Developing a phenotype risk score for tic disorders in a large, clinical biobank
Year: 2024
Type: article
Study design: Observational Study
Abstract: Tics are a common feature of early-onset neurodevelopmental disorders, characterized by involuntary and repetitive movements or sounds. Despite affecting up to 2% of children and having a genetic contribution, the underlying causes remain poorly understood. In this study, we leverage dense phenotype information to identify features (i.e., symptoms and comorbid diagnoses) of tic disorders within the context of a clinical biobank. Using de-identified electronic health records (EHRs), we identified individuals with tic disorder diagnosis codes. We performed a phenome-wide association study (PheWAS) to identify the EHR features enriched in tic cases versus controls ( n = 1406 and 7030; respectively) and found highly comorbid neuropsychiatric phenotypes, including: obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, and anxiety ( p < 7.396 × 10 −5 ). These features (among others) were then used to generate a phenotype risk score (PheRS) for tic disorder, which was applied across an independent set of 90,051 individuals. A gold standard set of tic disorder cases identified by an EHR algorithm and confirmed by clinician chart review was then used to validate the tic disorder PheRS; the tic disorder PheRS was significantly higher among clinician-validated tic cases versus non-cases ( p = 4.787 × 10 −151 ; β = 1.68; SE = 0.06). Our findings provide support for the use of large-scale medical databases to better understand phenotypically complex and underdiagnosed conditions, such as tic disorders.
Source: Translational Psychiatry
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: gold
Estimated APC paid: $4,990
Funders: U.S. Department of Health and Human Services, Vanderbilt University, Tourette Association of America, Vanderbilt University Medical Center, Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1435936284, Pharmacogenomics of Arrhythmia Therapy, G1531600799, Integrating Common and Rare Variation to Discover Genes Associated with Tourette Syndrome, G1766209448, G1846282300, G2103760183, Understanding the genetic risk underlying racial disparities in uterine fibroids, G2615776415, G2683268942, G3047920937, Improving Prediction of Drug Action, G3395468139, G3619590958, G364208108, G3791753988, G3938985443, G4049315607, G4198746417, Automated Storage and Retrieval of Biological Systems, G4395870004, G4410787187, Overall: Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at Vanderbilt, G5016112840, BioVU Plasma Storage Equipment, G560889077, G5679716143, G5717004637, G5905461776, Genetic Epidemiology of Multiple Sclerosis, G6173849340, G6589054092, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, Large-Scale Collaborative Genetic and Epigenetic Studies of Tourette Syndrome, G6851591967, VESPA: Vanderbilt Electronic Systems for Pharmacogenomic Assessment, G7163342664, G7525431604, The Vanderbilt Institute for Clinical and Translational Research (VICTR), Vanderbilt Genome Electronic Records Project, G8025844438, G8098630230, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), G8332127685, Vanderbilt Institute for Clinical and Translational Research (VICTR), Neurophysiologic Correlates of Sensory Over-Responsivity in Tourette Syndrome, Institutional Career Development Core, VGM: Vanderbilt Genomic Medicine Training Program
OpenAlex ID: W4401062749