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. 2021 Aug;1(8):734-747.
doi: 10.1038/s43587-021-00088-6. Epub 2021 Aug 5.

RNA sequencing of whole blood reveals early alterations in immune cells and gene expression in Parkinson's disease

David W Craig #  1 , Elizabeth Hutchins #  2 , Ivo Violich  1 , Eric Alsop  2 , J Raphael Gibbs  3 , Shawn Levy  4 , Madison Robison  4 , Nripesh Prasad  4 , Tatiana Foroud  5 , Karen L Crawford  6 , Arthur W Toga  6 , Timothy G Whitsett  2 , Seungchan Kim  7 , Bradford Casey  8 , Alyssa Reimer  8 , Samantha J Hutten  8 , Mark Frasier  8 , Fabian Kern  9 , Tobias Fehlman  9 , Andreas Keller  9 , Mark R Cookson  3 , Kendall Van Keuren-Jensen  10 ; Parkinson Progression Marker Initiative
Collaborators, Affiliations

RNA sequencing of whole blood reveals early alterations in immune cells and gene expression in Parkinson's disease

David W Craig et al. Nat Aging. 2021 Aug.

Abstract

Changes in the blood-based RNA transcriptome have the potential to inform biomarkers of Parkinson's disease (PD) progression. Here we sequenced a discovery set of whole-blood RNA species in 4,871 longitudinally collected samples from 1,570 clinically phenotyped individuals from the Parkinson's Progression Marker Initiative (PPMI) cohort. Samples were sequenced to an average of 100 million read pairs to create a high-quality transcriptome. Participants with PD in the PPMI had significantly altered RNA expression (>2,000 differentially expressed genes), including an early and persistent increase in neutrophil gene expression, with a concomitant decrease in lymphocyte cell counts. This was validated in a cohort from the Parkinson's Disease Biomarkers Program (PDBP) consisting of 1,599 participants and by alterations in immune cell subtypes. This publicly available transcriptomic dataset, coupled with available detailed clinical data, provides new insights into PD biological processes impacting whole blood and new paths for developing diagnostic and prognostic PD biomarkers.

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