Investigating Shared Genetic Basis Across Tourette Syndrome and Comorbid Neurodevelopmental Disorders Along the Impulsivity-Compulsivity Spectrum
Year: 2021
Type: review
Abstract: BACKGROUND: Tourette syndrome (TS) is often found comorbid with other neurodevelopmental disorders across the impulsivity-compulsivity spectrum, with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) as most prevalent. This points to the possibility of a common etiological thread along an impulsivity-compulsivity continuum. METHODS: Investigating the shared genetic basis across TS, ADHD, ASD, and OCD, we undertook an evaluation of cross-disorder genetic architecture and systematic meta-analysis, integrating summary statistics from the latest genome-wide association studies (93,294 individuals, 6,788,510 markers). RESULTS: As previously identified, a common unifying factor connects TS, ADHD, and ASD, while TS and OCD show the highest genetic correlation in pairwise testing among these disorders. Thanks to a more homogeneous set of disorders and a targeted approach that is guided by genetic correlations, we were able to identify multiple novel hits and regions that seem to play a pleiotropic role for the specific disorders analyzed here and could not be identified through previous studies. In the TS-ADHD-ASD genome-wide association study single nucleotide polymorphism-based and gene-based meta-analysis, we uncovered 13 genome-wide significant regions that host single nucleotide polymorphisms with a high posterior probability for association with all three studied disorders (m-value > 0.9), 11 of which were not identified in previous cross-disorder analysis. In contrast, we also identified two additional pleiotropic regions in the TS-OCD meta-analysis. Through conditional analysis, we highlighted genes and genetic regions that play a specific role in a TS-ADHD-ASD genetic factor versus TS-OCD. Cross-disorder tissue specificity analysis implicated the hypothalamus-pituitary-adrenal gland axis in TS-ADHD-ASD. CONCLUSIONS: Our work underlines the value of redefining the framework for research across traditional diagnostic categories.
Source: Biological Psychiatry
Authors: Zhiyu Yang, Hanrui Wu, Phil H. Lee, Fotis Tsetsos, Lea K. Davis, Dongmei Yu, Sang Hong Lee, Søren Dalsgaard, Jan Haavik, Csaba Barta, Tetyana Zayats, Valsamma Eapen, Naomi R. Wray, Bernie Devlin, Mark Daly, Benjamin Neale, Anders D. Børglum, James J. Crowley, Jeremiah Scharf, Carol A. Mathews, Stephen V. Faraone, Barbara Franke, Manuel Mattheisen, Jordan W. Smoller, Peristera Paschou
Institutions: Purdue University West Lafayette, Harvard University, Massachusetts General Hospital, Democritus University of Thrace, Vanderbilt University, Vanderbilt University Medical Center, The University of Queensland, University of South Australia, Aarhus University, Telemark Hospital, Lundbeck Foundation, Haukeland University Hospital, University of Bergen, Semmelweis University, UNSW Sydney, Institute for Molecular Bioscience, University of Pittsburgh, Broad Institute, Stanley Center for Psychiatric Research, University of North Carolina at Chapel Hill, University of Florida Health, University of Florida, SUNY Upstate Medical University, Radboud University Nijmegen, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Karolinska Institutet, Universitätsklinikum Würzburg
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: hybrid
Estimated APC paid: $3,990
Funders: National Science Foundation, Cancer Research Institute, Massachusetts General Hospital, Purdue University, Vanderbilt University, International OCD Foundation, Syracuse University, State University of New York, Aarhus Universitet, University of Pittsburgh, Sunovion, Chiropractic and Osteopathic College of Australasia, Vanderbilt University Medical Center, Broad Institute, University of New South Wales, University of South Australia, Radboud Universiteit, Semmelweis Egyetem, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Lundbeckfonden, Karolinska Institutet, Universitetet i Bergen, Radboud Universitair Medisch Centrum, Trakya Üniversitesi, Novo Nordisk Fonden, Haukeland Universitetssjukehus, National Institutes of Health, Directorate for Biological Sciences, University of North Carolina at Chapel Hill, Horizon 2020 Framework Programme, State University of New York Upstate Medical University, Seventh Framework Programme, Stanley Center for Psychiatric Research, Broad Institute, Queensland Brain Institute, Horizon 2020, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Integrating Common and Rare Variation to Discover Genes Associated with Tourette Syndrome, G214445032, G2383258991, Advancing Tourette Syndrome genetics using bioinformatics and genome biology, Comprehensive analysis of genetic pleiotropy in eleven neuropsychiatric disorders, G3987400284, G408622963, 3/7 Psychiatric Genomics Consortium: Finding actionable variation, Overall: Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at Vanderbilt, Longitudinal Family/Molecular Genetic Study to Validate Research Domain Criteria, Large-Scale Collaborative Genetic and Epigenetic Studies of Tourette Syndrome, G7080166265, Genetic & Environmental Predictors of Tourette Syndrome & OCD in Denmark, G8341330702, III: Small: Novel Statistical Data Analysis Approaches for Mining Human Genetics Datasets
OpenAlex ID: W3118854417