Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci.
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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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2041-1723
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Wellcome Trust (100140/Z/12/Z)
European Commission (241447)
Wellcome Trust (091157/Z/10/B)
Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0405)
Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0404)