TY - JOUR
T1 - A cross-population atlas of genetic associations for 220 human phenotypes
AU - FinnGen
AU - Sakaue, Saori
AU - Kanai, Masahiro
AU - Tanigawa, Yosuke
AU - Karjalainen, Juha
AU - Kurki, Mitja
AU - Koshiba, Seizo
AU - Narita, Akira
AU - Konuma, Takahiro
AU - Yamamoto, Kenichi
AU - Akiyama, Masato
AU - Ishigaki, Kazuyoshi
AU - Suzuki, Akari
AU - Suzuki, Ken
AU - Obara, Wataru
AU - Yamaji, Ken
AU - Takahashi, Kazuhisa
AU - Asai, Satoshi
AU - Takahashi, Yasuo
AU - Suzuki, Takao
AU - Shinozaki, Nobuaki
AU - Yamaguchi, Hiroki
AU - Minami, Shiro
AU - Murayama, Shigeo
AU - Yoshimori, Kozo
AU - Nagayama, Satoshi
AU - Obata, Daisuke
AU - Higashiyama, Masahiko
AU - Masumoto, Akihide
AU - Koretsune, Yukihiro
AU - Ito, Kaoru
AU - Terao, Chikashi
AU - Yamauchi, Toshimasa
AU - Komuro, Issei
AU - Kadowaki, Takashi
AU - Tamiya, Gen
AU - Yamamoto, Masayuki
AU - Nakamura, Yusuke
AU - Kubo, Michiaki
AU - Murakami, Yoshinori
AU - Yamamoto, Kazuhiko
AU - Kamatani, Yoichiro
AU - Palotie, Aarno
AU - Rivas, Manuel A.
AU - Daly, Mark J.
AU - Matsuda, Koichi
AU - Okada, Yukinori
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
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U2 - 10.1038/s41588-021-00931-x
DO - 10.1038/s41588-021-00931-x
M3 - Article
C2 - 34594039
AN - SCOPUS:85116399963
SN - 1061-4036
VL - 53
SP - 1415
EP - 1424
JO - Nature genetics
JF - Nature genetics
IS - 10
ER -
