Transcription Factor-Wide Association Studies to Identify Functional SNPs in Alzheimer's Disease
Jessica Dunn, Cedric Moore, Nam-Shik Kim, Tianshun Gao, Zhiqiang Cheng, Peng Jin, Guo-Li Ming, Jiang Qian et al.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2025-01-08
Topic: Genetics and APOE
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with profound global impact. While genome-wide association studies (GWAS) have revealed genomic variants linked to AD, their translational impact has been limited due to challenges in interpreting the identified genetic associations. To address this challenge, we have devised a novel approach termed transcription factor-wide association studies (TF-WAS). By integrating the GWAS, expression quantitative trait loci, and transcriptome analyses, we selected 30 AD single nucleotide polymorphisms (SNPs) in noncoding regions that are likely to be functional. Using human transcription factor (TF) microarrays, we have identified 90 allele-specific TF interactions with 53 unique TFs. We then focused on several interactions involving SMAD4 and further validated them using electrophoretic mobility shift assay, luciferase, and chromatin immunoprecipitation on engineered genetic backgrounds (female cells). This approach holds promise for unraveling the intricacies of not just AD, but any complex disease with available GWAS data, providing insight into underlying molecular mechanisms and clues toward potential therapeutic targets.
Key findings
- While genome-wide association studies (GWAS) have revealed genomic variants linked to AD, their translational impact has been limited due to challenges in interpreting the identified genetic associations.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people 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 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| 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 | 2025 — within 3 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 | — / 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 39622643) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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APA 7th
Dunn, J., Moore, C., Kim, N.-S., Gao, T., Cheng, Z., Jin, P., et al. (2025). Transcription Factor-Wide Association Studies to Identify Functional SNPs in Alzheimer's Disease. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.1800-24.2024
Vancouver
Dunn J, Moore C, Kim N.-S, Gao T, Cheng Z, Jin P, et al. Transcription Factor-Wide Association Studies to Identify Functional SNPs in Alzheimer's Disease. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2025. doi:10.1523/jneurosci.1800-24.2024. PMID: 39622643.
BibTeX
@article{dunn2025-39622643,
author = {Dunn, Jessica and Moore, Cedric and Kim, Nam-Shik and Gao, Tianshun and Cheng, Zhiqiang and Jin, Peng and Ming, Guo-Li and Qian, Jiang and others},
title = {{Transcription Factor-Wide Association Studies to Identify Functional SNPs in Alzheimer's Disease}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2025},
doi = {10.1523/jneurosci.1800-24.2024},
pmid = {39622643},
url = {https://doi.org/10.1523/jneurosci.1800-24.2024}
}
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