TY - JOUR
T1 - Analysis of blood-based gene expression in idiopathic Parkinson disease
AU - Shamir, Ron
AU - Klein, Christine
AU - Amar, David
AU - Vollstedt, Eva Juliane
AU - Bonin, Michael
AU - Usenovic, Marija
AU - Wong, Yvette C.
AU - Maver, Ales
AU - Poths, Sven
AU - Safer, Hershel
AU - Corvol, Jean Christophe
AU - Lesage, Suzanne
AU - Lavi, Ofer
AU - Deuschl, Günther
AU - Kuhlenbaeumer, Gregor
AU - Pawlack, Heike
AU - Ulitsky, Igor
AU - Kasten, Meike
AU - Riess, Olaf
AU - Brice, Alexis
AU - Peterlin, Borut
AU - Krainc, Dimitri
PY - 2017/10/17
Y1 - 2017/10/17
N2 - Objective: To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples). Methods: Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks. Results: A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was identified with the training cohort and successfully replicated in both an independent validation cohort (area under the curve [AUC] = 0.79, p = 7.13E-6) and a subsequent independent test cohort (AUC = 0.74, p = 4.2E-4). Network analysis of the signature revealed gene enrichment in pathways, including metabolism, oxidation, and ubiquitination/proteasomal activity, and misregulation of mitochondria-localized genes, including downregulation of COX4I1, ATP5A1, and VDAC3. Conclusions: We present a large-scale study of PD gene expression profiling. This work identifies a reliable blood-based PD signature and highlights the importance of large-scale patient cohorts in developing potential PD biomarkers.
AB - Objective: To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples). Methods: Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks. Results: A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was identified with the training cohort and successfully replicated in both an independent validation cohort (area under the curve [AUC] = 0.79, p = 7.13E-6) and a subsequent independent test cohort (AUC = 0.74, p = 4.2E-4). Network analysis of the signature revealed gene enrichment in pathways, including metabolism, oxidation, and ubiquitination/proteasomal activity, and misregulation of mitochondria-localized genes, including downregulation of COX4I1, ATP5A1, and VDAC3. Conclusions: We present a large-scale study of PD gene expression profiling. This work identifies a reliable blood-based PD signature and highlights the importance of large-scale patient cohorts in developing potential PD biomarkers.
UR - http://www.scopus.com/inward/record.url?scp=85031402930&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000004516
DO - 10.1212/WNL.0000000000004516
M3 - Journal articles
C2 - 28916538
AN - SCOPUS:85031402930
SN - 0028-3878
VL - 89
SP - 1676
EP - 1683
JO - Neurology
JF - Neurology
IS - 16
ER -