Members of the transmembrane (TMEM) protein family have been identified to be associated with Parkinson's disease (PD) and other neurodegenerative disorders. However, most studies were based on the European-ancestry population and were still awaiting replications. Here, we aimed to systematically evaluate the associations of TMEMs with PD in a large Chinese early-onset PD (EOPD, age at onset <50 years) cohort. We identified rare variants (minor allele frequency <0.01) in 743 unrelated EOPD patients using whole-exome sequencing and evaluated the association between variants and EOPD at allele and gene levels. Totally 45 rare variants were identified in 6 TMEM protein family members. At allele level, p.176 K>E in TMEM175 and p.33P>R in TMEM163 were significantly associated with PD. Gene-based burden analysis showed a clear enrichment of TMEM163 variants in EOPD. Our work identifies 2 novel rare variants and TMEM163 as potential risk factors for PD provide a better understanding of the genetic involvement of TMEM protein family members in EOPD and broadens the current mutation spectrum of PD.
Keywords: Early-onset Parkinson’s disease; Genetics; Mutation; TMEMs.
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