Cell subtype-specific effects of genetic variation in the Alzheimer's disease brain
Fujita M, Gao Z, Zeng L, McCabe C, White CC, Ng B, Green GS, Rozenblatt-Rosen O et al.. Nature genetics, 2024-03-21
Topic: Genetics and APOE
The relationship between genetic variation and gene expression in brain cell types and subtypes remains understudied. Here, we generated single-nucleus RNA sequencing data from the neocortex of 424 individuals of advanced age; we assessed the effect of genetic variants on RNA expression in cis (cis-expression quantitative trait loci) for seven cell types and 64 cell subtypes using 1.5 million transcriptomes. This effort identified 10,004 eGenes at the cell type level and 8,099 eGenes at the cell subtype level. Many eGenes are only detected within cell subtypes. A new variant influences APOE expression only in microglia and is associated with greater cerebral amyloid angiopathy but not Alzheimer's disease pathology, after adjusting for APOEε4, providing mechanistic insights into both pathologies. Furthermore, only a TMEM106B variant affects the proportion of cell subtypes. Integration of these results with genome-wide association studies highlighted the targeted cell type and probable causal gene within Alzheimer's disease, schizophrenia, educational attainment and Parkinson's disease loci.
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APA 7th
Fujita, M., Gao, Z., Zeng, L., McCabe, C., White, C. C., Ng, B., et al. (2024). Cell subtype-specific effects of genetic variation in the Alzheimer's disease brain. Nature genetics. https://doi.org/10.1038/s41588-024-01685-y
Vancouver
Fujita M, Gao Z, Zeng L, McCabe C, White CC, Ng B, et al. Cell subtype-specific effects of genetic variation in the Alzheimer's disease brain. Nature genetics. 2024. doi:10.1038/s41588-024-01685-y. PMID: 38514782.
BibTeX
@article{fujita2024-38514782,
author = {Fujita, M. and Gao, Z. and Zeng, L. and McCabe, C. and White, C. C. and Ng, B. and Green, G. S. and Rozenblatt-Rosen, O. and others},
title = {{Cell subtype-specific effects of genetic variation in the Alzheimer's disease brain}},
journal = {Nature genetics},
year = {2024},
doi = {10.1038/s41588-024-01685-y},
pmid = {38514782},
url = {https://doi.org/10.1038/s41588-024-01685-y}
}
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Key findings
- A new variant influences APOE expression only in microglia and is associated with greater cerebral amyloid angiopathy but not Alzheimer's disease pathology, after adjusting for APOEε4, providing mechanistic insights into both pathologies.
- Integration of these results with genome-wide association studies highlighted the targeted cell type and probable causal gene within Alzheimer's disease, schizophrenia, educational attainment and Parkinson's disease loci.
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Study details
- Participants424
- Evidence strengthLow
How this study scored 53/100
Published in a leading specialty 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 and multi-centre collaboration, so those were left out: it earned 31 of the 58 points we could judge it on, which is 53 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature genetics) |
| 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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 424 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 38514782) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 31 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 31 of the 58 points we could judge it on is 53 out of 100. |
| Total | 53 / 100 | — |
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