Journal
NATURE GENETICS
Volume 53, Issue 10, Pages 1415-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41588-021-00931-x
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Funding
- Tailor-Made Medical Treatment program (the BioBank Japan Project) of the Ministry of Education, Culture, Sports, Science, and Technology (MEXT)
- Japan Agency for Medical Research and Development (AMED)
- Business Finland [HUS 4685/31/2016, UH 4386/31/2016]
- AbbVie
- AstraZeneca
- Biogen
- Celgene
- Genentech
- GSK
- MSD
- Pfizer
- Sanofi
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Kanae Foundation for the Promotion of Medical Science
- Astellas Foundation for Research on Metabolic Disorders
- JCR Grant for Promoting Basic Rheumatology
- Nakajima Foundation Fellowship
- Masason Foundation
- Funai Overseas Scholarship from the Funai Foundation for Information Technology
- Stanford University School of Medicine
- National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) [R01HG010140]
- NIH Center for Multi-and Cross-population Mapping of Mendelian and Complex Diseases grant [5U01 HG009080]
- Japan Society for the Promotion of Science (JSPS) KAKENHI [19H01021, 20K21834]
- AMED [JP21km0405211, JP21ek0109413, JP21ek0410075, JP21gm4010006, JP21km0405217]
- JST Moonshot RD [JPMJMS2021]
- Takeda Science Foundation
- Bioinformatics Initiative of Osaka University Graduate School of Medicine, Osaka University
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The study conducted deep-phenotype genome-wide association studies in BioBank Japan, identifying approximately 5,000 new loci and improving the resolution of the genomic map of human traits. By decomposing matrices of phenome-wide summary statistics, responsible variants and biological mechanisms underlying current disease classifications across populations were pinpointed.
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 (n(total) = 628,000) identified similar to 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.
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