Deep sequencing of the MHC region in the Chinese population contributes to studies of complex disease

Nat Genet. 2016 Jul;48(7):740-6. doi: 10.1038/ng.3576. Epub 2016 May 23.

Abstract

The human major histocompatibility complex (MHC) region has been shown to be associated with numerous diseases. However, it remains a challenge to pinpoint the causal variants for these associations because of the extreme complexity of the region. We thus sequenced the entire 5-Mb MHC region in 20,635 individuals of Han Chinese ancestry (10,689 controls and 9,946 patients with psoriasis) and constructed a Han-MHC database that includes both variants and HLA gene typing results of high accuracy. We further identified multiple independent new susceptibility loci in HLA-C, HLA-B, HLA-DPB1 and BTNL2 and an intergenic variant, rs118179173, associated with psoriasis and confirmed the well-established risk allele HLA-C*06:02. We anticipate that our Han-MHC reference panel built by deep sequencing of a large number of samples will serve as a useful tool for investigating the role of the MHC region in a variety of diseases and thus advance understanding of the pathogenesis of these disorders.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian Continental Ancestry Group / genetics*
  • Butyrophilins / genetics
  • Case-Control Studies
  • China / epidemiology
  • Genetic Predisposition to Disease
  • HLA-B Antigens / genetics
  • HLA-C Antigens / genetics
  • HLA-DP beta-Chains / genetics
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Major Histocompatibility Complex / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Psoriasis / epidemiology
  • Psoriasis / genetics*

Substances

  • BTNL2 protein, human
  • Butyrophilins
  • HLA-B Antigens
  • HLA-C Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen