Systematically analyzing rare variants of autosomal-dominant genes for sporadic Parkinson's disease in a Chinese cohort

Abstract Studies have shown that rare variants of Mendelian genes for Parkinson's disease (PD) contribute to sporadic PD in the Caucasian population, which lacked confirmation in the Chinese population. Because the autosomal-dominant PD (AD-PD) had a phenotype closely resembling sporadic PD, we performed a systematic analysis of 7 AD-PD genes ( SNCA , LRRK2 , GIGYF2 , VPS35 , EIF4G1 , DNAJC13 , and CHCHD2 ) in 1456 Chinese sporadic PD patients and 1568 controls. Overall, 72 rare variants were identified, 7 of which were classified as likely pathogenic, 63 of which were categorized as of uncertain significance, and 2 of them were predicted to be likely benign. These AD-PD genes represented a clear enrichment of rare variants in PD patients from a burden analysis ( p  = 0.003), and significant differences could still be observed when likely pathogenic variants were removed ( p  = 0.027). The gene-based association testing also reached significance for LRRK2 ( p  = 0.004) and remained statistically significant after the Bonferroni correction. This report suggested that rare variants of AD-PD genes had a role in the Chinese sporadic PD cohort, especially for those rare variants of LRRK2 .