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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npj Parkinson's Disease Open Access 02 February 2023
Transcriptome deregulation of peripheral monocytes and whole blood in GBA-related Parkinson’s disease
Molecular Neurodegeneration Open Access 17 August 2022
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Raw sequencing data (FASTQ files), alignment files (BAM files), TPM data and counts for each sample are available at the LONI IDA. (https://fairsharing.org/, IDA; LONI IDA, https://doi.org/10.25504/FAIRsharing.r4ph5f). Data are also available through the AMP PD (https://amp-pd.org/). These are the requirements for downloading from the AMP PD: (1) personal and institutional or company details; (2) description of intended data use, for example, proposed analyses; (3) institutional signature on the AMP PD Data Use Agreement (for researchers requesting access to individual-level, ’omics data). Additional data, including but not limited to study arm, motor assessments, DaTscan and MRI imaging, genetic testing results, whole-exome and genome sequencing data, patient history and standardized techniques and protocols for data collection are also available through the IDA. To access complete data, researchers need to fill out a data-use agreement. Data are available in a public (institutional, general or participant-specific) repository that does not issue datasets with DOIs (non-mandated deposition).
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This research was supported and funded by the MJFF under grant numbers 12749 (K.V.K.-J.), 12749.01 (K.V.K.-J., M.R.C.) and 14696 (K.V.K.-J., A.K., D.W.C.). Many MJFF staff assisted in harmonizing and transferring data. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. Data used in the preparation of this article were obtained from the PPMI database (https://www.ppmi-info.org/data). For up-to-date information on the study, visit https://www.ppmi-info.org/. We also acknowledge industry partners of the PPMI: AbbVie, Allergan, Amathus Therapeutics, Avid Radiopharmaceuticals, Biogen, BioLegend, Bristol Myers Squibb, Celgene, Denali, GE Healthcare, Genentech, GlaxoSmithKline, Golub Capital, Handl Therapeutics, Insitro, Janssen Neuroscience, Lilly, Lundbeck, Merck, Meso Scale Discovery, Neurocrine Biosciences, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily and Voyager Therapeutics. We also thank the AMP PD for allowing us access to PDBP data. The PDBP consortium is supported by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. A full list of PDBP investigators can be found at https://pdbp.ninds.nih.gov/policy. PDBP investigators have not participated in reviewing the data analysis or content of the text. Data used in the preparation of this article were obtained from the AMP PD Knowledge Platform. For up-to-date information on the study, visit https://www.amp-pd.org. The AMP PD, a public–private partnership, is managed by the FNIH and funded by Celgene, GlaxoSmithKline, the MJFF, the National Institute of Neurological Disorders and Stroke, Pfizer, Sanofi and Verily. We thank all people with PD and families for participating in the study and donating their samples and time. We would like to thank the group at IU for RNA isolation, QC metrics and safe shipment of samples. We thank the group at the HAIB for running sequencing and sample tracking.
B.C., S.H., A.R. and M.F. are employees of the MJFF. E.H., D.W.C., I.V., E.A., K.L.C., A.W.T. and K.V.K.-J. are funded by the MJFF. The other authors declare no competing interests.
Peer review information Nature Aging thanks the anonymous reviewers for their contribution to the peer review of this work.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Craig, D.W., Hutchins, E., Violich, I. et al. RNA sequencing of whole blood reveals early alterations in immune cells and gene expression in Parkinson’s disease. Nat Aging 1, 734–747 (2021). https://doi.org/10.1038/s43587-021-00088-6
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