Dysregulation of the causative genes for hereditary parkinsonism in the midbrain in Parkinson's disease

ABSTRACT Background and Objectives Many hereditary movement disorders with complex phenotypes without a locus symbol prefix for familial PD present as parkinsonism; however, the dysregulation of genes associated with these phenotypes in the SNpc of PD patients has not been systematically studied. Methods Gene set enrichment analyses were performed using 10 previously published genome‐wide expression datasets obtained by laser‐captured microdissection of pigmented neurons in the SNpc. A custom‐curated gene set for hereditary parkinsonism consisting of causative genes (n = 78) related to disorders with a parkinsonism phenotype, but not necessarily idiopathic or monogenic PD, was constructed from the Online Mendelian Inheritance in Man database. Results In 9 of the 10 gene expression data sets, gene set enrichment analysis showed that the disease‐causing genes for hereditary parkinsonism were downregulated in the SNpc in PD patients compared to controls (nominal P values