Joint evaluation of serum C-Reactive Protein levels and polygenic risk scores as risk factors for schizophrenia

Several studies have indicated infectious and immune-related abnormalities in schizophrenia (Scz), including elevated serum C-reactive protein (CRP)-a well-known proxy for infections/immune abnormalities. A portion of the genetic risk for Scz can be estimated using the polygenic risk score (PGRS). It is not known whether there is an interaction in the risks traceable to CRP and PGRS. Patients with Scz and individuals without psychosis were evaluated systematically using DSM IV criteria (N=794, N = 446, respectively). To estimate risk for Scz attributable to CRP and PGRS, serum from these participants was assayed for CRP levels using enzyme linked immunosorbent assays. PGRS was estimated from common DNA polymorphisms associated with Scz from genome wide association studies. CRP level and PGRS were not significantly correlated. Using a generalized linear logistic model, case/control status was evaluated in relation to the following predictors: CRP, PGRS, and demographic variables. CRP and PGRS were individually associated with case status; CRP: odds ratio (OR) 1.27, 95% confidence intervals (95% Cl) 1.12, 1.43; p = 0.0001; PGRS: OR 1.66, 95% CI 1.47, 1.89; p = 1.28 x 10-15. There were no significant interactions between PGRS and CRP for predicting Scz versus control status.