Abstract
Original language | English |
---|---|
Number of pages | 11 |
Journal | Biological Psychiatry |
Early online date | 2 Feb 2023 |
DOIs | |
Publication status | Published - Feb 2023 |
Keywords
- GWAS
- Meta-analysis
- NR2F1
- Tourette syndrome
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In: Biological Psychiatry, 02.2023.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Genome-wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome
AU - The TIC Genetics Collaborative Group
AU - The TSGeneSEE Initiative
AU - the EMTICS Collaborative Group
AU - The TS-EUROTRAIN Network
AU - The PGC TS Working Group
AU - Tsetsos, Fotis
AU - Topaloudi, Apostolia
AU - Jain, Pritesh
AU - Yang, Zhiyu
AU - Yu, Dongmei
AU - Kolovos, Petros
AU - Tumer, Zeynep
AU - Rizzo, Renata
AU - Hartmann, Andreas
AU - Depienne, Christel
AU - Worbe, Yulia
AU - Müller-Vahl, Kirsten R.
AU - Cath, Danielle C.
AU - Boomsma, Dorret I.
AU - Wolanczyk, Tomasz
AU - Zekanowski, Cezary
AU - Barta, Csaba
AU - Nemoda, Zsofia
AU - Tarnok, Zsanett
AU - Padmanabhuni, Shanmukha S.
AU - Buxbaum, Joseph D.
AU - Grice, Dorothy
AU - Glennon, Jeffrey
AU - Stefansson, Hreinn
AU - Hengerer, Bastian
AU - Yannaki, Evangelia
AU - Stamatoyannopoulos, John A.
AU - Benaroya-Milshtein, Noa
AU - Cardona, Francesco
AU - Hedderly, Tammy
AU - Heyman, Isobel
AU - Huyser, Chaim
AU - Mir, Pablo
AU - Morer, Astrid
AU - Mueller, Norbert
AU - Munchau, Alexander
AU - Plessen, Kerstin J.
AU - Porcelli, Cesare
AU - Roessner, Veit
AU - Walitza, Susanne
AU - Schrag, Anette
AU - Martino, Davide
AU - Barr, Cathy L.
AU - The TSAICG
AU - Batterson, James R.
AU - Berlin, Cheston
AU - Budman, Cathy L.
AU - Coppola, Giovanni
AU - Cox, Nancy J.
AU - Darrow, Sabrina
AU - Dion, Yves
AU - Tourette Syndrome Association International Consortium for Genetics (TSAICG)
AU - Tischfield, Jay A.
AU - Heiman, Gary A.
AU - Willsey, A. Jeremy
AU - Dietrich, Andrea
AU - Davis, Lea K.
AU - Crowley, James J.
AU - Mathews, Carol A.
AU - Scharf, Jeremiah M.
AU - Smit, Jan H.
AU - Driessen, Nicole
AU - Fan, Siyan
AU - van den Heuvel, Odile A.
AU - Pouwels, Petra J. W.
AU - Veltman, Dick J.
AU - van der Werf, Ysbrand D.
N1 - 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
PY - 2023/2
Y1 - 2023/2
N2 - Background: 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.
AB - Background: 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.
KW - GWAS
KW - Meta-analysis
KW - NR2F1
KW - Tourette syndrome
UR - http://www.scopus.com/inward/record.url?scp=85151260500&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85151260500&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/36738982
U2 - 10.1016/j.biopsych.2023.01.023
DO - 10.1016/j.biopsych.2023.01.023
M3 - Article
C2 - 36738982
SN - 0006-3223
JO - Biological Psychiatry
JF - Biological Psychiatry
ER -