With the exception of tyrosine kinase-2 (Tyk2), in which a rare single nucleotide polymorphism in a well conserved APE motif within the pseudokinase domain is fully penetrant in controlling susceptibility to autoimmune diseases [29], [30], the vast majority of non-MHC autoimmune loci identified to date are QTL that exhibit only partial to minimal penetrance. Here, TYK2 is linked to autoimmune disease.