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Genome-Wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome

2023; Elsevier BV; Volume: 96; Issue: 2 Linguagem: Inglês

10.1016/j.biopsych.2023.01.023

1873-2402

Fotis Tsetsos, Apostolia Topaloudi, Pritesh Jain, Zhiyu Yang, Dongmei Yu, Petros Kolovos, Zeynep Tümer, Renata Rizzo, Andreas Hartmann, Christel Depienne, Yulia Worbe, Kirsten Müller‐Vahl, Daniëlle C. Cath, Dorret I. Boomsma, Tomasz Wolañczyk, Cezary Żekanowski, Csaba Barta, Zsófia Nemoda, Zsanett Tárnok, Shanmukha Sampath Padmanabhuni, Joseph D. Buxbaum, Dorothy E. Grice, Jeffrey Glennon, Hreinn Stefánsson, Bastian Hengerer, Evangelia Yannaki, J Stamatoyannopoulos, Noa Benaroya-Milshtein, Francesco Cardona, Tammy Hedderly, Isobel Heyman, Chaim Huyser, Pablo Mir, Àstrid Morer, Norbert Mueller, Alexander Münchau, Kerstin Jessica Plessen, Cesare Porcelli, Veit Roessner, Susanne Walitza, Anette Schrag, Davide Martino, Cathy L. Barr, James R. Batterson, Cheston M. Berlin, Cathy L. Budman, Giovanni Coppola, Nancy J. Cox, Sabrina M. Darrow, Yves Dion, Nelson B. Freimer, Marco A. Grados, Erica Greenberg, Matthew E. Hirschtritt, Alden Y. Huang, Cornelia Illmann, Robert A. King, Roger Kurlan, James F. Leckman, Gholson J. Lyon, Irene A. Malaty, William M. McMahon, Benjamin M. Neale, Michael S. Okun, Lisa Osiecki, Mary M. Robertson, Guy A. Rouleau, Paul Sandor, Harvey S. Singer, Jan Smit, Jae Hoon Sul, Christos Androutsos, Entela Basha, Luca Farkas, Jakub Fichna, Piotr Janik, M. Kapisyzi, Iordanis Karagiannidis, Anastasia Koumoula, Peter Nagy, Joanna Puchala, Natalia Szejko, Urszula Szymańska, Vaia Tsironi, Alan Apter, Juliane Ball, Benjamin Bodmer, Emese Bognár, Judith Buse, Marta Correa Vela, Carolin Fremer, Blanca Garcia-Delgar, Mariangela Gulisano, Annelieke Hagen, Julie Hagstrøm, Marcos Madruga-Garrido, Peter Nagy, Alessandra Pellico, Daphna Ruhrman, Jaana Schnell, Paola Rosaria Silvestri, Liselotte Skov, Tamar Steinberg, Friederike Tagwerker Gloor, Victoria Turner, Elif Weidinger, John J. Alexander, Tamás Arányi, Wim Buisman, Jan K. Buitelaar, Nicole N. Driessen, Petros Drineas, Siyan Fan, Natalie J. Forde, Sarah Gerasch, Odile A. van den Heuvel, Cathrine Jespersgaard, Ahmad S. Kanaan, Harald E. Möller, Muhammad Sulaman Nawaz, Ester Nespoli, Luca Pagliaroli, Geert Poelmans, Petra J. W. Pouwels, Francesca Romana Rizzo, Dick J. Veltman, Ysbrand D. van der Werf, Joanna Widomska, Nuno R. Zilhão, Lawrence W. Brown, Keun‐Ah Cheon, Barbara Coffey, Thomas V. Fernandez, Blanca Garcia-Delgar, Donald L. Gilbert, Julie Hagstrøm, Hyun Ju Hong, Laura Ibanez-Gomez, Eunjoo Kim, Young Key Kim, Young-Shin Kim, Robert A. King, Yun-Joo Koh, Sodahm Kook, Samuel Kuperman, Bennett Leventhal, Marcos Madruga-Garrido, Athanasios Maras, Tara Murphy, Eun-Young Shin, Dong‐Ho Song, Jungeun Song, Matthew W. State, Frank Visscher, Sheng Wang, Samuel H. Zinner, Jay A. Tischfield, Gary A. Heiman, A. Jeremy Willsey, Andrea Dietrich, Lea K. Davis, James J. Crowley, Carol A. Mathews, Jeremiah M. Scharf, Marianthi Georgitsi, Pieter J. Hoekstra, Peristera Paschou,

Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

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.