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Data from: Effect of polygenic load on striatal dopaminergic deterioration in Parkinson's disease


Lee, Myung Jun et al. (2019), Data from: Effect of polygenic load on striatal dopaminergic deterioration in Parkinson's disease, Dryad, Dataset,


Objective: To investigate the effect of polygenic load on the progression of striatal dopaminergic dysfunction in patients with Parkinson's disease (PD). Methods: Using data from 335 PD patients in the Parkinson's Progression Markers Initiative (PPMI) database, we investigated the longitudinal association of PD-associated polygenic load with changes in striatal dopaminergic activity as measured by 123I-N-3-fluoropropyl-2-beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane (123I-FP-CIT) single photon emission computed tomography (SPECT) over 4 years. PD-associated polygenic load was estimated by calculating weighted genetic risk scores (GRS) using: i) all available 27 PD-risk single nucleotide polymorphisms (SNPs) in the PPMI database (GRS1); and ii) 23 SNPs with minor allele frequency > 0.05 (GRS2). Results: GRS1 and GRS2 were correlated with younger age-at-onset in PD patients (GRS1, Spearman's rho = -0.128, p = 0.019; GRS2, Spearman's rho = -0.109, p = 0.047). Although GRS1 did not show an association with changes in striatal 123I-FP-CIT availability, GRS2 was associated with a slower decline of striatal dopaminergic activity (interactions with disease duration in linear mixed model; caudate nucleus, estimate = 0.399, SE = 0.165, p = 0.028; putamen, estimate = 0.396, SE = 0.137, p = 0.016). Conclusions: Our results suggest that genetic factors for PD risk may have heterogeneous effects on the striatal dopaminergic degeneration, and some factors may be associated with a slower decline of dopaminergic activity. Composition of PD-progression specific GRS may be useful in predicting disease progression in patients.

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