Genetic Analysis of Six Transmembrane Protein Family Genes in Parkinson’s Disease in a Large Chinese Cohort

作者：Yuwen Zhao, Kailin Zhang, Hongxu Pan, Yige Wang, Xiaoxia Zhou, Yaqin Xiang, Qian Xu, Qiying Sun, Jieqiong Tan, Xinxiang Yan, Jinchen Li, Jifeng Guo, Beisha Tang, Zhenhua Liu · 发表于：Frontiers in Aging Neuroscience · 年份：2022 · DOI：10.3389/fnagi.2022.889057 · 被引用次数：20 · 研究领域：Parkinson's Disease Mechanisms and Treatments、RNA regulation and disease、Nuclear Receptors and Signaling

Objectives Parkinson’s disease (PD) is a neurodegenerative disorder with the manifestation of motor symptoms and non-motor symptoms. Previous studies have indicated the role of several transmembrane (TMEM) protein family genes in PD pathogenesis. Materials and Methods In order to better investigate the genetic role of PD-related TMEM protein family genes in PD, including TMEM230 , TMEM59 , TMEM108 , TMEM163 , TMEM175 , and TMEM229B , 1,917 sporadic early onset PD (sEOPD) or familial PD (FPD) patients and 1,652 healthy controls were analyzed by whole-exome sequencing (WES) while 1,962 sporadic late-onset PD (sLOPD) and 1,279 healthy controls were analyzed by whole-genome sequencing (WGS). Rare and common variants for each gene were included in the analysis. Results One hundred rare damaging or loss of function variants of six genes were found at the threshold of MAF < 0.1%. Three rare Dmis variants of TMEM230 were specifically identified in PD. Rare missense variants of TMEM59 were statistically significantly associated with PD in the WES cohort, indicating the role of TMEM59 in FPD and sEOPD. Rare missense variants of TMEM108 were suggestively associated with PD in the WGS cohort, indicating the potential role of TMEM108 in sLOPD. The rare variant of the other three genes and common variants of six genes were not significantly associated with PD. Conclusion We performed a large case-control study to systematically investigate the role of several PD-related TMEM protein...