Psychiatric polygenic risk as a predictor of COVID-19 risk and severity: insight into the genetic overlap between schizophrenia and COVID-19

Despite the high contagion and mortality rates during the COVID-19 pandemic, clinical presentation varies greatly among individuals. Schizophrenia (SCZ) patients appear to experience more severe COVID-19 than controls, and certain gene expression similarities between psychiatric and COVID-19 patients have been reported. Using summary statistics from the latest SCZ, bipolar disorder (BD), and depression (DEP) meta-analyses from the Psychiatric Genomics Consortium, polygenic risk scores (PRSs) were calculated for a target sample of 11,977 COVID-19 cases and 5943 subjects with unknown COVID-19 status. Linkage disequilibrium score (LDSC) regression was performed when positive PRS associations were obtained. The SCZ PRS significantly predicted case/control, symptomatic/asymptomatic, and hospitalization/no hospitalization outcomes in the total and female samples, and symptomatic/asymptomatic status in men. No significant associations were found for BD or DEP PRS or in LDSC regression. SNP-based genetic risk for SCZ may be associated with higher risk of SARS-CoV-2 infection and COVID-19 severity, especially among women; however, predictive accuracy barely exceeded chance. Including sex chromosome loci and rare variation in analyses of genomic overlap between SCZ and COVID-19 may help elucidate shared genetic factors.