Investigating Shared Genetic Basis Across Tourette Syndrome and Comorbid Neurodevelopmental Disorders Along the Impulsivity-Compulsivity Spectrum
dc.contributor.author | Yang, Zhiyu | |
dc.contributor.author | Wu, Hanrui | |
dc.contributor.author | Lee, Phil H. | |
dc.contributor.author | Tsetsos, Fotis | |
dc.contributor.author | Davis, Lea K. | |
dc.contributor.author | Yu, Dongmei | |
dc.contributor.author | Lee, Sang Hong | |
dc.contributor.author | Dalsgaard, Søren | |
dc.contributor.author | Haavik, Jan | |
dc.contributor.author | Barta, Csaba | |
dc.contributor.author | Zayats, Tetyana | |
dc.contributor.author | Eapen, Valsamma | |
dc.contributor.author | Wray, Naomi R. | |
dc.contributor.author | Devlin, Bernie | |
dc.contributor.author | Daly, Mark | |
dc.contributor.author | Neale, Benjamin | |
dc.contributor.author | Børglum, Anders D. | |
dc.contributor.author | Crowley, James J. | |
dc.contributor.author | Scharf, Jeremiah | |
dc.contributor.author | Mathews, Carol A. | |
dc.contributor.author | Faraone, Stephen V. | |
dc.contributor.author | Franke, Barbara | |
dc.contributor.author | Mattheisen, Manuel | |
dc.contributor.author | Smoller, Jordan W. | |
dc.contributor.author | Paschou, Peristera | |
dc.date.accessioned | 2022-04-04T13:19:18Z | |
dc.date.available | 2022-04-04T13:19:18Z | |
dc.date.created | 2021-04-19T09:03:52Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 0006-3223 | |
dc.identifier.uri | https://hdl.handle.net/11250/2989693 | |
dc.description.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. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/deed.no | * |
dc.title | Investigating Shared Genetic Basis Across Tourette Syndrome and Comorbid Neurodevelopmental Disorders Along the Impulsivity-Compulsivity Spectrum | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.doi | 10.1016/j.biopsych.2020.12.028 | |
dc.identifier.cristin | 1904976 | |
dc.source.journal | Biological Psychiatry | en_US |
dc.source.pagenumber | 317-327 | en_US |
dc.identifier.citation | Biological Psychiatry. 2021, 90 (5), 317-327. | en_US |
dc.source.volume | 90 | en_US |
dc.source.issue | 5 | en_US |
Files in this item
This item appears in the following Collection(s)
-
Department of Biomedicine [739]
-
Registrations from Cristin [10237]