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.

Figure 1:

Explained variance by the polygenic risk score for each tested phenotype in the Avon Longitudinal Study of Parents and Children (ALSPAC) target sample (7, 8), based on the second Tourette Syndrome genome-wide association study (TS GWAS 2, Yu et al., in prep) as discovery sample. The presence of tics was defined by three different categorizations: “Tics intermediate” (approximating ‘TS/chronic tic disorder (CT) intermediate’ by Scharf et al. (16)), which included individuals that experienced motor and/or vocal tics at least once a week at age 13 years and experienced at least one tic symptom between the ages of 1.5 and 10 years; “Tics broad”, (approximating ‘TS/CT broad’ by Scharf et al. (12)), which included individuals that have experienced motor and/or vocal tics occurring at least once a week at age 13; and “Tics all”, which included individuals that reported at least one positive answer to the tic screening question between the ages 1.5 and 13. The chronicity score is the sum of the number of times tics were present up to age 10.7 plus the number of different tic symptoms at 13.8 years (11,12). The risk scores were calculated at different P-value thresholds (P < 0.0001 with increments of 0.00005 to P < 1) and the model that explained the most variance is reported. * Significance after correction for multiple testing of the different P-value thresholds and for the number of phenotypes tested using the false discovery rate (Q < 0.05).