Two of the variants associated with RA in our study, P1104A and I684S, have recently been shown to affect TYK2 function in primary T cells, fibroblasts and B cell lines and impair pro-inflammatory cytokines signalling, providing evidence that both variants are LOF mutations and that LOF mutations in TYK2 alter immune-mediated pathways [33,34]. Here, TYK2 is linked to rheumatoid arthritis.