Data_Sheet_1_Evaluating the association between DNM1L variants and Parkinson's disease in the Chinese population.docx

IntroductionParkinson's disease (PD) is a progressive movement disorder caused by a loss of dopaminergic neurons. Previous studies have highlighted the importance of mitochondria dynamics in the pathogenesis of PD. Dynamin-1-like (DNM1L) is a gene that encodes dynamin-related protein 1 (DRP1), a GTPase essential for proper mitochondria fission. In the present study, we evaluated the relationship between DNM1L variants and PD in the Chinese population.
MethodsA total of 3,879 patients with PD and 2,931 healthy controls were recruited and burden genetic analysis combined with high-throughput sequencing was applied.
ResultsWe identified 23 rare variants in the coding region of DNM1L, while no difference in variant burden was shown between the cases and controls. We also identified 201 common variants in the coding and flanking regions and found two significant SNPs, namely, rs10844308 and rs143794289 [odds ratio (OR) = 1.220 and 0.718, p = 0.025 and 0.036, respectively]. We also performed a meta-analysis to correlate the two SNPs with PD risk. However, none of the common variants was significant using logistic regression.
ConclusionDespite the critical role of DRP1, our study did not support the relationship between DNM1L variants and PD risk in the Chinese population.

引言
帕金森病（Parkinson's disease, PD）是一种由多巴胺能神经元丢失引发的进行性运动障碍。既往研究已证实线粒体动力学在PD发病机制中的重要作用。动力蛋白1样基因（Dynamin-1-like, DNM1L）编码动力蛋白相关蛋白1（Dynamin-related protein 1, DRP1），后者是一种对线粒体正常分裂至关重要的GTP酶。本研究旨在探究中国人群中DNM1L基因变异与PD的关联。
方法
本研究共纳入3879例PD患者与2931例健康对照，采用高通量测序结合变异负荷遗传分析的方法开展研究。
结果
本研究在DNM1L基因编码区共鉴定出23个罕见变异，但病例组与对照组的变异负荷无显著差异。同时在编码区及侧翼区域鉴定出201个常见变异，其中两个单核苷酸多态性（Single Nucleotide Polymorphism, SNP）位点rs10844308与rs143794289具有统计学意义，比值比（Odds Ratio, OR）分别为1.220和0.718，P值分别为0.025和0.036。此外，本研究针对这两个SNP位点与PD风险的关联开展了荟萃分析，但经逻辑回归分析后，所有常见变异均未显示出显著关联。
结论
尽管DRP1发挥着关键作用，但本研究结果并不支持中国人群中DNM1L基因变异与PD风险存在关联。