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Functional characterization of Alzheimer's disease genetic variants in microglia
Yang X, Wen J, Yang H, Jones IR, Zhu X, Liu W, Li B, Clelland CD et al.. Nature genetics, 2023-09-21
Topic: Amyloid, tau and blood-test diagnosis
Candidate cis-regulatory elements (cCREs) in microglia demonstrate the most substantial enrichment for Alzheimer's disease (AD) heritability compared to other brain cell types. However, whether and how these genome-wide association studies (GWAS) variants contribute to AD remain elusive. Here we prioritize 308 previously unreported AD risk variants at 181 cCREs by integrating genetic information with microglia-specific 3D epigenome annotation.
Key findings
- However, whether and how these genome-wide association studies (GWAS) variants contribute to AD remain elusive.
- Here we prioritize 308 previously unreported AD risk variants at 181 cCREs by integrating genetic information with microglia-specific 3D epigenome annotation.
- We further establish the link between functional variants and target genes by single-cell CRISPRi screening in microglia.
- In addition, we show that AD variants exhibit allelic imbalance on target gene expression.
Why it matters
By combining genetic data with microglia-specific 3D genome maps, researchers identified 308 previously unreported Alzheimer's risk variants at 181 regulatory elements and linked some to target genes. This expands understanding of how genetic risk acts through microglia, but it is a genetic mapping study, not a treatment or prevention trial.
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Study details
- Evidence strengthLow
How this study scored 52/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people 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 | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| 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 | 4 / 7 | Cited 72 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.4 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 4 / 6 | Cited 10.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 3 / 4 | Cited 68 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Yin Shen: h-index 26 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37735198) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 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
Yang, X., Wen, J., Yang, H., Jones, I. R., Zhu, X., Liu, W., et al. (2023). Functional characterization of Alzheimer's disease genetic variants in microglia. Nature genetics. https://doi.org/10.1038/s41588-023-01506-8
Vancouver
Yang X, Wen J, Yang H, Jones IR, Zhu X, Liu W, et al. Functional characterization of Alzheimer's disease genetic variants in microglia. Nature genetics. 2023. doi:10.1038/s41588-023-01506-8. PMID: 37735198.
BibTeX
@article{yang2023-37735198,
author = {Yang, X. and Wen, J. and Yang, H. and Jones, I. R. and Zhu, X. and Liu, W. and Li, B. and Clelland, C. D. and others},
title = {{Functional characterization of Alzheimer's disease genetic variants in microglia}},
journal = {Nature genetics},
year = {2023},
doi = {10.1038/s41588-023-01506-8},
pmid = {37735198},
url = {https://doi.org/10.1038/s41588-023-01506-8}
}
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