Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population

Nat Genet. 2019 Mar;51(3):470-480. doi: 10.1038/s41588-018-0336-0. Epub 2019 Jan 28.


To perform detailed fine-mapping of the major-histocompatibility-complex region, we conducted next-generation sequencing (NGS)-based typing of the 33 human leukocyte antigen (HLA) genes in 1,120 individuals of Japanese ancestry, providing a high-resolution allele catalog and linkage-disequilibrium structure of both classical and nonclassical HLA genes. Together with population-specific deep-whole-genome-sequencing data (n = 1,276), we conducted NGS-based HLA, single-nucleotide-variant and indel imputation of large-scale genome-wide-association-study data from 166,190 Japanese individuals. A phenome-wide association study assessing 106 clinical phenotypes identified abundant, significant genotype-phenotype associations across 52 phenotypes. Fine-mapping highlighted multiple association patterns conferring independent risks from classical HLA genes. Region-wide heritability estimates and genetic-correlation network analysis elucidated the polygenic architecture shared across the phenotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asians / genetics*
  • Cell Line
  • Genetic Association Studies / methods
  • Genome-Wide Association Study / methods
  • Genotype
  • Humans
  • Linkage Disequilibrium / genetics
  • Major Histocompatibility Complex / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics