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

P Martin, A McGovern, G Orozco, K Duffus… - Nature …, 2015 - nature.com
P Martin, A McGovern, G Orozco, K Duffus, A Yarwood, S Schoenfelder, NJ Cooper
Nature communications, 2015nature.com
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 …
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).
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