Objective:

To identify single nucleotide variants (SNVs) that are associated with Parkinson’s disease (PD) with dementia (PDD), using genome-wide survival study (GWSS) and polygenic risk score (PRS) related to Alzheimer’s disease (AD), PD and amyloid b (Ab) deposition.

Background:

Genome-wide association studies revealed significant genetic variants associated with Parkinson’s disease (PD), but genetic variants for PDD are under investigation.

Design/Methods:

We recruited patients with PD between January 2009 and December 2016 and performed genomic sequencing analysis using a Korean chip. First, we conducted GWSS. Second, PRS was constructed with variants obtained from previous PRS studies for PD, AD, and amyloid positivity. The association between PRS and dementia incidence was evaluated with Cox proportional hazard models.

Results:

Among the 964 final study subjects, 225 patients were diagnosed with dementia after a median follow-up duration of 10 years. In GWSS, we found that SNVs in the HS1BP3, PTPRM, APOE, and TOMM40 were associated with the development of PDD. Asian AD-PRS (PGS000779) was significantly associated with increased risk of PDD (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.19−1.45, P-value <0.001). European AD-PRS (PGS0002280) was also associated with increased risk of PDD (HR 1.89, 95% CI 1.23–2.91, P=0.004). In addition, Ab-PRS was associated with increased risk of dementia in PD (HR, 2.07; 95% CI, 1.17–3.65, P=0.012). However, PD-PRS was not significantly associated with PDD.

Conclusions:

We identified that AD-PRS and Ab-PRS were significantly associated with the development of dementia in PD. These results may be useful information to elucidate pathogenic mechanisms and develop potential treatments strategy for PDD.