The use of polygenic risk scores as a covariate in psychological studies

Abstract

Polygenic risk scores (PRS) are increasingly used to predict diseases (e.g., schizophrenia). However, the proper application of the PRS in psychological studies is sparse. We aimed to evaluate the methodological aspects of using PRS as a covariate in causal association studies in psychology. We conducted a simulation study using realistic scenarios, such as gene and exposure or confounder interaction, gene and gene interaction, gene acts as confounding and instrumental variable and replicated each scenario 1000 times. We found that when the genotype(s) that was used for calculating PRS interacted with the exposure and if the analyses considering this interaction, the exposure effect similar with the true value. However, a significant amount of bias was present even after adjustment for the measured confounders i) when the gene interacted with the unmeasured confounder and this bias amplified when the interaction effect was two times stronger; and ii) when the gene acts as a confounder or instrumental variable. Therefore, theoretical knowledge of psychology should be incorporated when the PRS is utilized in psychological causal association studies in order to reduce systematic bias and improve the precision of the exposure effect.