In conclusion, although previous studies have nominated TYK2 as a potential therapeutic target [41,65], our study provides compelling human genetic data demonstrating that TYK2 alleles with partial loss-of-function (1) protect against RA, SLE and potentially other autoimmune diseases such as IBD; and (2) are tolerated in the general population, as there are no obvious detrimental associations in our PheWAS. This evidence concerns the gene TYK2 and autoimmune disease.