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An increasing number of identified Parkinson's disease (PD) risk loci contain genes highly expressed in innate immune cells, yet their potential role in pathological mechanisms is not obvious. We have generated transcriptomic profiles of CD14+ monocytes from 230 individuals with sporadic PD and age-matched healthy subjects. We identified dysregulation of genes involved in mitochondrial and proteasomal function. We also generated transcriptomic profiles of primary microglia from autopsied brains of 55 PD and control subjects and observed discordant transcriptomic signatures of mitochondrial genes in PD monocytes and microglia. We further identified PD susceptibility genes, whose expression, relative to each risk allele, is altered in monocytes. These findings reveal that transcriptomic mitochondrial alterations are detectable in PD monocytes and are distinct from brain microglia, and facilitates efforts to understand the roles of myeloid cells in PD. ### Competing Interest Statement A.M.G. served on the scientific advisory board for Denali Therapeutics from 2015-2018 and has served as a consultant to AbbVie, Biogen, Eisai, Illumina, and GSK. R.S-P. and S.B. have served as consultants to Denali Therapeutics. R.H.W. has served as a consultant to Neurocine Biosciences, Inc. Other authors declare no competing financial interests.

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