboratory for Respiratory and Allergic Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Kazuaki Chayama
31Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
Daiki Miki
31Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
Masaki Mori
32Department of Gastroenterological Surgery Graduate School of Medicine, Osaka University, Osaka, Japan
Satoshi Nagayama
33Department of Gastroenterological Surgery, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
Yataro Daigo
34Department of Medical Oncology and Cancer Center, and Center for Advanced Medicine against Cancer, Shiga University of Medical Science, Shiga, Japan
35Center for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Yoshio Miki
36Department of Genetic Diagnosis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
Toyomasa Katagiri
37Division of Genome Medicine, Institute for Genome Research, Tokushima University, Tokushima, Japan
Osamu Ogawa
38Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Wataru Obara
39Department of Urology, Iwate Medical University School of Medicine, Iwate, Japan
Hidemi Ito
40Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan
41Division of Descriptive Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Teruhiko Yoshida
42Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan
Issei Imoto
43Division of Molecular Genetics, Aichi Cancer Center Research Institute, Nagoya, Japan
44Risk Assessment Center, Aichi Caner Center Hospital, Nagoya, Japan
45Division of Cancer Genetics, Graduate School of Medicine, Nagoya University, Nagoya, Japan
Takashi Takahashi
46Aichi Cancer Center, Nagoya, Japan
Chizu Tanikawa
47Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Takao Suzuki
48Tokushukai Group, Tokyo, Japan
Nobuaki Sinozaki
48Tokushukai Group, Tokyo, Japan
Shiro Minami
49Department of Bioregulation, Nippon Medical School, Tokyo, Japan
Hiroki Yamaguchi
50Department of Hematology, Nippon Medical School, Tokyo, Japan
Satoshi Asai
51Division of Pharmacology, Department of Biomedical Science, Nihon University School of Medicine, Tokyo, Japan
52Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, Japan
Yasuo Takahashi
52Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, Japan
Ken Yamaji
53Department of Internal Medicine and Rheumatology, Juntendo University Graduate School of Medicine, Tokyo, Japan
Kazuhisa Takahashi
54Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
Tomoaki Fujioka
39Department of Urology, Iwate Medical University School of Medicine, Iwate, Japan
Ryo Takata
39Department of Urology, Iwate Medical University School of Medicine, Iwate, Japan
Hideki Yanai
55Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan
Akihide Masumoto
56Aso Iizuka Hospital, Fukuoka, Japan
Yukihiro Koretsune
57National Hospital Organization Osaka National Hospital, Osaka, Japan
Hiromu Kutsumi
58Center for Clinical Research and Advanced Medicine, Shiga University of Medical Science, Shiga, Japan
Masahiko Higashiyama
59Department of General Thoracic Surgery, Osaka International Cancer Institute, Osaka, Japan
Shigeo Murayama
60Department of Neurology and Neuropathology (the Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
Naoko Minegishi
61Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Kichiya Suzuki
61Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Kozo Tanno
62Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan
Atsushi Shimizu
62Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan
Taiki Yamaji
63Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
Motoki Iwasaki
63Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
Norie Sawada
63Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
Hirokazu Uemura
64Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
Keitaro Tanaka
65Department of Preventive Medicine, Saga University Faculty of Medicine, Saga, Japan
Mariko Naito
66Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
67Department of Oral Epidemiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
Makoto Sasaki
62Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan
Kenji Wakai
66Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
Shoichiro Tsugane
68Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
Masayuki Yamamoto
61Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Kazuhiko Yamamoto
19Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Yoshinori Murakami
69Division of Molecular Pathology, The Institute of Medical Sciences, The University of Tokyo, Tokyo, Japan
Yusuke Nakamura
70Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo, Japan
Soumya Raychaudhuri
2Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
3Center for Data Sciences, Harvard Medical School, Boston, MA 02115, USA
4Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
6Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
17Graduate School of Arts and Sciences, Harvard University, Cambridge, MA 02138, USA
71Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
Johji Inazawa
72Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
73Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan
Toshimasa Yamauchi
21Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Takashi Kadowaki
21Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Michiaki Kubo
74RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Yoichiro Kamatani
1Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
75Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
INTRODUCTORY PARAGRAPH
The overwhelming majority of participants in current genetic studies are of European ancestry1–3, limiting our genetic understanding of complex disease in non-European populations. To address this, we aimed to elucidate polygenic disease biology in the East Asian population by conducting a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 383 independent signals in 331 loci for 30 diseases, among which 45 loci were novel (P < 5 × 10−8). Compared with known variants, novel variants have lower frequency in European populations but comparable frequency in East Asian populations, suggesting the advantage of this study in discovering these novel variants. Three novel signals were in linkage disequilibrium (r2 > 0.6) with missense variants which are monomorphic in European populations (1000 Genomes Project) including rs11235604(p.R220W of ATG16L2, a autophagy-related gene) associated with coronary artery disease. We further investigated enrichment of heritability within 2,868 annotations of genome-wide transcription factor occupancy, andidentified 378 significant enrichments across nine diseases (FDR < 0.05) (e.g. NF-κB for immune-related diseases). This large-scale GWAS in a Japanese population provides insights into the etiology of common complex diseases and highlights the importance of performing GWAS in non-European populations.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Posted October 08, 2019.
Large scale genome-wide association study in a Japanese population identified 45 novel susceptibility loci for 22 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, 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
bioRxiv 795948; doi: https://doi.org/10.1101/795948
Large scale genome-wide association study in a Japanese population identified 45 novel susceptibility loci for 22 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, 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
bioRxiv 795948; doi: https://doi.org/10.1101/795948
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