Structured AbstractImportanceTics are a common feature of early-onset neurodevelopmental disorders, characterized by involuntary and repetitive movements or sounds. Despite affecting up to 2% of young children and having a genetic contribution, the underlying causes remain poorly understood, likely due to the complex phenotypic and genetic heterogeneity among affected individuals.ObjectiveIn this study, we leverage dense phenotype information from electronic health records to identify the disease features associated with tic disorders within the context of a clinical biobank. These disease features are then used to generate a phenotype risk score for tic disorder.DesignUsing de-identified electronic health records from a tertiary care center, we extracted individuals with tic disorder diagnosis codes. We performed a phenome-wide association study to identify the features enriched in tic cases versus controls (N=1,406 and 7,030; respectively). These disease features were then used to generate a phenotype risk score for tic disorder, which was applied across an independent set of 90,051 individuals. A previously curated set of tic disorder cases from an electronic health record algorithm followed by clinician chart review was used to validate the tic disorder phenotype risk score.Main Outcomes and MeasuresPhenotypic patterns associated with a tic disorder diagnosis in the electronic health record.ResultsOur tic disorder phenome-wide association study revealed 69 significantly associated phenotypes, predominantly neuropsychiatric conditions, including obsessive compulsive disorder, attention-deficit hyperactivity disorder, autism, and anxiety. The phenotype risk score constructed from these 69 phenotypes in an independent population was significantly higher among clinician-validated tic cases versus non-cases.Conclusions and RelevanceOur findings provide support for the use of large-scale medical databases to better understand phenotypically complex diseases, such as tic disorders. The tic disorder phenotype risk score provides a quantitative measure of disease risk that can be leveraged for the assignment of individuals in case-control studies or for additional downstream analyses.Key PointsQuestionCan clinical features within the electronic medical records of patients with tic disorders be used to generate a quantitative risk score that can identify other individuals at high probability of tic disorders?FindingsIn this phenome-wide association study using data from electronic health records, we identify the medical phenotypes associated with a tic disorder diagnosis. We then use the resulting 69 significantly associated phenotypes, which include several neuropsychiatric comorbidities, to generate a tic disorder phenotype risk score in an independent population and validate this score with clinician-validated tic cases.MeaningThe tic disorder phenotype risk score provides a computational method of evaluating and distilling the comorbidity patterns that characterize tic disorders (independent of tic diagnosis status) and may help improve downstream analyses by distinguishing between individuals that should be categorized as cases or controls for tic disorder population studies.