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

2015; Nature Portfolio; Volume: 6; Issue: 1 Linguagem: Inglês

10.1038/ncomms10069

2041-1723

Paul Martin, Amanda McGovern, Gisela Orozco, Kate Duffus, Annie Yarwood, Stefan Schoenfelder, Nicholas Cooper, Anne Barton, Chris Wallace, Peter Fraser, Jane Worthington, Stephen Eyre,

Genomics and Chromatin Dynamics

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) .