Rare Variants May Influence Disease Risk and Clinical Features in Sporadic Late-Onset Chinese Parkinson’s Disease Patients

BackgroundThe heritability in Parkinson’s disease (PD) may be contributed by rare variants (RVs) in candidate genes. Currently there is limited genetic data on Chinese PD patients.ObjectiveWe aim to identify RVs in Chinese PD patients and investigate their relationships with risk and phenotype of PD.MethodsWe performed targeted exome sequencing of 29 PD genes on 311 late-onset, sporadic Chinese PD patients. Burden of total and individual RVs (minor allele frequency <0.05 or novel in East Asians that were likely deleterious using in silico prediction tools) were compared to 699 local controls. Gene-based RV carrier status in PD patients was examined for correlation with motor and non-motor phenotypic characteristics.ResultsIn total, 174 RVs were identified in 27 of the 29 genes. Mean RV burden was higher (1.178 vs 0.478, p=1.26×10-24) and HLA-DRB5 p.Val104ArgfsTer26 was enriched in PD patients (0.207 vs 0.000, p<0.0003) compared with controls. Variant carrier status of LRRK2, HLA-DRB5 was associated with tremor, SREBF1 with gait disturbance, SYNJ1 and SCARB2 with motor fluctuations, and PLA2G6 with dyskinesias. Age of onset and neuropsychiatric symptoms were associated with GBA variants, and olfactory deficit, autonomic disturbance, anxiety and depression were associated with variants in SLC44A1, HLA-DRB5, SCARB2 respectively.ConclusionsOur results provided information on rare variant burden in Chinese PD patients and illustrated that there is an important genetic influence on the risk and clinical features in sporadic PD. Further studies are warranted to correlate these genes with putative pathogenic pathways.