Polygenic Risk Scores Derived From a Tourette Syndrome Genome-wide Association Study Predict Presence of Tics in the Avon Longitudinal Study of Parents and Children Cohort.

Abstract Background Tourette syndrome (TS) has a well-established genetic background, but its genetic architecture remains largely unknown. The authors investigated the role of polygenic risk scores (PRSs) derived from a TS genome-wide association study in relation to the occurrence of tics and associated traits in a general population cohort. Methods Using the most recent TS genome-wide association study (n = 4819 cases; n = 9488 controls) as the discovery sample, PRSs were calculated in Avon Longitudinal Study of Parents and Children participants (n = 8941). Regression analyses were used to assess whether PRS predicted the presence and chronicity of tics, and symptom severity of obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and autism spectrum disorder in Avon Longitudinal Study of Parents and Children participants. Results Following correction for multiple testing, the PRS significantly predicted the presence (R 2 =.48%, p empirical =.01, Q =.04) but not the chronicity (R 2 =.16%, p empirical =.07 , Q =.14) of tics in the Avon Longitudinal Study of Parents and Children cohort; it did not predict the severity of obsessive-compulsive disorder (R 2 =.11%, p empirical =.11, Q =.15), attention-deficit/hyperactivity disorder (R 2 =.09%, p empirical =.19, Q =.21), or autism spectrum disorder (R 2 =.12%, p empirical =.09, Q =.14). Conclusions The authors found a significant polygenic component of tics occurring in a general population cohort based on PRS derived from a genome-wide association study of individuals with a TS diagnosis. This finding supports the notion that tics along a spectrum from nonclinical to clinical symptom levels share a similar genetic background. [ABSTRACT FROM AUTHOR]