Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population

Nat Genet. 2019 Mar;51(3):379-386. doi: 10.1038/s41588-018-0332-4. Epub 2019 Feb 4.

Abstract

To understand the genetics of type 2 diabetes in people of Japanese ancestry, we conducted A meta-analysis of four genome-wide association studies (GWAS; 36,614 cases and 155,150 controls of Japanese ancestry). We identified 88 type 2 diabetes-associated loci (P < 5.0 × 10-8) with 115 independent signals (P < 5.0 × 10-6), of which 28 loci with 30 signals were novel. Twenty-eight missense variants were in linkage disequilibrium (r2 > 0.6) with the lead variants. Among the 28 missense variants, three previously unreported variants had distinct minor allele frequency (MAF) spectra between people of Japanese and European ancestry (MAFJPN > 0.05 versus MAFEUR < 0.01), including missense variants in genes related to pancreatic acinar cells (GP2) and insulin secretion (GLP1R). Transethnic comparisons of the molecular pathways identified from the GWAS results highlight both ethnically shared and heterogeneous effects of a series of pathways on type 2 diabetes (for example, monogenic diabetes and beta cells).

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asians / genetics*
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Gene Frequency / genetics
  • Genetic Loci / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study / methods
  • Genotype
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Whites / genetics