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Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci #MMPMID26616563
Martin P; McGovern A; Orozco G; Duffus K; Yarwood A; Schoenfelder S; Cooper NJ; Barton A; Wallace C; Fraser P; Worthington J; Eyre S
Nat Commun 2015[]; 6 (ä): ä PMID26616563show ga
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).