No effect of Parkinson's disease-polygenic load on striatal density of dopaminergic neuron in healthy subjects.

OBJECTIVE

There has been increasing evidence to support the role of genetic factors in Parkinson's disease (PD). I-FP-CIT single-photon emission computed tomography (SPECT) enables in vivo visualization of the striatal density of dopaminergic neuron.

METHODS

We investigated the association between PD-associated polygenic load and striatal density of dopaminergic neuron in healthy subjects. Data used in the preparation of this article were obtained from Parkinson's Progression Markers Initiative database. I-FP-CIT SPECT was performed for all subjects. Specific binding ratios (SBRs) were calculated from the ventral striatum, caudate nucleus, and putamen with reference to cerebellum. Singe nucleotide polymorphism (SNP) genotyping from the PPMI database was adopted in calculating genetic risk score (GRS). GRS was defined as the sum of the number of risk alleles weighted by log odds ratios for PD. We calculated three GRSs using three different sets of SNPs.

RESULT

A total of 151 subjects were included in this study (101 males, 50 females). GRS1, GRS2 and GRS3 were significantly different with the highest scores of GRS1. Multiple regression was done to investigate whether striatal SBRs are influenced by GRSs after adjusting for age and sex. However, none of GRSs were associated with SBRs of the ventral striatum, caudate nucleus and putamen.

CONCLUSION

PD risk SNPs weighted by odds ratio for PD were not associated with SBRs measured from SPECT in healthy subjects. Therefore, there is no effect of PD-associated polygenic load on striatal density of dopaminergic neuron in healthy subjects.