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PMID: 34594039 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A cross-population atlas of genetic associations for 220 human phenotypes.

Nature genetics ·Vol. 53 ·No. 10 ·2021-00-00 ·Pages 1415-1424

Sakaue S, Kanai M, Tanigawa Y, Karjalainen J, Kurki M, Koshiba S, Narita A, Konuma T, Yamamoto K, Akiyama M, Ishigaki K, Suzuki A, Suzuki K, Obara W, Yamaji K, Takahashi K, Asai S, Takahashi Y, Suzuki T, Shinozaki N, Yamaguchi H, Minami S, Murayama S, Yoshimori K, Nagayama S, Obata D, Higashiyama M, Masumoto A, Koretsune Y, FinnGen, Ito K, Terao C, Yamauchi T, Komuro I, Kadowaki T, Tamiya G, Yamamoto M, Nakamura Y, Kubo M, Murakami Y, Yamamoto K, Kamatani Y, Palotie A, Rivas MA, Daly MJ, Matsuda K, Okada Y

Abstract

Current genome-wide association studies do not yet capture sufficient diversity in populations and scope of phenotypes. To expand an atlas of genetic associations in non-European populations, we conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan (n = 179,000), by incorporating past medical history and text-mining of electronic medical records. Meta-analyses with the UK Biobank and FinnGen (ntotal = 628,000) identified ~5,000 new loci, which improved the resolution of the genomic map of human traits. This atlas elucidated the landscape of pleiotropy as represented by the major histocompatibility complex locus, where we conducted HLA fine-mapping. Finally, we performed statistical decomposition of matrices of phenome-wide summary statistics, and identified latent genetic components, which pinpointed responsible variants and biological mechanisms underlying current disease classifications across populations. The decomposed components enabled genetically informed subtyping of similar diseases (for example, allergic diseases). Our study suggests a potential avenue for hypothesis-free re-investigation of human diseases through genetics.

MeSH Terms
ABO Blood-Group System/genetics Biological Specimen Banks Genetic Association Studies Genetic Loci Genetic Pleiotropy Genetic Predisposition to Disease Genome-Wide Association Study Humans Major Histocompatibility Complex/genetics Meta-Analysis as Topic Mutation/genetics Phenotype
Chemicals
ABO Blood-Group System
Authors & Affiliations
47 authors, click to expand affiliations / ORCID
Sakaue Saori ORCID
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan. [email protected]. | Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. [email protected]. | Center for Data Sciences, Harvard Medical School, Boston, MA, USA. [email protected]. | Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. [email protected]. | Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. [email protected].
Kanai Masahiro ORCID
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan. | Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. | Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. | Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA. | Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. | Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Tanigawa Yosuke ORCID
Department of Biomedical Data Science, School of Medicine, Stanford University, Stanford, CA, USA.
Karjalainen Juha
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. | Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. | Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA. | Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Kurki Mitja
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. | Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. | Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA. | Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Koshiba Seizo
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan. | Advanced Research Center for Innovations in Next-Generation Medicine (INGEM), Sendai, Japan.
Narita Akira ORCID
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
Konuma Takahiro
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
Yamamoto Kenichi
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan. | Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan. | Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
Akiyama Masato
Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. | Department of Ocular Pathology and Imaging Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ishigaki Kazuyoshi ORCID
Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. | Center for Data Sciences, Harvard Medical School, Boston, MA, USA. | Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. | Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Suzuki Akari
Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Suzuki Ken ORCID
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
Obara Wataru
Department of Urology, Iwate Medical University, Iwate, Japan.
Yamaji Ken
Department of Internal Medicine and Rheumatology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Takahashi Kazuhisa
Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Asai Satoshi
Division of Pharmacology, Department of Biomedical Science, Nihon University School of Medicine, Tokyo, Japan. | Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, Japan.
Takahashi Yasuo ORCID
Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, Japan.
Suzuki Takao
Tokushukai Group, Tokyo, Japan.
Shinozaki Nobuaki
Tokushukai Group, Tokyo, Japan.
Yamaguchi Hiroki ORCID
Department of Hematology, Nippon Medical School, Tokyo, Japan.
Minami Shiro
Department of Bioregulation, Nippon Medical School, Kawasaki, Japan.
Murayama Shigeo
Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
Yoshimori Kozo
Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan.
Nagayama Satoshi
The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
Obata Daisuke
Center for Clinical Research and Advanced Medicine, Shiga University of Medical Science, Otsu, Japan.
Higashiyama Masahiko
Department of General Thoracic Surgery, Osaka International Cancer Institute, Osaka, Japan.
Masumoto Akihide
Aso Iizuka Hospital, Fukuoka, Japan.
Koretsune Yukihiro
National Hospital Organization Osaka National Hospital, Osaka, Japan.
FinnGen
Ito Kaoru ORCID
Laboratory for Cardiovascular Genomics and Informatics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Terao Chikashi ORCID
Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Yamauchi Toshimasa
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Komuro Issei ORCID
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Kadowaki Takashi
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. | Toranomon Hospital, Tokyo, Japan.
Tamiya Gen
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan. | Advanced Research Center for Innovations in Next-Generation Medicine (INGEM), Sendai, Japan. | Graduate School of Medicine, Tohoku University, Sendai, Japan. | Center for Advanced Intelligence Project, RIKEN, Tokyo, Japan.
Yamamoto Masayuki ORCID
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan. | Advanced Research Center for Innovations in Next-Generation Medicine (INGEM), Sendai, Japan. | Graduate School of Medicine, Tohoku University, Sendai, Japan.
Nakamura Yusuke
Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. | Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Kubo Michiaki ORCID
RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Murakami Yoshinori ORCID
Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yamamoto Kazuhiko
Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Kamatani Yoichiro
Laboratory for Statistical and Translational Genetics, 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.
Palotie Aarno ORCID
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. | Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. | Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Analytic and Translational Genetics Unit, Department of Medicine, and the Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Rivas Manuel A ORCID
Department of Biomedical Data Science, School of Medicine, Stanford University, Stanford, CA, USA.
Daly Mark J ORCID
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. | Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. | Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA. | Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Matsuda Koichi ORCID
Department of Computational Biology and Medical Sciences, Graduate school of Frontier Sciences, The University of Tokyo, Tokyo, Japan. [email protected].
Okada Yukinori ORCID
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan. [email protected]. | Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. [email protected]. | Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan. [email protected]. | Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Analytic and Translational Genetics Unit, Department of Medicine, and the Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. [email protected]. | Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan. [email protected].
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/s41588-021-00931-x
Email
[email protected]
[email protected]
[email protected]
Published
2021-00-00
Epub
2021-00-30
Pages
1415-1424
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC12208603
Subset
IM
Grants
Medical Research Council · MC_PC_17228 · United Kingdom
Medical Research Council · MC_QA137853 · United Kingdom
NHGRI NIH HHS · R01 HG010140 · United States
NHGRI NIH HHS · U01 HG009080 · United States
External Links
PubMed source DOI: 10.1038/s41588-021-00931-x PMC Full Text View journal details
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