Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：Tourette综合征（TS）是一种神经发育障碍，以运动和发声抽动为特征。先前已使用全基因组关联研究（GWAS）在欧洲血统人群中鉴定了与TS相关的几个易感基因座。然而,TS的确切致病机制尚不清楚；此外，以前TS的GWAS结果是基于西方人群，这可能无法转化为其他人群。因此,我们对台湾TS和慢性抽动障碍（CTD）患者进行了GWAS，旨在阐明该人群中TS的遗传基础和潜在危险因素。
方法：GWAS是对台湾TS/CTDs队列进行的，样本量为1,007名TS患者和25,522名血统匹配的对照。此外,计算并评估多基因风险评分.
结果：全基因组显著基因座，rs12313062(p=1.43×10-8)等9个单核苷酸多态性,在染色体12q23.2中鉴定，与DRAM1相关，并且是在TS/CTDs组中鉴定出的新的易感基因座。DRAM1是一种由p53调控的溶酶体跨膜蛋白，可调节自噬和凋亡，与自噬破坏相关的神经精神疾病的潜在影响。
结论：这项研究在台湾人群中进行了首次针对TS的GWAS，鉴定染色体12q23.2上与DRAM1相关的重要基因座。这些发现为TS的神经生物学提供了新的见解，并为该领域的未来研究提供了潜在的方向。
方法：GWAS是对台湾TS/CTDs队列进行的，样本量为1,007名TS患者和25,522名血统匹配的对照。此外,计算并评估多基因风险评分.
结果：全基因组显著基因座，rs12313062(p=1.43×10-8)等9个单核苷酸多态性,在染色体12q23.2中鉴定，与DRAM1相关，并且是在TS/CTDs组中鉴定出的新的易感基因座。DRAM1是一种由p53调控的溶酶体跨膜蛋白，可调节自噬和凋亡，与自噬破坏相关的神经精神疾病的潜在影响。
结论：这项研究在台湾人群中进行了首次针对TS的GWAS，鉴定染色体12q23.2上与DRAM1相关的重要基因座。这些发现为TS的神经生物学提供了新的见解，并为该领域的未来研究提供了潜在的方向。
