학술논문
RNA sequencing of whole blood reveals early alterations in immune cells and gene expression in Parkinson's disease.
Document Type
Academic Journal
Author
Craig DW; Institute of Translational Genomics, University of Southern California, Los Angeles, CA, USA.; Hutchins E; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA.; Violich I; Institute of Translational Genomics, University of Southern California, Los Angeles, CA, USA.; Alsop E; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA.; Gibbs JR; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.; Levy S; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.; Robison M; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.; Prasad N; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.; Foroud T; Indiana University, Indianapolis, IN, USA.; Crawford KL; Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.; Toga AW; Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.; Whitsett TG; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA.; Kim S; Center for Computational Systems Biology, Department of Electrical and Computer Engineering, Roy G. Perry College of Engineering, Prairie View A&M University, Prairie View, TX, USA.; Casey B; The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.; Reimer A; The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.; Hutten SJ; The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.; Frasier M; The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.; Kern F; Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.; Fehlman T; Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.; Keller A; Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.; Cookson MR; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.; Van Keuren-Jensen K; Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA. kjensen@tgen.org.
Source
Publisher: Nature Publishing Group US Country of Publication: United States NLM ID: 101773306 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2662-8465 (Electronic) Linking ISSN: 26628465 NLM ISO Abbreviation: Nat Aging Subsets: MEDLINE
Subject
Language
English
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.
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)