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Linkage disequilibrium fine mapping and haplotype association analysis of the tau gene in progressive supranuclear palsy and corticobasal degeneration
Pittman AM, Myers AJ, Abou-Sleiman P, Fung HC, Kaleem M, Marlowe L, Duckworth J, Leung D et al.. Journal of medical genetics, 2005-03-25
Topic: Genetics and APOE
Background The haplotype H1 of the tau gene, MAPT, is highly associated with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Objective To investigate the pathogenic basis of this association. Methods Detailed linkage disequilibrium and common haplotype structure of MAPT were examined in 27 CEPH trios using validated HapMap genotype data for 24 single nucleotide polymorphisms (SNPs) spanning MAPT. Results Multiple variants of the H1 haplotype were resolved, reflecting a far greater diversity of MAPT than can be explained by the H1 and H2 clades alone. Based on this, six haplotype tagging SNPs (htSNPs) that capture 95% of the common haplotype diversity were used to genotype well characterised PSP and CBD case-control cohorts. In addition to strong association with PSP and CBD of individual SNPs, two common haplotypes derived from these htSNPs were identified that are highly associated with PSP: the sole H2 derived haplotype was underrepresented and one of the common H1 derived haplotypes was highly associated, with a similar trend observed in CBD. There were powerful and highly significant associations with PSP and CBD of haplotypes formed by three H1 specific SNPs. This made it possible to define a candidate region of at least approximately 56 kb, spanning sequences from upstream of MAPT exon 1 to intron 9. On the H1 haplotype background, these could harbour the pathogenic variants. Conclusions The findings support the pathological evidence that underlying variations in MAPT could contribute to disease pathogenesis by subtle effects on gene expression and/or splicing. They also form the basis for the investigation of the possible genetic role of MAPT in Parkinson's disease and other tauopathies, including Alzheimer's disease.
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APA 7th
Pittman, A. M., Myers, A. J., Abou-Sleiman, P., Fung, H. C., Kaleem, M., Marlowe, L., et al. (2005). Linkage disequilibrium fine mapping and haplotype association analysis of the tau gene in progressive supranuclear palsy and corticobasal degeneration. Journal of medical genetics. https://doi.org/10.1136/jmg.2005.031377
Vancouver
Pittman AM, Myers AJ, Abou-Sleiman P, Fung HC, Kaleem M, Marlowe L, et al. Linkage disequilibrium fine mapping and haplotype association analysis of the tau gene in progressive supranuclear palsy and corticobasal degeneration. Journal of medical genetics. 2005. doi:10.1136/jmg.2005.031377. PMID: 15792962.
BibTeX
@article{pittman2005-15792962,
author = {Pittman, A. M. and Myers, A. J. and Abou-Sleiman, P. and Fung, H. C. and Kaleem, M. and Marlowe, L. and Duckworth, J. and Leung, D. and others},
title = {{Linkage disequilibrium fine mapping and haplotype association analysis of the tau gene in progressive supranuclear palsy and corticobasal degeneration}},
journal = {Journal of medical genetics},
year = {2005},
doi = {10.1136/jmg.2005.031377},
pmid = {15792962},
url = {https://doi.org/10.1136/jmg.2005.031377}
}
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Key findings
- Background The haplotype H1 of the tau gene, MAPT, is highly associated with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD).
- Results Multiple variants of the H1 haplotype were resolved, reflecting a far greater diversity of MAPT than can be explained by the H1 and H2 clades alone.
- In addition to strong association with PSP and CBD of individual SNPs, two common haplotypes derived from these htSNPs were identified that are highly associated with PSP: the sole H2 derived haplotype was underrepresented and one of the common H1 derived haplotypes was highly associated, with a similar trend observed in CBD.
- There were powerful and highly significant associations with PSP and CBD of haplotypes formed by three H1 specific SNPs.
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Study details
- Study designcase-control study
- Evidence strengthModerate
How this study scored 50/100
Published in a peer-reviewed journal, and it is a case-control study. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 29 of the 58 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of medical genetics) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 6 / 12 | A case-control study |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2005 — older than 20 years, still counted |
| 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 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15792962) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 29 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 29 of the 58 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | — |
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