Polygenic and environmental determinants of tics in the Avon Longitudinal Study of Parents and Children cohort

ABSTRACT BACKGROUND Tourette syndrome (TS) is caused by multiple genetic and environmental factors. Yet, little is known about the interplay of these factors in the occurrence of tics in the general population. METHODS Using logistic regression, we investigated whether polygenic risk score (PRS) of TS and pregnancy-related environmental factors together enhance the explained variance of tic occurrence (as opposed to separate analysis) in the Avon Longitudinal Study of Parents and Children. We included a cumulative adverse pregnancy risk score, maternal anxiety and depression, and maternal smoking and alcohol use during pregnancy. We investigated possible independent (i.e. additive) genetic and environmental effects, gene-environment correlations ( r GE), gene-environment interactions (G x E), and mediation effects in explaining tic presence. RESULTS Models that contained the PRS and the cumulative adverse pregnancy risk score, maternal anxiety, or maternal depression (but not maternal smoking and alcohol use) explained significantly more variance of tic presence compared to models including only the PRS, pointing to additive effects. Furthermore, we found that maternal anxiety, depression, and smoking were mediated by the cumulative adverse pregnancy risk score, and were thus all indirectly associated with tics through pregnancy complications. We did not find r GE or G x E. CONCLUSIONS We found evidence for both direct and indirect associations of environmental risk factors in relation to tics in the general population. Combining PRS and environmental risk factors improve our understanding of tics compared to considering these factors in isolation, suggesting both additive and mediation effects.