Are rare heterozygous variants associated with Parkinson's disease?

Previous studies have suggested that rare biallelic mutations may cause autosomal recessive parkinsonism and Parkinson's disease (PD). Our study explored the impact of rare 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 (P=0.040). Additionally, a meta-analysis focusing on patients with EOPD demonstrated an association between all rare variants and PD (P=0.029). Rare variants may be associated with sporadic PD, and more specifically with EOPD.