Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases

Nat Genet. 2020 Jul;52(7):669-679. doi: 10.1038/s41588-020-0640-3. Epub 2020 Jun 8.


The overwhelming majority of participants in current genetic studies are of European ancestry. To elucidate disease biology in the East Asian population, we conducted a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 320 independent signals in 276 loci for 27 diseases, with 25 novel loci (P < 9.58 × 10-9). East Asian-specific missense variants were identified as candidate causal variants for three novel loci, and we successfully replicated two of them by analyzing independent Japanese cohorts; p.R220W of ATG16L2 (associated with coronary artery disease) and p.V326A of POT1 (associated with lung cancer). We further investigated enrichment of heritability within 2,868 annotations of genome-wide transcription factor occupancy, and identified 378 significant enrichments across nine diseases (false discovery rate < 0.05) (for example, NKX3-1 for prostate cancer). This large-scale GWAS in a Japanese population provides insights into the etiology of complex diseases and highlights the importance of performing GWAS in non-European populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease* / ethnology
  • Genetic Variation
  • Genome-Wide Association Study*
  • Humans
  • Inheritance Patterns
  • Japan
  • Male
  • Sex Factors
  • Transcription Factors / genetics


  • Transcription Factors