Senkevich Konstantin, Parlar Sitki Cem, Chantereault Cloe, Yu Eric, Ahmad Jamil, Ruskey Jennifer A, Asayesh Farnaz, Spiegelman Dan, Waters Cheryl, Monchi Oury, Dauvilliers Yves, Dupré Nicolas, Miliukhina Irina, Timofeeva Alla, Emelyanov Anton, Pchelina Sofya, Greenbaum Lior, Hassin-Baer Sharon, Alcalay Roy N, Gan-Or Ziv
The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada.
Department of Neurology and neurosurgery, McGill University, Montréal, QC, Canada.
NPJ Parkinsons Dis. 2024 Oct 25;10(1):201. doi: 10.1038/s41531-024-00809-9.
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).
先前的研究已经证实，罕见的双等位基因SYNJ1突变会导致常染色体隐性帕金森综合征和帕金森病（PD）。我们分析了8165例PD病例、818例早发性帕金森病（EOPD，年龄<50岁）以及70363名对照。负荷荟萃分析显示，Sac1 SYNJ1结构域中罕见的非同义变异以及综合注释依赖损耗评分较高（>20）的变异与PD之间存在关联（错误发现率校正P值=0.040）。对EOPD患者的荟萃分析表明，所有罕见的杂合SYNJ1变异与PD之间存在关联（错误发现率校正P值=0.029）。
