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.
Genome-wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome / Tsetsos, F; Topaloudi, A; Jain, P; Yang, Z; Yu, D; Kolovos, P; Tumer, Z; Rizzo, R; Hartmann, A; Depienne, C; Worbe, Y; Müller-Vahl, Kr; Cath, Dc; Boomsma, Di; Wolanczyk, T; Zekanowski, C; Barta, C; Nemoda, Z; Tarnok, Z; Padmanabhuni, Ss; Buxbaum, Jd; Grice, D; Glennon, J; Stefansson, H; Hengerer, B; Yannaki, E; Stamatoyannopoulos, Ja; Benaroya-Milshtein, N; Cardona, F; Hedderly, T; Heyman, I; Huyser, C; Mir, P; Morer, A; Mueller, N; Munchau, A; Plessen, Kj; Porcelli, C; Roessner, V; Walitza, S; Schrag, A; Martino, D; Openneer, ha€ıra J. C.; Chaim, Huyser; Martino, Davide; Anette, Schrag; Alan, Apter; Baglioni, Valentina; Juliane, Ball; Noa, Benaroya-Milshtein; Emese, Bognar; Bianka, Burger; Judith, Buse; Francesco, Cardona; Marta Correa Vela, ; Nanette, M Debes; Andrea, Dietrich; Maria Cristina Ferro, ; Carolin, Fremer; Blanca, Garcia-Delgar; Mariangela, Gulisano; Annelieke, Hagen; Julie, Hagstrøm; Tammy, J Hedderly; Isobel, Heyman; Chaim, Huyser; Marcos, Madruga-Garrido; Pablo, Mir; Norbert, Müller; Peter, Nagy; Neri, Valeria; Thaïra J, C Openneer; Pellico, Alessandra; Kerstin, J Plessen; Cesare, Porcelli; Renata, Rizzo; Daphna, Ruhrman; Jaana M, L Schnell; Silvestri, PAOLA ROSARIA; Liselotte, Skov; Tamar, Steinberg; Friederike Tagwerker Gloor, ; Zsanett, Tarnok; Susanne, Walitza; Elif, Weidinger. - In: BIOLOGICAL PSYCHIATRY. - ISSN 0006-3223. - (2023).
Genome-wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome.
Rizzo R;Cardona F;Porcelli C;Davide Martino;Valentina Baglioni;Valeria Neri;Alessandra Pellico;Paola Rosaria Silvestri;
2023
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
