Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases

Nat Genet. 2018 Mar;50(3):390-400. doi: 10.1038/s41588-018-0047-6. Epub 2018 Feb 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People / genetics*
  • Asian People / statistics & numerical data
  • Cell Lineage / genetics*
  • Disease / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genetics, Population
  • Genome-Wide Association Study / methods
  • Humans
  • Japan / epidemiology
  • Male
  • Multifactorial Inheritance / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci*
  • Sequence Analysis, DNA