Genome-wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year.
Methods
We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants.
Results
We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume.
Conclusions
Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Biological Psychiatry |
| ISSN | 0006-3223 |
| DOI | |
| Status | E-pub ahead of print - 2023 |
Bibliografisk note
Funding Information:
This work was supported by EMTICS (FP7-HEALTH, Grant agreement ID No. 278367 [to PP and PJH]), TS-EUROTRAIN (FP7-PEOPLE, Grant agreement ID No. 316978 [to PP]), the National Institute of Neurological Disorders and Stroke (Grant No. R01NS105746), U.S. National Science Foundation (Grant Nos. 2006929 and 1715202 [to PP]), and the National Institute of Mental Health (Grant No. R01MH126213 [to PP]). AJW also received funding from the National Institute of Neurological Disorders and Stroke Grant No. R01NS105746, the Tourette Association of America, and the Weill Institute for Neurosciences. AM received funding from the Deutsche Forschungsgemeinschaft (Grant No. FOR 2698). AS received support from the NIHR UCL/H Biomedical Research Centre. BH is an employee of Boehringer Ingelheim Pharma. CJ received funding from Lundbeck Fonden (Grant No. R100-2011-9332). CB received funding from the Merit-prize fellowship of Semmelweis University, the Bolyai Janos research fellowship of the Hungarian Academy of Sciences (Grant No.BO/00987/16/5), the UNKP-18-4 of the new National Excellence Program of the Ministry of Human Capacities, and the Baron Munchausen Program of the Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University. DCC received funding from the TSAA, the Stichting VC-GGZ, and TS-EUROTRAIN. DM has received research support from Ipsen Corporate and funding grants from Dystonia Medical Research Foundation Canada, Parkinson Canada, The Owerko Foundation, and the Michael P. Smith Family. LKD was supported by grants from the National Institutes of Health (Grant Nos. R01NS102371 and R01NS105746). PM has received grants from the Spanish Ministry of Science and Innovation (Grant No. RTC2019-007150-1), the Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (Grant Nos. PI16/01575, PI19/01576), the Consejeria de Economia, Innovacion, Ciencia y Empleo de la Junta de Andalucia (Grant Nos. CVI-02526, CTS-7685), and the Consejeria de Salud y Bienestar Social de la Junta de Andalucia, (Grant No. PE-0210-2018). PJ and CZ were funded by the National Science Center, Poland (Grant No. UMO-2016/23/B/NZ2/03030). ZT was funded by Lundbeck Fonden (Grant No. R100-2011-9332). TIC Genetics (Tourette International Collaborative Genetics) was supported by the National Institutes of Health (Grant Nos. MH115958, MH115960, MH115962, MH115961, MH115993, MH115963, and MH115959) and the New Jersey Center for Tourette Syndrome and Associated Disorder. Summary statistics data are available upon request to the corresponding authors. The authors report no biomedical financial interests or potential conflicts of interest.
Funding Information:
This work was supported by EMTICS (FP7-HEALTH, Grant agreement ID No. 278367 [to PP and PJH]), TS-EUROTRAIN (FP7-PEOPLE, Grant agreement ID No. 316978 [to PP]), the National Institute of Neurological Disorders and Stroke (Grant No. R01NS105746 ), U.S. National Science Foundation (Grant Nos. 2006929 and 1715202 [to PP]), and the National Institute of Mental Health (Grant No. R01MH12621 3 [to PP]). AJW also received funding from the National Institute of Neurological Disorders and Stroke Grant No. R01NS105746 , the Tourette Association of America, and the Weill Institute for Neurosciences. AM received funding from the Deutsche Forschungsgemeinschaft (Grant No. FOR 2698). AS received support from the NIHR UCL/H Biomedical Research Centre . BH is an employee of Boehringer Ingelheim Pharma. CJ received funding from Lundbeck Fonden (Grant No. R100-2011-9332). CB received funding from the Merit-prize fellowship of Semmelweis University, the Bolyai Janos research fellowship of the Hungarian Academy of Sciences (Grant No.BO/00987/16/5), the UNKP-18-4 of the new National Excellence Program of the Ministry of Human Capacities, and the Baron Munchausen Program of the Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University. DCC received funding from the TSAA, the Stichting VC-GGZ, and TS-EUROTRAIN. DM has received research support from Ipsen Corporate and funding grants from Dystonia Medical Research Foundation Canada , Parkinson Canada , The Owerko Foundation , and the Michael P. Smith Family. LKD was supported by grants from the National Institutes of Health (Grant Nos. R01NS102371 and R01NS105746). PM has received grants from the Spanish Ministry of Science and Innovation (Grant No. RTC2019-007150-1 ), the Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (Grant Nos. PI16/01575, PI19/01576), the Consejeria de Economia, Innovacion, Ciencia y Empleo de la Junta de Andalucia (Grant Nos. CVI-02526, CTS-7685), and the Consejeria de Salud y Bienestar Social de la Junta de Andalucia, (Grant No. PE-0210-2018). PJ and CZ were funded by the National Science Center, Poland (Grant No. UMO-2016/23/B/NZ2/03030). ZT was funded by Lundbeck Fonden (Grant No. R100-2011-9332). TIC Genetics (Tourette International Collaborative Genetics) was supported by the National Institutes of Health (Grant Nos. MH115958 , MH115960 , MH115962 , MH115961 , MH115993 , MH115963 , and MH115959 ) and the New Jersey Center for Tourette Syndrome and Associated Disorder.
Publisher Copyright:
© 2023 Society of Biological Psychiatry
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