Exome sequencing in Asian populations identifies low-frequency and rare coding variation influencing Parkinson's disease risk.

ABSTRACT: Parkinson's disease (PD) is an incurable, progressive and common movement disorder that is increasing in incidence globally because of population aging. We hypothesized that the landscape of rare, protein-altering variants could provide further insights into disease pathogenesis. Here we performed whole-exome sequencing followed by gene-based tests on 4,298 PD cases and 5,512 controls of Asian ancestry. We showed that GBA1 and SMPD1 were significantly associated with PD risk, with replication in a further 5,585 PD cases and 5,642 controls. We further refined variant classification using in vitro assays and showed that SMPD1 variants with reduced enzymatic activity display the strongest association (<44% activity, odds ratio (OR) = 2.24, P = 1.25 × 10^-15) with PD risk. Moreover,

SUBMITTER: Chew EG 

PROVIDER: S-EPMC11839463 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature