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Investigating Shared Genetic Basis Across Tourette Syndrome and Comorbid Neurodevelopmental Disorders Along the Impulsivity-Compulsivity Spectrum
Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
Documents
- 1-s2.0-S000632232100038X-main
Final published version, 1.41 MB, PDF document
DOI
- https://doi.org/10.1016/j.biopsych.2020.12.028
Final published version
- Zhiyu Yang, Purdue University ,
- Hanrui Wu, Purdue University ,
- Phil H Lee, Harvard University ,
- Fotis Tsetsos, Democritus University of Thrace ,
- Lea K Davis, Vanderbilt University ,
- Dongmei Yu, Harvard University ,
- Sang Hong Lee, University of Queensland, University of South Australia ,
- Søren Dalsgaard
- Jan Haavik, University of Bergen ,
- Csaba Barta, Semmelweis University ,
- Tetyana Zayats, Harvard University, University of Bergen ,
- Valsamma Eapen, University of New South Wales ,
- Naomi R Wray, University of Queensland ,
- Bernie Devlin, University of Pittsburgh ,
- Mark Daly, Harvard University, Stanley Center for Psychiatric Research ,
- Benjamin Neale, Harvard University, Stanley Center for Psychiatric Research, Broad Institute ,
- Anders D Børglum
- James J Crowley, University of North Carolina ,
- Jeremiah Scharf, Harvard University ,
- Carol A Mathews, University of Florida ,
- Stephen V Faraone, SUNY Upstate Medical University ,
- Barbara Franke, Radboud University Nijmegen ,
- Manuel Mattheisen, University of Würzburg, Karolinska Institutet ,
- Jordan W Smoller, Harvard University, Stanley Center for Psychiatric Research ,
- Peristera Paschou, Purdue University
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.
| Original language | English |
|---|---|
| Journal | Biological Psychiatry |
| Volume | 90 |
| Issue | 5 |
| Pages (from-to) | 317-327 |
| Number of pages | 11 |
| ISSN | 0006-3223 |
| DOIs | |
| Publication status | Published - Sept 2021 |
- ADHD, ASD, Cross-disorder genetic analysis, GWAS meta-analysis, OCD, Tourette syndrome
Research areas
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