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 that have accompanied the coronavirus disease-19 (COVID-19) pandemic, the clinical presentation of the syndrome varies greatly from one individual to another. Potential host factors that accompany greater risk from COVID-19 have been sought and schizophrenia (SCZ) patients seem to present more severe COVID-19 than control counterparts, with certain gene expression similarities between psychiatric and COVID-19 patients reported. We used summary statistics from the last SCZ, bipolar disorder (BD), and depression (DEP) meta-analyses available on the Psychiatric Genomics Consortium webpage to calculate polygenic risk scores (PRSs) for a target sample of 11,977 COVID-19 cases and 5943 subjects with unknown COVID-19 status. Linkage disequilibrium score (LDSC) regression analysis was performed when positive associations were obtained from the PRS analysis. The SCZ PRS was a significant predictor in the case/control, symptomatic/asymptomatic, and hospitalization/no hospitalization analyses in the total and female samples; and of symptomatic/asymptomatic status in men. No significant associations were found for the BD or DEP PRS or in the LDSC regression analysis. SNP-based genetic risk for SCZ, but not for BD or DEP, may be associated with higher risk of SARS-CoV-2 infection and COVID-19 severity, especially among women; however, predictive accuracy barely exceeded chance level. We believe that the inclusion of sexual loci and rare variations in the analysis of genomic overlap between SCZ and COVID-19 will help to elucidate the genetic commonalities between these conditionsThis study has been funded by Instituto de Salud Carlos III (COV20_00622 to AC) and cofunded by European Union (ERDF) “A way of making Europe”, Fundación Amancio Ortega, Banco de Santander (to AC). The contribution of the Centro National de Genotipado (CEGEN), and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures, is also acknowledged. Authors are also particularly grateful to Banco Nacional de ADN and GRA@CE cohort group. MA was supported by a Juan de la Cierva contract (FJC2021-047538-I)