TYK2 and connective tissue disorder: We observed Cystatin C mediated the association of TYK2 mutations with hypothyroidism (P for ACME <0.001), rheumatoid arthritis (P for ACME = 0.02), ulcerative colitis (P for ACME = 0.02), chronic hepatitis (P for ACME <0.001), type 1 diabetes (P for ACME <0.001), Celiac disease (P for ACME <0.001), and diffuse diseases of connective tissue (P for ACME <0.001).