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A genome-wide association study of plasma phosphorylated tau181
Jodie Lord, Anna Zettergren, Nicholas J Ashton, Thomas K Karikari, Andrea L Benedet, Joel Simrén, Alzheimer's Disease Neuroimaging Initiative, Abdul Hye et al.. Neurobiology of aging, 2021-05-04
Topic: Genetics and APOE
Plasma phosphorylated tau at threonine-181 (P-tau181) demonstrates promise as an accessible blood-based biomarker specific to Alzheimer's Disease (AD), with levels recently demonstrating high predictive accuracy for AD-relevant pathology. The genetic underpinnings of P-tau181 levels, however, remain elusive. This study presents the first genome-wide association study of plasma P-tau181 in a total sample of 1153 participants from 2 independent cohorts. No loci, other than those within the APOE genomic region (lead variant = rs429358, beta = 0.32, p =8.44 × 10-25) demonstrated association with P-tau181 at genome-wide significance (p < 5 × 10-08), though rs60872856 on chromosome 2 came close (beta = -0.28, p = 3.23 × 10-07, nearest gene=CYTIP). As the APOE ε4 allele is already a well-established genetic variant associated with AD, this study found no evidence of novel genetic associations relevant to plasma P-tau181, though presents rs60872856 on chromosome 2 as a candidate locus to be further evaluated in future larger size GWAS.
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APA 7th
Lord, J., Zettergren, A., Ashton, N. J., Karikari, T. K., Benedet, A. L., Simrén, J., et al. (2021). A genome-wide association study of plasma phosphorylated tau181. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2021.04.018
Vancouver
Lord J, Zettergren A, Ashton NJ, Karikari TK, Benedet AL, Simrén J, et al. A genome-wide association study of plasma phosphorylated tau181. Neurobiology of aging. 2021. doi:10.1016/j.neurobiolaging.2021.04.018. PMID: 34119372.
BibTeX
@article{lord2021-34119372,
author = {Lord, Jodie and Zettergren, Anna and Ashton, Nicholas J and Karikari, Thomas K and Benedet, Andrea L and Simrén, Joel and {Alzheimer's Disease Neuroimaging Initiative} and Hye, Abdul and others},
title = {{A genome-wide association study of plasma phosphorylated tau181}},
journal = {Neurobiology of aging},
year = {2021},
doi = {10.1016/j.neurobiolaging.2021.04.018},
pmid = {34119372},
url = {https://doi.org/10.1016/j.neurobiolaging.2021.04.018}
}
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Key findings
- No loci, other than those within the APOE genomic region (lead variant = rs429358, beta = 0.32, p =8.44 × 10-25) demonstrated association with P-tau181 at genome-wide significance (p < 5 × 10-08), though rs60872856 on chromosome 2 came close (beta = -0.28, p = 3.23 × 10-07, nearest gene=CYTIP).
- As the APOE ε4 allele is already a well-established genetic variant associated with AD, this study found no evidence of novel genetic associations relevant to plasma P-tau181, though presents rs60872856 on chromosome 2 as a candidate locus to be further evaluated in future larger size GWAS.
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Study details
- Participants1,153
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported 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, multi-centre collaboration and free to read, so those were left out: it earned 29 of the 56 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,153 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 | — / 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 34119372) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 29 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 29 of the 56 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
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