4.4 Article

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

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NATURE AGING
卷 1, 期 8, 页码 734-+

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SPRINGERNATURE
DOI: 10.1038/s43587-021-00088-6

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资金

  1. MJFF
  2. Intramural Research Program of the National Institutes of Health, National Institute on Aging
  3. National Institute of Neurological Disorders and Stroke at the National Institutes of Health - Celgene
  4. Celgene
  5. GlaxoSmithKline
  6. National Institute of Neurological Disorders and Stroke
  7. Pfizer
  8. Sanofi
  9. Verily
  10. [12749]
  11. [12749.01]
  12. [14696]

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The study sequenced 4,871 whole-blood RNA samples from 1,570 PD patients and found significant changes in RNA expression in PD patients, including increased neutrophil gene expression and decreased lymphocyte counts.
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. The authors report whole-blood RNA-seq for 4,871 samples from 1,570 participants in the Parkinson Progression Marker Initiative. This Resource documents blood-based transcriptomic changes associated with PD, including early increases in neutrophil gene expression with a decrease in lymphocytes.

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