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.

中文翻译：

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缺乏关于鞘脂蛋白酶A，B，C和D与帕金森氏病遗传关联的证据

PSAP基因编码prosaposin，随后被切割成四个活性saposin：saposin A，B，C和D。这些酶的突变与特定的溶酶体贮积症有关。最近，已经报道了saposin D突变与帕金森病（PD）之间的遗传关联。为了进一步检查saposin D或其他saposin的变体是否可能与帕金森氏病相关，我们对4,132例帕金森氏病患者和4,470名对照进行了优化序列核关联试验（SKAT-O）。此外，我们分析了来自PD基因组广泛关联研究（GWAS）的数据，以检查PSAP基因座中常见变异与帕金森氏病风险（对56,308例患者进行分析）和发病年龄（对28,568例患者进行分析）之间的关联。我们没有发现saposin D中罕见的或常见的变体，或其他saposin中的任何变体与PD风险或发作之间没有任何统计学上的显着关联。这些结果表明，PSAP变异体在PD中的作用很小，或更可能没有作用。