Are rare heterozygous SYNJ1 variants associated with Parkinson’s disease?
Previous studies have established that rare biallelic SYNJ1 mutations cause autosomal recessive parkinsonism and Parkinson's disease (PD). We analyzed 8165 PD cases, 818 early-onset-PD (EOPD, < 50 years) and 70,363 controls. Burden meta-analysis revealed an association between rare nonsynonymous variants and variants with high Combined Annotation-Dependent Depletion score (> 20) in the Sac1 SYNJ1 domain and PD (Pfdr = 0.040). A meta-analysis of EOPD patients demonstrated an association between all rare heterozygous SYNJ1 variants and PD (Pfdr = 0.029).
Authors
- Konstantin A. Senkevich (ORCID: https://orcid.org/0000-0003-3407-5716)
- Farnaz Asayesh
- Cheryl Waters (ORCID: https://orcid.org/0000-0002-1908-8773)
- Jennifer A. Ruskey (ORCID: https://orcid.org/0000-0002-6392-5014)
- Oury Monchi (ORCID: https://orcid.org/0000-0003-2148-5409)
- Sharon Hassin‐Baer (ORCID: https://orcid.org/0000-0001-7657-0171)
- Dan Spiegelman (ORCID: https://orcid.org/0000-0001-6450-3238)
- Sitki Cem Parlar (ORCID: https://orcid.org/0009-0003-9026-114X)
- Irina Miliukhina (ORCID: https://orcid.org/0000-0002-6433-542X)
- Lior Greenbaum (ORCID: https://orcid.org/0000-0001-6176-0941)
- Eric Yu (ORCID: https://orcid.org/0000-0003-3525-4564)
- Nicolas Dupré (ORCID: https://orcid.org/0000-0001-7270-6115)
- Yves A Dauvilliers (ORCID: https://orcid.org/0000-0003-0683-6506)
- Ziv Gan‐Or (ORCID: https://orcid.org/0000-0003-0332-234X)
- Cloe Chantereault
- Jamil Ahmad (ORCID: https://orcid.org/0000-0003-4594-2723)
- Alla Timofeeva (ORCID: https://orcid.org/0000-0003-1661-7753)
- Anton Emelyanov (ORCID: https://orcid.org/0000-0002-3249-7889)
- Roy N. Alcalay
- Sofya Pchelina
Institutions
- Montreal Neurological Institute and Hospital (CA)
- Tel Aviv University (IL)
- Université de Montpellier (FR)
- First Pavlov State Medical University of St. Petersburg (RU)
- Tel Aviv Sourasky Medical Center (IL)
- Sheba Medical Center (IL)
- McGill University Health Centre (CA)
- Institute of the Human Brain (RU)
- McGill Genome Centre (CA)
- Institut Universitaire de Gériatrie de Montréal (CA)
- Université Laval (CA)
- McGill University (CA)
- Université de Montréal (CA)
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2024-10-25
- DOI
- https://doi.org/10.1038/s41531-024-00809-9
- Citations
- 2
- Primary Topic
- Neurological disorders and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.74
Funders
- Michael J. Fox Foundation for Parkinson's Research
- Brookdale Foundation
- McGill University
- Parkinson's Foundation
- Consortium canadien en neurodégénérescence associée au vieillissement
- Parkinson Canada
- Canada First Research Excellence Fund
- National Institutes of Health
- Fonds de Recherche du Québec - Santé
- National Institute of Neurological Disorders and Stroke