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全基因组关联研究确定DRAM1与台湾抽动秽语综合征相关。

Genome-wide association study identifies DRAM1 associated with Tourette syndrome in Taiwan.

作者信息

Lin Wei-De, Liu Ting-Yuan, Chen Yu-Chia, Chou I-Ching, Tsai Fuu-Jen

机构信息

Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; School of Post Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan.

Million-person precision medicine initiative, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.

出版信息

Biomed J. 2024 Dec;47(6):100725. doi: 10.1016/j.bj.2024.100725. Epub 2024 Apr 10.

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 1007 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) 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

图雷特综合征(TS)是一种以运动和发声抽动为特征的神经发育障碍。先前在欧洲血统人群中通过全基因组关联研究(GWAS)已确定了几个与TS相关的易感基因座。然而,TS的确切致病机制尚不清楚;此外,先前TS的GWAS结果基于西方人群,可能不适用于其他人群。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

对一个台湾TS/CTD队列进行GWAS,该队列包括1007例TS患者和25522例血统匹配的对照。此外,计算并评估了多基因风险评分。

结果

在12号染色体q23.2区域鉴定出全基因组显著位点rs12313062(p = 1.43×10)以及其他9个单核苷酸多态性,与DRAM1相关,是TS/CTD组中鉴定出的一个新的易感基因座。DRAM1是一种受p53调节的溶酶体跨膜蛋白,可调节自噬和凋亡,可能与自噬破坏相关的神经精神疾病有关。

结论

本研究首次在台湾人群中对TS进行了GWAS,在12号染色体q23.2区域鉴定出一个与DRAM1相关的显著位点。这些发现为TS的神经生物学提供了新的见解,并为该领域未来的研究提供了潜在方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de3/11550159/46a60d537d02/gr1.jpg

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