The effect of the PARK16 rs11240572 variant on brain structure in Parkinson's disease

Abstract

BackgroundIncreasing evidence suggests that genetic factors play a key role in the development of Parkinson's disease (PD). The variant rs11240572 in the PARK16 gene locus is strongly associated with PD. However, its effect on the pathogenesis of PD is yet to be clari ed. ObjectiveTo explore the effect of the PARK16 rs11240572 variant on brain structure in PD patients. MethodsA total of 51 PD patients were enrolled in the study and genotyped for the rs11240572 variant. Clinical assessments and MRI scans were conducted across all participants. Voxel-based morphometry (VBM) was used to investigate gray matter volume (GMV) of the whole brain between these two groups.Correlation analysis was performed to identify the relationships between GMV and clinical features. ResultsThere were 17 rs11240572-A variant carriers and 34 non-carriers, with no signi cant demographic differences between these two groups. Compared with non-carriers, rs11240572-A carriers showed increased GMV in left caudate nucleus and putamen, but decreased GMV in left superior temporal gyrus and supramarginal gyrus. In non-carriers, left basal ganglia GMV was positively correlated with UPDRS III (r = 0.365, p = 0.040) and bradykinesia (r = 0.409, p = 0.020), but negatively correlated with MMSE (r = -0.391, p = 0.027). When reduced the sample size to the level of the carrier sample, we still found the same correlations in the non-carrier group. However, no correlation was found between the altered GMV and clinical features in the carriers. ConclusionsOur study showed that the PARK16 rs11240572 variant affects the brain structure of patients with PD, especially in the basal ganglia and temporoparietal cortex. This indicated that this variant might play an important role in the pathogenesis of PD.

The structural changes of gray matter in Parkinson disease patients with mild cognitive impairments

“…The increased GMV in the putamen in the PD patients with NCI was unexpected but was consistent with the previous studies [ 57 , 58 ], and may support the concept of striatum compensation in PD. The putamen is the striatal nucleus mainly linked with motor performance.…”

Parkinson’s Disease Risk Variant rs9638616 is Non-Specifically Associated with Altered Brain Structure and Function

“…This may be reflected in our non-significant interaction effects. On the other hand, the association of rs9638616 and brain imaging measures has not previously been investigated, and studies of similar or smaller sample sizes have shown significant associations for SNVs with brain phenotype [16][17][18][21][22][23][24][25][26][27]. Based on comparable imaging genetic studies of individual risk variants and PD brain phenotypes, our study is sufficiently powered for similar-sized effects (Supplementary Material 1).…”

“…Secondly, connectivity of functional MRI (fMRI) networks has been studied extensively in PD, showing reorganization along the disease course [14], correlation with non-motor symptoms in early PD [14,15], and relation to PD genetic markers [16][17][18]. Third, cortical grey matter volume is reduced beginning in the early stages of PD, in particular in those with cognitive impairment [19,20], and is also related to PD genetic markers [21,22].…”

“…Imaging-genetic studies of PD have analyzed individual candidate genes and single-nucleotide variants (SNVs) in sample sizes in the range of tens to hundreds [16][17][18][21][22][23][24][25][26][27], finding varied associations to brain structure and function. Indeed, despite brain microstructure and function undergoing a complex regulation, these studies show that multiple different SNVs are individually penetrant for MRI-derived brain phenotypes [16][17][18][21][22][23][24][25][26][27].…”

“…Imaging-genetic studies of PD have analyzed individual candidate genes and single-nucleotide variants (SNVs) in sample sizes in the range of tens to hundreds [16][17][18][21][22][23][24][25][26][27], finding varied associations to brain structure and function. Indeed, despite brain microstructure and function undergoing a complex regulation, these studies show that multiple different SNVs are individually penetrant for MRI-derived brain phenotypes [16][17][18][21][22][23][24][25][26][27]. However, no study has evaluated rs9638616, no study has assessed a range of voxelwise measures of tract microstructure, functional connectivity or cortical morphology together in a candidate-SNV approach, and no study has investigated whether brain changes mediate the relationship between genotype and PD-associated symptoms, which could provide causal evidence for a pathophysiological mechanism [28].…”