| Title |
Shared genetic risk between corticobasal degeneration, progressive supranuclear palsy, and frontotemporal dementia
|
|---|---|
| Published in |
Acta Neuropathologica, March 2017
|
| DOI | 10.1007/s00401-017-1693-y |
| Pubmed ID | |
| Authors |
Jennifer S. Yokoyama, Celeste M. Karch, Chun C. Fan, Luke W. Bonham, Naomi Kouri, Owen A. Ross, Rosa Rademakers, Jungsu Kim, Yunpeng Wang, Günter U. Höglinger, Ulrich Müller, Raffaele Ferrari, John Hardy, International FTD-Genomics Consortium (IFGC), Parastoo Momeni, Leo P. Sugrue, Christopher P. Hess, A. James Barkovich, Adam L. Boxer, William W. Seeley, Gil D. Rabinovici, Howard J. Rosen, Bruce L. Miller, Nicholas J. Schmansky, Bruce Fischl, Bradley T. Hyman, Dennis W. Dickson, Gerard D. Schellenberg, Ole A. Andreassen, Anders M. Dale, Rahul S. Desikan |
| Abstract |
Corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and a subset of frontotemporal dementia (FTD) are neurodegenerative disorders characterized by tau inclusions in neurons and glia (tauopathies). Although clinical, pathological and genetic evidence suggests overlapping pathobiology between CBD, PSP, and FTD, the relationship between these disorders is still not well understood. Using summary statistics (odds ratios and p values) from large genome-wide association studies (total n = 14,286 cases and controls) and recently established genetic methods, we investigated the genetic overlap between CBD and PSP and CBD and FTD. We found up to 800-fold enrichment of genetic risk in CBD across different levels of significance for PSP or FTD. In addition to NSF (tagging the MAPT H1 haplotype), we observed that SNPs in or near MOBP, CXCR4, EGFR, and GLDC showed significant genetic overlap between CBD and PSP, whereas only SNPs tagging the MAPT haplotype overlapped between CBD and FTD. The risk alleles of the shared SNPs were associated with expression changes in cis-genes. Evaluating transcriptome levels across adult human brains, we found a unique neuroanatomic gene expression signature for each of the five overlapping gene loci (omnibus ANOVA p < 2.0 × 10(-16)). Functionally, we found that these shared risk genes were associated with protein interaction and gene co-expression networks and showed enrichment for several neurodevelopmental pathways. Our findings suggest: (1) novel genetic overlap between CBD and PSP beyond the MAPT locus; (2) strong ties between CBD and FTD through the MAPT clade, and (3) unique combinations of overlapping genes that may, in part, influence selective regional or neuronal vulnerability observed in specific tauopathies. |
X Demographics
The data shown below were collected from the profiles of 19 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 9 | 47% |
| Spain | 1 | 5% |
| United Kingdom | 1 | 5% |
| Finland | 1 | 5% |
| Unknown | 7 | 37% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 12 | 63% |
| Scientists | 4 | 21% |
| Practitioners (doctors, other healthcare professionals) | 3 | 16% |
Mendeley readers
The data shown below were compiled from readership statistics for 141 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 141 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 21 | 15% |
| Researcher | 21 | 15% |
| Other | 11 | 8% |
| Student > Bachelor | 11 | 8% |
| Professor | 10 | 7% |
| Other | 30 | 21% |
| Unknown | 37 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 35 | 25% |
| Biochemistry, Genetics and Molecular Biology | 18 | 13% |
| Medicine and Dentistry | 18 | 13% |
| Agricultural and Biological Sciences | 10 | 7% |
| Psychology | 9 | 6% |
| Other | 10 | 7% |
| Unknown | 41 | 29% |
Attention Score in Context
This research output has an Altmetric Attention Score of 40. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 March 2021.
All research outputs
#909,047
of 23,577,654 outputs
Outputs from Acta Neuropathologica
#133
of 2,407 outputs
Outputs of similar age
#20,006
of 309,161 outputs
Outputs of similar age from Acta Neuropathologica
#8
of 33 outputs
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