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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
Van Deerlin VM, Sleiman PM, Martinez-Lage M, Chen-Plotkin A, Wang LS, Graff-Radford NR, Dickson DW, Rademakers R et al.. Nature genetics, 2010-02-14
Topic: Brain proteins, microglia and lab models
Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
Key findings
- We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B.
Why it matters
In a genome-wide association study of 515 people with frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), common DNA variants in a region of chromosome 7p21 containing the gene TMEM106B were linked to the disease (top variant rs1990622, P = 1.08 × 10⁻¹¹), and the link was repeated in a further 89 cases. The authors say their data "implicate variants in TMEM106B as a strong risk factor for FTLD-TDP", and propose that the variants "may" act by increasing TMEM106B expression. This is an inherited genetic association in frontotemporal dementia, not Alzheimer's disease. It does not identify anything a person can change, and it tests no treatment, test or prevention.
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Study details
- Participants515
- Evidence strengthLow
How this study scored 66/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature genetics) |
| Journal's citation record | 4 / 4 | Nature Genetics: journal h-index 776 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 515 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 591 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 32.8 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 5 / 6 | Cited 23.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 43 other studies in this library |
| Still being cited | 3 / 4 | Cited 122 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Virginia M.‐Y. Lee: h-index 202 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 85 institution(s) in 12 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20154673) |
| Free to read | 2 / 2 | Free to read |
| Total | 66 / 100 | — |
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Read the original
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
Van Deerlin, V. M., Sleiman, P. M., Martinez-Lage, M., Chen-Plotkin, A., Wang, L. S., Graff-Radford, N. R., et al. (2010). Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions. Nature genetics. https://doi.org/10.1038/ng.536
Vancouver
Van Deerlin VM, Sleiman PM, Martinez-Lage M, Chen-Plotkin A, Wang LS, Graff-Radford NR, et al. Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions. Nature genetics. 2010. doi:10.1038/ng.536. PMID: 20154673.
BibTeX
@article{vandeerlin2010-20154673,
author = {Van Deerlin, V. M. and Sleiman, P. M. and Martinez-Lage, M. and Chen-Plotkin, A. and Wang, L. S. and Graff-Radford, N. R. and Dickson, D. W. and Rademakers, R. and others},
title = {{Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions}},
journal = {Nature genetics},
year = {2010},
doi = {10.1038/ng.536},
pmid = {20154673},
url = {https://doi.org/10.1038/ng.536}
}
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