Objective: To assess whether GWAS identified Parkinson’s disease (PD) risk loci also influence symptom progression among patients. 

Background: Genetic factors have a considerable influence on PD susceptibility. The largest genome-wide association study identified 26 independent single-nucleotide polymorphisms (SNPs) associated with PD risk. Among patients, the course and severity of symptom progression is variable, and little is known about the potential impact of these genetic factors on phenotypic variance.

Methods: We genotyped 23 SNPs in our longitudinal cohort of 246 incident PD patients, followed on average over 5 years and 7.5 years into disease. Movement disorder specialists repeatedly assessed PD symptom progression. The combined impact of PD risk loci on fast motor symptom progression and cognitive decline was assessed by logistic regression analyses using a weighted genetic risk score.

Results: The weighted genetic risk score was significantly associated with fast motor symptom decline, defined as those in the top quartile of UPDRS-III change over follow-up (OR=1.47, 95% CI=1.02, 2.12).  Furthermore, the risk score was associated with fast cognitive decline, those in the top quartile of change in MMSE score (OR=1.43, 95% CI=1.01, 2.03).

Conclusions: Overall, our study indicates that a cumulative genetic risk, based on PD susceptibility SNPs, is associated with faster motor and cognitive symptom decline.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsons-disease-gwas-risk-loci-and-symptom-progression/