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Inflammatory markers have been associated with schizophrenia, but the direction of the association has not been clear. To address this question, Brazilian investigators used two-sample Mendelian randomization (MR) drawing on published data on genetic variants for C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1Ra), and soluble interleukin-6 receptor (sIL-6R) as proxies for the total genetic “dose” for these markers.
The validity of these proxies was established in large genome-wide association studies, and gene–schizophrenia associations were established in studies from 30,000 patients and 45,000 controls. The analysis demonstrated that elevations of CRP inferred from the combination of inherited alleles reduced schizophreni…