The Caribbean-Hispanic Alzheimer's disease brain transcriptome reveals ancestry-specific disease mechanisms
Daniel Felsky, Ismael Santa-Maria, Mehmet Ilyas Cosacak, Leon French, Julie A Schneider, David A Bennett, Philip L De Jager, Caghan Kizil et al.. Neurobiology of disease, 2022-11-30
Topic: Genetics and APOE
Identifying ancestry-specific molecular profiles of late-onset Alzheimer's Disease (LOAD) in brain tissue is crucial to understand novel mechanisms and develop effective interventions in non-European, high-risk populations. We performed gene differential expression (DE) and consensus network-based analyses in RNA-sequencing data of postmortem brain tissue from 39 Caribbean Hispanics (CH). To identify ancestry-concordant and -discordant expression profiles, we compared our results to those from two independent non-Hispanic White (NHW) samples (n = 731). In CH, we identified 2802 significant DE genes, including several LOAD known-loci. DE effects were highly concordant across ethnicities, with 373 genes transcriptome-wide significant in all three cohorts. Cross-ancestry meta-analysis found NPNT to be the top DE gene. We replicated over 82% of meta-analyses genome-wide signals in single-nucleus RNA-seq data (including NPNT and LOAD known-genes SORL1, FBXL7, CLU, ABCA7). Increasing representation in genetic studies will allow for deeper understanding of ancestry-specific mechanisms and improving precision treatment options in understudied groups.
Key findings
- To identify ancestry-concordant and -discordant expression profiles, we compared our results to those from two independent non-Hispanic White (NHW) samples (n = 731).
- In CH, we identified 2802 significant DE genes, including several LOAD known-loci.
- DE effects were highly concordant across ethnicities, with 373 genes transcriptome-wide significant in all three cohorts.
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Study details
- Study designmeta-analysis
- Participants731
- Evidence strengthHigh
How this study scored 79/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported 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 44 of the 56 points we could judge it on, which is 79 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of disease) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” 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 | 2 / 4 | 731 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 | A review of other studies — randomisation is not credited here |
| 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 36462719) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 44 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 44 of the 56 points we could judge it on is 79 out of 100. |
| Total | 79 / 100 | — |
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APA 7th
Felsky, D., Santa-Maria, I., Cosacak, M. I., French, L., Schneider, J. A., Bennett, D. A., et al. (2023). The Caribbean-Hispanic Alzheimer's disease brain transcriptome reveals ancestry-specific disease mechanisms. Neurobiology of disease. https://doi.org/10.1016/j.nbd.2022.105938
Vancouver
Felsky D, Santa-Maria I, Cosacak MI, French L, Schneider JA, Bennett DA, et al. The Caribbean-Hispanic Alzheimer's disease brain transcriptome reveals ancestry-specific disease mechanisms. Neurobiology of disease. 2023. doi:10.1016/j.nbd.2022.105938. PMID: 36462719.
BibTeX
@article{felsky2023-36462719,
author = {Felsky, Daniel and Santa-Maria, Ismael and Cosacak, Mehmet Ilyas and French, Leon and Schneider, Julie A and Bennett, David A and De Jager, Philip L and Kizil, Caghan and others},
title = {{The Caribbean-Hispanic Alzheimer's disease brain transcriptome reveals ancestry-specific disease mechanisms}},
journal = {Neurobiology of disease},
year = {2023},
doi = {10.1016/j.nbd.2022.105938},
pmid = {36462719},
url = {https://doi.org/10.1016/j.nbd.2022.105938}
}