AUTHOR=Zhao Yuwen , Zhang Kailin , Pan Hongxu , Wang Yige , Zhou Xiaoxia , Xiang Yaqin , Xu Qian , Sun Qiying , Tan Jieqiong , Yan Xinxiang , Li Jinchen , Guo Jifeng , Tang Beisha , Liu Zhenhua 

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=14

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.889057

DOI=10.3389/fnagi.2022.889057

ISSN=1663-4365

ABSTRACT=<sec><title>Objectives</title><p>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.</p></sec><sec><title>Materials and Methods</title><p>In order to better investigate the genetic role of PD-related TMEM protein family genes in PD, including <italic>TMEM230</italic>, <italic>TMEM59</italic>, <italic>TMEM108</italic>, <italic>TMEM163</italic>, <italic>TMEM175</italic>, and <italic>TMEM229B</italic>, 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.</p></sec><sec><title>Results</title><p>One hundred rare damaging or loss of function variants of six genes were found at the threshold of MAF &lt; 0.1%. Three rare Dmis variants of <italic>TMEM230</italic> were specifically identified in PD. Rare missense variants of <italic>TMEM59</italic> were statistically significantly associated with PD in the WES cohort, indicating the role of <italic>TMEM59</italic> in FPD and sEOPD. Rare missense variants of <italic>TMEM108</italic> were suggestively associated with PD in the WGS cohort, indicating the potential role of <italic>TMEM108</italic> in sLOPD. The rare variant of the other three genes and common variants of six genes were not significantly associated with PD.</p></sec><sec><title>Conclusion</title><p>We performed a large case-control study to systematically investigate the role of several PD-related TMEM protein family genes in PD. We identified three PD-specific variants in <italic>TMEM230</italic>, the significant association of <italic>TMEM59</italic> with FPD, and sEOPD and the suggestive association of <italic>TMEM108</italic> with sLOPD.</p></sec>