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 (R² = .48%, p empirical = .01, Q = .04) but not the chronicity (R² = .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 (R² = .11%, p empirical = .11, Q = .15), attention-deficit/hyperactivity disorder (R² = .09%, p empirical = .19, Q = .21), or autism spectrum disorder (R² = .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.

Keywords: Attention-deficit/hyperactivity disorder; Autism spectrum disorder; Avon Longitudinal Study of Parents and Children (ALSPAC); Obsessive-compulsive disorder; Polygenic risk score; Tourette syndrome.