Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci

Nat Commun. 2015 Nov 30:6:10069. doi: 10.1038/ncomms10069.

Abstract

Genome-wide association studies have been tremendously successful in identifying genetic variants associated with complex diseases. The majority of association signals are intergenic and evidence is accumulating that a high proportion of signals lie in enhancer regions. We use Capture Hi-C to investigate, for the first time, the interactions between associated variants for four autoimmune diseases and their functional targets in B- and T-cell lines. Here we report numerous looping interactions and provide evidence that only a minority of interactions are common to both B- and T-cell lines, suggesting interactions may be highly cell-type specific; some disease-associated SNPs do not interact with the nearest gene but with more compelling candidate genes (for example, FOXO1, AZI2) often situated several megabases away; and finally, regions associated with different autoimmune diseases interact with each other and the same promoter suggesting common autoimmune gene targets (for example, PTPRC, DEXI and ZFP36L1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / metabolism
  • B-Lymphocytes / metabolism
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study / methods*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • T-Lymphocytes / metabolism