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.
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。