Several lines of evidence implicate immune abnormalities in the pathophysiology of
severe mental disorders (SMD) and comorbid
mental disorders. Here, we use the data from genome-wide association studies (GWAS) of
autoimmune diseases and mental phenotypes associated with SMD to disentangle
genetic susceptibilities of immune abnormalities in SMD. We included 1004 patients with SMD and 947 healthy controls (HC) and measured plasma levels of
IL-1Ra, sIL-2R, gp130, sTNFR-1,
IL-18, APRIL, and
ICAM-1.
Polygenic risk scores (PRS) of six autoimmune disorders, CRP, and 10 SMD-related mental phenotypes were calculated from GWAS. General linear models were applied to assess the association of PRS with
immune marker abnormalities. We found negative associations between PRS of educational attainment and
IL-1Ra (P = 0.01) and
IL-18 (P = 0.01). There were nominal positive associations between PRS of
psoriasis and
sgp130 (P = 0.02) and PRS of anxiety and
IL-18 (P = 0.03), and nominal negative associations between PRS of anxiety and sIL-2R (P = 0.02) and PRS of educational attainment and sIL-2R (P = 0.03). Associations explained minor amounts of the
immune marker plasma-level difference between SMD and HC. Different PRS and
immune marker associations in the SMD group compared to HC were shown for PRS of extraversion and
IL-1Ra ([interaction effect (IE), P = 0.002), and nominally for PRS of openness and
IL-1Ra (IE, P = 0.02) and sTNFR-1 (IE, P = 0.04). Our findings indicate polygenic susceptibilities to immune abnormalities in SMD involving genetic overlap with SMD-related mental phenotypes and
psoriasis. Associations might suggest immune genetic factors of SMD subgroups characterized by autoimmune or specific mental features.