Functional regulatory variants implicate distinct transcriptional networks in dementia
Cooper YA, Teyssier N, Dräger NM, Guo Q, Davis JE, Sattler SM, Yang Z, Patel A et al.. Science (New York, N.Y.), 2022-08-19
Topic: Brain proteins, microglia and lab models
Predicting the function of noncoding variation is a major challenge in modern genetics. In this study, we used massively parallel reporter assays to screen 5706 variants identified from genome-wide association studies for both Alzheimer's disease (AD) and progressive supranuclear palsy (PSP), identifying 320 functional regulatory variants (frVars) across 27 loci, including the complex 17q21.31 region. We identified and validated multiple risk loci using CRISPR interference or excision, including complement 4 ( C4A ) and APOC1 in AD and PLEKHM1 and KANSL1 in PSP. Functional variants disrupt transcription factor binding sites converging on enhancers with cell type-specific activity in PSP and AD, implicating a neuronal SP1-driven regulatory network in PSP pathogenesis. These analyses suggest that noncoding genetic risk is driven by common genetic variants through their aggregate activity on specific transcriptional programs.
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APA 7th
Cooper, Y. A., Teyssier, N., Dräger, N. M., Guo, Q., Davis, J. E., Sattler, S. M., et al. (2022). Functional regulatory variants implicate distinct transcriptional networks in dementia. Science (New York, N.Y.). https://doi.org/10.1126/science.abi8654
Vancouver
Cooper YA, Teyssier N, Dräger NM, Guo Q, Davis JE, Sattler SM, et al. Functional regulatory variants implicate distinct transcriptional networks in dementia. Science (New York, N.Y.). 2022. doi:10.1126/science.abi8654. PMID: 35981026.
BibTeX
@article{cooper2022-35981026,
author = {Cooper, Y. A. and Teyssier, N. and Dräger, N. M. and Guo, Q. and Davis, J. E. and Sattler, S. M. and Yang, Z. and Patel, A. and others},
title = {{Functional regulatory variants implicate distinct transcriptional networks in dementia}},
journal = {Science (New York, N.Y.)},
year = {2022},
doi = {10.1126/science.abi8654},
pmid = {35981026},
url = {https://doi.org/10.1126/science.abi8654}
}
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Key findings
- These analyses suggest that noncoding genetic risk is driven by common genetic variants through their aggregate activity on specific transcriptional programs.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a top-tier 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 and multi-centre collaboration, so those were left out: it earned 26 of the 58 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Science (New York, N.Y.)) |
| 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 | 3 / 5 | 2022 — 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 | — / 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 35981026) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 26 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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