| Literature DB >> 34594039 |
Saori Sakaue1,2,3,4,5, Masahiro Kanai6,7,8,9,10,11, Yosuke Tanigawa12, Juha Karjalainen7,8,9,11, Mitja Kurki7,8,9,11, Seizo Koshiba13,14, Akira Narita13, Takahiro Konuma6, Kenichi Yamamoto6,15,16, Masato Akiyama17,18, Kazuyoshi Ishigaki17,19,20,7, Akari Suzuki21, Ken Suzuki6, Wataru Obara22, Ken Yamaji23, Kazuhisa Takahashi24, Satoshi Asai25,26, Yasuo Takahashi26, Takao Suzuki27, Nobuaki Shinozaki27, Hiroki Yamaguchi28, Shiro Minami29, Shigeo Murayama30, Kozo Yoshimori31, Satoshi Nagayama32, Daisuke Obata33, Masahiko Higashiyama34, Akihide Masumoto35, Yukihiro Koretsune36, Kaoru Ito37, Chikashi Terao17, Toshimasa Yamauchi38, Issei Komuro39, Takashi Kadowaki38,40, Gen Tamiya13,14,41,42, Masayuki Yamamoto13,14,41, Yusuke Nakamura43,44, Michiaki Kubo45, Yoshinori Murakami46, Kazuhiko Yamamoto21, Yoichiro Kamatani17,47, Aarno Palotie7,11,48, Manuel A Rivas12, Mark J Daly7,8,9,11, Koichi Matsuda49, Yukinori Okada50,51,52,53,54.
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.Entities:
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Year: 2021 PMID： 34594039 DOI： 10.1038/s41588-021-00931-x
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330