Author:
Tsetsos Fotis,Topaloudi Apostolia,Jain Pritesh,Yang Zhiyu,Yu Dongmei,Kolovos Petros,Tumer Zeynep,Rizzo Renata,Hartmann Andreas,Depienne Christel,Worbe Yulia,Müller-Vahl Kirsten R.,Cath Danielle C.,Boomsma Dorret I.,Wolanczyk Tomasz,Zekanowski Cezary,Barta Csaba,Nemoda Zsofia,Tarnok Zsanett,Padmanabhuni Shanmukha S.,Buxbaum Joseph D.,Grice Dorothy,Glennon Jeffrey,Stefansson Hreinn,Hengerer Bastian,Yannaki Evangelia,Stamatoyannopoulos John A.,Benaroya-Milshtein Noa,Cardona Francesco,Hedderly Tammy,Heyman Isobel,Huyser Chaim,Mir Pablo,Morer Astrid,Mueller Norbert,Münchau Alexander,Plessen Kerstin J.,Porcelli Cesare,Roessner Veit,Walitza Susanne,Schrag Anette,Martino Davide,Tischfield Jay A.,Heiman Gary A.,Willsey A. Jeremy,Dietrich Andrea,Davis Lea K.,Crowley James,Mathews Carol A.,Scharf Jeremiah M.,Georgitsi Marianthi,Hoekstra Pieter J.,Paschou Peristera, , , , ,
Abstract
AbstractTourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture, characterized by multiple motor tics and at least one vocal tic persisting for more than one year. We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6,133 TS individuals and 13,565 ancestry-matched controls. We identified a genome-wide significant locus on chromosome 5q15 and one array-wide significant locus on chromosome 2q24.2. Integration of eQTL, Hi-C and GWAS data implicated the NR2F1 gene and associated lncRNAs within the 5q15 locus, and the RBMS1 gene within the 2q24.2 locus. Polygenic risk scoring using previous GWAS results demonstrated statistically significant ability to predict TS status in the novel cohort. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring on brain volume data identified statistically significant associations with right and left putamen volumes. Our work presents novel insights in the neurobiology of TS opening up new directions for future studies.
Publisher
Cold Spring Harbor Laboratory