Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: A case-control study
Steele NZ, Carr JS, Bonham LW, Geier EG, Damotte V, Miller ZA, Desikan RS, Boehme KL et al.. PLoS medicine, 2017-03-28
Topic: Amyloid, tau and blood-test diagnosis
Secondary analysis suggested that this effect may be driven primarily by individuals who are negative for the established AD genetic risk factor, apolipoprotein E (APOE) ɛ4. We followed up these findings in the clinical dataset representing the spectrum of cognitively normal controls, individuals with mild cognitive impairment, and individuals with AD to assess their relevance to disease. Carrying A*03:01~B*07:02 was associated with higher CSF amyloid levels (p = 0.03, β ± standard error = 47.19 ± 21.78). In a subset of the same cohort, dose of DR15 was also associated with higher baseline levels of chemokine CC-4, a biomarker of inflammation (p = 0.005, β ± standard error = 0.08 ± 0.03). The main study limitations are that the results represent only individuals of European-ancestry and clinically diagnosed individuals, and that our study used imputed genotypes for a subset of HLA genes. DR15 has also been associated with multiple sclerosis, and its component alleles have been implicated in Parkinson disease and narcolepsy. Our findings thus raise the possibility that DR15-associated mechanisms may contribute to pan-neuronal disease vulnerability.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Steele, N. Z., Carr, J. S., Bonham, L. W., Geier, E. G., Damotte, V., Miller, Z. A., et al. (2017). Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: A case-control study. PLoS medicine. https://doi.org/10.1371/journal.pmed.1002272
Vancouver
Steele NZ, Carr JS, Bonham LW, Geier EG, Damotte V, Miller ZA, et al. Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: A case-control study. PLoS medicine. 2017. doi:10.1371/journal.pmed.1002272. PMID: 28350795.
BibTeX
@article{steele2017-28350795,
author = {Steele, N. Z. and Carr, J. S. and Bonham, L. W. and Geier, E. G. and Damotte, V. and Miller, Z. A. and Desikan, R. S. and Boehme, K. L. and others},
title = {{Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: A case-control study}},
journal = {PLoS medicine},
year = {2017},
doi = {10.1371/journal.pmed.1002272},
pmid = {28350795},
url = {https://doi.org/10.1371/journal.pmed.1002272}
}
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.
Key findings
- Secondary analysis suggested that this effect may be driven primarily by individuals who are negative for the established AD genetic risk factor, apolipoprotein E (APOE) ɛ4.
- We followed up these findings in the clinical dataset representing the spectrum of cognitively normal controls, individuals with mild cognitive impairment, and individuals with AD to assess their relevance to disease.
- Carrying A*03:01~B*07:02 was associated with higher CSF amyloid levels (p = 0.03, β ± standard error = 47.19 ± 21.78).
- In a subset of the same cohort, dose of DR15 was also associated with higher baseline levels of chemokine CC-4, a biomarker of inflammation (p = 0.005, β ± standard error = 0.08 ± 0.03).
- The main study limitations are that the results represent only individuals of European-ancestry and clinically diagnosed individuals, and that our study used imputed genotypes for a subset of HLA genes.
Why it matters
Certain HLA gene variants were associated with higher spinal fluid amyloid levels and, in a subset, with a marker of inflammation, possibly mainly in people without the APOE ε4 risk factor. This is a case-control genetic study and does not test treatment or prevention.
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Study details
- Study designcase-control study
- Participants346
- Effect sizeOR = 1.11; OR = 1.08; or = 47.19
- Evidence strengthModerate
How this study scored 64/100
Published in a peer-reviewed journal, and it is a case-control study. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (PLoS medicine) |
| Journal's citation record | 3 / 4 | PLoS Medicine: journal h-index 350 (OpenAlex, 2026-10-29) |
| 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 | 2 / 5 | 2017 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 346 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 4 / 7 | Cited 91 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.3 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 3 / 6 | Cited 4.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 26 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jennifer S. Yokoyama: h-index 49 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28350795) |
| Free to read | 2 / 2 | Free to read |
| Total | 64 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1371/journal.pmed.1002272
- PubMed: 28350795
- Original source →
- Free full text: PLoS Medicine →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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