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

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)...

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Vydáno v:	Nature genetics Ročník 53; číslo 10; s. 1415 - 1424
Hlavní autoři:	Sakaue, Saori, Kanai, Masahiro, Tanigawa, Yosuke, Karjalainen, Juha, Kurki, Mitja, Koshiba, Seizo, Narita, Akira, Konuma, Takahiro, Yamamoto, Kenichi, Akiyama, Masato, Ishigaki, Kazuyoshi, Suzuki, Akari, Suzuki, Ken, Obara, Wataru, Yamaji, Ken, Takahashi, Kazuhisa, Asai, Satoshi, Takahashi, Yasuo, Suzuki, Takao, Shinozaki, Nobuaki, Yamaguchi, Hiroki, Minami, Shiro, Murayama, Shigeo, Yoshimori, Kozo, Nagayama, Satoshi, Obata, Daisuke, Higashiyama, Masahiko, Masumoto, Akihide, Koretsune, Yukihiro, Ito, Kaoru, Terao, Chikashi, Yamauchi, Toshimasa, Komuro, Issei, Kadowaki, Takashi, Tamiya, Gen, Yamamoto, Masayuki, Nakamura, Yusuke, Kubo, Michiaki, Murakami, Yoshinori, Yamamoto, Kazuhiko, Kamatani, Yoichiro, Palotie, Aarno, Rivas, Manuel A., Daly, Mark J., Matsuda, Koichi, Okada, Yukinori
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.10.2021 Nature Publishing Group
Témata:	45/23 45/43 45/61 631/114/2785 631/208/205/2138 692/308/2056 ABO Blood-Group System - genetics Agriculture Allergic diseases Animal Genetics and Genomics Biobanks Biological Specimen Banks Biomarkers Biomedical and Life Sciences Biomedicine Cancer Research Classification Data mining Decomposition Disease Electronic health records Electronic medical records Gene Function Gene mapping Genetic Association Studies Genetic Loci Genetic Pleiotropy Genetic Predisposition to Disease Genetic research Genetics Genome-wide association studies Genome-Wide Association Study Genomes Genotype & phenotype Histocompatibility antigen HLA Human Genetics Humans Loci Major histocompatibility complex Major Histocompatibility Complex - genetics Medical records Meta-Analysis as Topic Mutation - genetics Pathogenesis Phenotype Phenotypes Pleiotropy Population Population genetics Populations Tuberculosis Ulcers Japan United Kingdom > UK
ISSN:	1061-4036, 1546-1718, 1546-1718
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Popis
Shrnutí:	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 ~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. Genome-wide analyses in BioBank Japan, UK Biobank and FinnGen identify ~5,000 new loci associated with 220 human traits. Statistical decomposition of matrices of phenome-wide summary statistics further highlights variants underpinning diseases across populations.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Author Contributions S.S., M. Kanai, and Y.O. conceived the study. S.S., M. Kanai, Y. Tanigawa., M.A.R., and Y.O. wrote the manuscript. S.S., M. Kanai, J.K., M. Kurki, T.Konuma, Kenichi Yamamoto, M.A., K.Ishigaki, Kazuhiko Yamamoto, Y. Kamatani, A.P., M.J.D., and Y.O. conducted GWAS data analysis. S.S., Y. Tanigawa., and M.A.R. conducted statistical decomposition analysis. S.S., S.T., A.N., G.T., and Y.O. conducted metabolome analysis. A.S., K.S., W.O., Ken Yamaji, K.T., S.A., Y.Takahashi, T.S., N.S., H.Y., S.Minami, S.Murayama, Kozo Yoshimori, S.N., D.O., M.H., A.M., Y.Koretsune, K.Ito, C.T., T.Y., I.K., T.Kadowaki, M.Y., Y.N., M.Kubo, Y.M., Kazuhiko Yamamoto, and K.M. collected and managed samples and data. A.P. and M.J.D. coordinated collaboration with FinnGen.
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/s41588-021-00931-x