TY - JOUR
T1 - Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases
AU - Kanai, Masahiro
AU - Akiyama, Masato
AU - Takahashi, Atsushi
AU - Matoba, Nana
AU - Momozawa, Yukihide
AU - Ikeda, Masashi
AU - Iwata, Nakao
AU - Ikegawa, Shiro
AU - Hirata, Makoto
AU - Matsuda, Koichi
AU - Kubo, Michiaki
AU - Okada, Yukinori
AU - Kamatani, Yoichiro
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Clinical measurements can be viewed as useful intermediate phenotypes to promote understanding of complex human diseases. To acquire comprehensive insights into the underlying genetics, here we conducted a genome-wide association study (GWAS) of 58 quantitative traits in 162,255 Japanese individuals. Overall, we identified 1,407 trait-associated loci (P < 5.0 × 10 -8 ), 679 of which were novel. By incorporating 32 additional GWAS results for complex diseases and traits in Japanese individuals, we further highlighted pleiotropy, genetic correlations, and cell-type specificity across quantitative traits and diseases, which substantially expands the current understanding of the associated genetics and biology. This study identified both shared polygenic effects and cell-type specificity, represented by the genetic links among clinical measurements, complex diseases, and relevant cell types. Our findings demonstrate that even without prior biological knowledge of cross-phenotype relationships, genetics corresponding to clinical measurements successfully recapture those measurements' relevance to diseases, and thus can contribute to the elucidation of unknown etiology and pathogenesis.
AB - Clinical measurements can be viewed as useful intermediate phenotypes to promote understanding of complex human diseases. To acquire comprehensive insights into the underlying genetics, here we conducted a genome-wide association study (GWAS) of 58 quantitative traits in 162,255 Japanese individuals. Overall, we identified 1,407 trait-associated loci (P < 5.0 × 10 -8 ), 679 of which were novel. By incorporating 32 additional GWAS results for complex diseases and traits in Japanese individuals, we further highlighted pleiotropy, genetic correlations, and cell-type specificity across quantitative traits and diseases, which substantially expands the current understanding of the associated genetics and biology. This study identified both shared polygenic effects and cell-type specificity, represented by the genetic links among clinical measurements, complex diseases, and relevant cell types. Our findings demonstrate that even without prior biological knowledge of cross-phenotype relationships, genetics corresponding to clinical measurements successfully recapture those measurements' relevance to diseases, and thus can contribute to the elucidation of unknown etiology and pathogenesis.
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U2 - 10.1038/s41588-018-0047-6
DO - 10.1038/s41588-018-0047-6
M3 - Article
C2 - 29403010
AN - SCOPUS:85041590577
SN - 1061-4036
VL - 50
SP - 390
EP - 400
JO - Nature Genetics
JF - Nature Genetics
IS - 3
ER -