1. A cross-population atlas of genetic associations for 220 human phenotypes
- Author
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Yukinori Okada, Hiroki Yamaguchi, Kazuyoshi Ishigaki, Shigeo Murayama, Yosuke Tanigawa, Gen Tamiya, Masayuki Yamamoto, Yoichiro Kamatani, Akihide Masumoto, Manuel A. Rivas, Yusuke Nakamura, Issei Komuro, Akira Narita, Masahiro Kanai, Ken Yamaji, Shiro Minami, Yasuo Takahashi, Toshimasa Yamauchi, Takahiro Konuma, Mark J. Daly, Yoshinori Murakami, Chikashi Terao, Koichi Matsuda, Kazuhisa Takahashi, Michiaki Kubo, Masahiko Higashiyama, Kaoru Ito, Saori Sakaue, Akari Suzuki, Nobuaki Shinozaki, Takao Suzuki, Satoshi Asai, Ken Suzuki, Kazuhiko Yamamoto, Takashi Kadowaki, Yukihiro Koretsune, Wataru Obara, Kenichi Yamamoto, Seizo Koshiba, Juha Karjalainen, Kozo Yoshimori, FinnGen, Daisuke Obata, Masato Akiyama, Satoshi Nagayama, Mitja I. Kurki, and Aarno Palotie
- Subjects
education.field_of_study ,Evolutionary biology ,Pleiotropy ,Population ,Genetics ,Locus (genetics) ,Human leukocyte antigen ,Disease ,Biology ,education ,Biobank ,Subtyping ,Genetic association - 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.
- Published
- 2021
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