Four other genes identified through these analyses are located in the MHC locus, a region on chromosome 6 that has a major role in the adaptive immune system and has been repeatedly linked to major psychiatric disorders61. The newly identified MHC association for OCD is noteworthy given evidence linking OCD with autoimmune disorders62–64. Genetic pleiotropy may underlie this connection, with variants predisposing individuals to both autoimmune conditions and OCD65. Furthermore, some OCD subtypes, such as pediatric acute-onset neuropsychiatric disorders associated with Streptococcus and pediatric acute-onset neuropsychiatric syndrome, may have autoimmune origins66,67. Nevertheless, we were surprised to discover several negative genetic correlations between OCD and autoimmune disorders such as Crohn’s disease, ulcerative colitis and inflammatory bowel disease in our analyses, suggesting that there is heterogeneity (and perhaps pleiotropy) in the genetic relationships between autoimmune disorders and OCD.
