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 |
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Authors: | Mohamed Abdulkadir Carol A Mathews Jeremiah M Scharf Dongmei Yu Jay A Tischfield Gary A Heiman Pieter J Hoekstra Andrea Dietrich |
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Institution: | 1. Department of Genetics, Rutgers, the State University of New Jersey, and the Human Genetics Institute of New Jersey, Piscataway, New Jersey;2. Department of Child and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;3. Department of Psychiatry, Center for OCD, Anxiety and Related Disorders, and Genetics Institute, University of Florida College of Medicine, Gainesville, Florida;4. Center for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;5. Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts |
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Abstract: | BackgroundTourette 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.MethodsUsing 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.ResultsFollowing 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).ConclusionsThe 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. |
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Keywords: | Attention-deficit/hyperactivity disorder Autism spectrum disorder Avon Longitudinal Study of Parents and Children (ALSPAC) Obsessive-compulsive disorder Polygenic risk score Tourette syndrome |
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