TY - JOUR T1 - Chromosome contacts in activated T cells identify autoimmune disease-candidate genes JF - bioRxiv DO - 10.1101/100958 SP - 100958 AU - Oliver S Burren AU - Arcadio Rubio GarcĂ­a AU - Biola-Maria Javierre AU - Daniel B Rainbow AU - Jonathan Cairns AU - Nicholas J Cooper AU - John J Lambourne AU - Ellen Schofield AU - Xaquin Castro Dopico AU - Ricardo C Ferreira AU - Richard Coulson AU - Frances Burden AU - Sophia P Rowlston AU - Kate Downes AU - Steven W Wingett AU - Mattia Frontini AU - Willem H Ouwehand AU - Peter Fraser AU - Mikhail Spivakov AU - John A Todd AU - Linda S Wicker AU - Antony J Cutler AU - Chris Wallace Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/08/04/100958.abstract N2 - Background Autoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4+ T cells. Linking such regulatory regions to gene promoters in disease relevant cell contexts facilitates identification of candidate disease genes.Results Within four hours, activation of CD4+ T cells invokes changes in histone modifications and enhancer RNA transcription that correspond to altered expression of the interacting genes identified by promoter capture Hi-C (PCHi-C). By integrating PCHi-C data with genetic associations for five autoimmune diseases we prioritised 245 candidate genes with a median distance from peak signal to prioritised gene of 153 kb. Just under half (108/245) prioritised genes related to activation-sensitive interactions. This included IL2RA, where allele-specific expression analyses were consistent with its interaction-mediated regulation, illustrating the utility of the approach.Conclusions Our systematic experimental framework offers an alternative approach to candidate causal gene identification for variants with cell state-specific functional effects, with achievable sample sizes. ER -