Gene expression profiles in Parkinson disease prefrontal cortex implicate FOXO1 and genes under its transcriptional regulation
Dumitriu A, Latourelle JC, Hadzi TC, Pankratz N, Garza D, Miller JP, Vance JM, Foroud T et al.. PLoS genetics, 2012-06-28
Topic: Brain proteins, microglia and lab models
Parkinson disease (PD) is a complex neurodegenerative disorder with largely unknown genetic mechanisms. While the degeneration of dopaminergic neurons in PD mainly takes place in the substantia nigra pars compacta (SN) region, other brain areas, including the prefrontal cortex, develop Lewy bodies, the neuropathological hallmark of PD. We generated and analyzed expression data from the prefrontal cortex Brodmann Area 9 (BA9) of 27 PD and 26 control samples using the 44K One-Color Agilent 60-mer Whole Human Genome Microarray. All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR) of 5%. One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1) transcription factor. Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR-significant group of genes (177 genes covered by 189 probes), suggesting a role for FoxO1 upstream of the observed expression changes. Single-nucleotide polymorphisms (SNPs) selected from a recent meta-analysis of PD genome-wide association studies (GWAS) were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression-SNP (eSNP) analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes. A significant association was observed between a SNP in the cyclin G associated kinase (GAK) gene and a probe in the spermine oxidase (SMOX) gene. Further examination of the FOXO1 region in a meta-analysis of six available GWAS showed two SNPs significantly associated with age at onset of PD. These results implicate FOXO1 as a PD-relevant gene and warrant further functional analyses of its transcriptional regulatory mechanisms.
Key findings
- All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR) of 5%.
- One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1) transcription factor.
- Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR-significant group of genes (177 genes covered by 189 probes), suggesting a role for FoxO1 upstream of the observed expression changes.
- Single-nucleotide polymorphisms (SNPs) selected from a recent meta-analysis of PD genome-wide association studies (GWAS) were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression-SNP (eSNP) analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes.
- A significant association was observed between a SNP in the cyclin G associated kinase (GAK) gene and a probe in the spermine oxidase (SMOX) gene.
Why it matters
This study of brain tissue from people with Parkinson disease found altered expression of the FOXO1 gene and related genes, but the samples were selected to have no significant Alzheimer disease pathology. The results are about Parkinson disease and do not provide direct evidence for Alzheimer treatment or prevention.
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Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 62/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (PLoS genetics) |
| Journal's citation record | 3 / 4 | PLoS Genetics: journal h-index 341 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 4 / 7 | Cited 91 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.7 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 3 / 6 | Cited 4.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 20 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Richard H. Myers: h-index 100 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Minnesota: institution h-index 1,568 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22761592) |
| Free to read | 2 / 2 | Free to read |
| Total | 62 / 100 | — |
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Read the original
- DOI: 10.1371/journal.pgen.1002794
- PubMed: 22761592
- Original source →
- Free full text: PLoS Genetics →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Dumitriu, A., Latourelle, J. C., Hadzi, T. C., Pankratz, N., Garza, D., Miller, J. P., et al. (2012). Gene expression profiles in Parkinson disease prefrontal cortex implicate FOXO1 and genes under its transcriptional regulation. PLoS genetics. https://doi.org/10.1371/journal.pgen.1002794
Vancouver
Dumitriu A, Latourelle JC, Hadzi TC, Pankratz N, Garza D, Miller JP, et al. Gene expression profiles in Parkinson disease prefrontal cortex implicate FOXO1 and genes under its transcriptional regulation. PLoS genetics. 2012. doi:10.1371/journal.pgen.1002794. PMID: 22761592.
BibTeX
@article{dumitriu2012-22761592,
author = {Dumitriu, A. and Latourelle, J. C. and Hadzi, T. C. and Pankratz, N. and Garza, D. and Miller, J. P. and Vance, J. M. and Foroud, T. and others},
title = {{Gene expression profiles in Parkinson disease prefrontal cortex implicate FOXO1 and genes under its transcriptional regulation}},
journal = {PLoS genetics},
year = {2012},
doi = {10.1371/journal.pgen.1002794},
pmid = {22761592},
url = {https://doi.org/10.1371/journal.pgen.1002794}
}
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