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Are rare heterozygous SYNJ1 variants associated with Parkinson's disease?
Konstantin Senkevich1,2,3, Sitki Cem Parlar4,5, Cloe Chantereault4,5
1The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada. konstantin.senkevich@mcgill.ca.
Abstract:
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).
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