Mutation analysis of TMEM family members for early-onset Parkinson's disease in Chinese population

Abstract

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.