Taehyeung Kim, Marta Martínez-Bonet, Qiang Wang, Nicolaj Hackert, Jeffrey A Sparks, Yuriy Baglaenko, Byunghee Koh, Roxane Darbousset, Raquel Laza-Briviesca, Xiaoting Chen, Vitor R C Aguiar, Darren J Chiu, Harm-Jan Westra, Maria Gutierrez-Arcelus, Matthew T Weirauch, Soumya Raychaudhuri, Deepak A Rao, Peter A Nigrovic
Fine-mapping and functional studies implicate rs117701653, a non-coding single nucleotide polymorphism in the CD28/CTLA4/ICOS locus, as a risk variant for rheumatoid arthritis and type 1 diabetes. Here, using DNA pulldown, mass spectrometry, genome editing and eQTL analysis, we establish that the disease-associated risk allele is functional, reducing affinity for the inhibitory chromosomal regulator SMCHD1 to enhance expression of inducible T-cell costimulator (ICOS) in memory CD4+ T cells from healthy donors...
March 9, 2024: Nature Communications