%0 Journal Article
%T Genome-wide association study identifies DRAM1 associated with Tourette syndrome in Taiwan.
%A Lin WD
%A Liu TY
%A Chen YC
%A Chou IC
%A Tsai FJ
%J Biomed J
%V 0
%N 0
%D 2024 Apr 10
%M 38608873
%F 7.892
%R 10.1016/j.bj.2024.100725
%X <B>BACKGROUND: </B>Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. Several susceptibility loci associated with TS have been identified previously in populations of European descent using genome-wide association studies (GWAS). However, the exact pathogenic mechanism underlying TS is unknown; additionally, the results of previous GWAS for TS were based on Western populations, which may not translate to other populations. Therefore, we conducted a GWAS in Taiwanese patients with TS and chronic tic disorders (CTDs), with an aim to elucidate the genetic basis and potential risk factors for TS in this population.<BR><B>METHODS: </B>GWAS was performed on a Taiwanese TS/CTDs cohort with a sample size of 1,007 patients with TS and 25,522 ancestry-matched controls. Additionally, polygenic risk score was calculated and assessed.<BR><B>RESULTS: </B>Genome-wide significant locus, rs12313062 (p=1.43 × 10-8) and other 9 single nucleotide polymorphisms, were identified in chromosomes 12q23.2, associated with DRAM1 and was a novel susceptibility locus identified in TS/CTDs group. DRAM1, a lysosomal transmembrane protein regulated by p53, modulates autophagy and apoptosis, with potential implications for neuropsychiatric conditions associated with autophagy disruption.<BR><B>CONCLUSIONS: </B>This study conducted the first GWAS for TS in a Taiwanese population, identifying a significant locus on chromosome 12q23.2 associated with DRAM1. These findings provide novel insights into the neurobiology of TS and potential directions for future research in this area.