Are rare heterozygous SYNJ1 variants associated with Parkinson's disease?

Konstantin A. Senkevich; Sitki Cem Parlar; Cloe Chantereault; Eric Yu; Jamil Ahmad; Jennifer A. Ruskey; Farnaz Asayesh; Dan Spiegelman; Cheryl Waters; Oury Monchi; Yves A Dauvilliers; Nicolas Dupré; Irina V. Miliukhina; Alla Timofeeva; Anton Emelyanov; Sofya Pchelina; Lior Greenbaum; Sharon Hassin‐Baer; Roy N. Alcalay; Ziv Gan‐Or

doi:10.1038/s41531-024-00809-9

Genetic & Genomic Medicinenpj Parkinson s DiseaseOct 25, 2024

Peer-reviewed journal article

Are rare heterozygous SYNJ1 variants associated with Parkinson's disease?

Konstantin A. Senkevich iD, Sitki Cem Parlar iD, Cloe Chantereault, Eric Yu iD, Jamil Ahmad, Jennifer A. Ruskey iD, Farnaz Asayesh iD, Dan Spiegelman iD, Cheryl Waters iD, Oury Monchi iD, Yves A Dauvilliers iD, Nicolas Dupré iD, Irina V. Miliukhina iD, Alla Timofeeva iD, Anton Emelyanov iD, Sofya Pchelina iD, Lior Greenbaum iD, Sharon Hassin‐Baer iD, Roy N. Alcalay iD, Ziv Gan‐Or iD

Abstract

Previous studies have suggested that rare biallelic SYNJ1 mutations may cause autosomal recessive parkinsonism and Parkinsons disease (PD). Our study explored the impact of rare SYNJ1 variants in non-familial settings, including 8,165 PD cases, 818 early-onset PD (EOPD, <50 years) and 70,363 controls. Burden meta-analysis using optimized sequence Kernel association test (SKAT-O) revealed an association between rare nonsynonymous variants in the Sac1 SYNJ1 domain and PD (Pfdr=0.040). Additionally, a meta-analysis focusing on patients with EOPD demonstrated an association between all rare SYNJ1 variants and PD (Pfdr=0.029). Rare SYNJ1 variants may be associated with sporadic PD, and more specifically with EOPD.

PDF DOI