Lack of evidence for genetic association of saposins A, B, C and D with Parkinson disease

The PSAP gene encodes prosaposin, which is later cleaved into four active saposins: saposin A, B, C and D. Mutations in these enzymes have been linked to specific lysosomal storage disorders. Recently, a genetic association between mutations in saposin D and Parkinson disease (PD) has been reported. To further examine whether variants in saposin D or the other saposins could be associated with Parkinson s disease, we performed Optimized Sequence Kernel Association Test (SKAT-O) in 4,132 Parkinson s disease patients and 4,470 controls. Furthermore, we analyzed data from a PD Genome Wide Association Study (GWAS) to examine the association of common variants in the PSAP locus with Parkinson s disease risk (analysis on 56,308 patients) and age at onset (analysis on 28,568 patients). We did not find any statistically significant associations between neither rare nor common variants in saposin D, nor any of the other saposins, and PD risk or onset. These results suggest that PSAP variants play either a very minor role, or more likely, no role, in PD.