Chromatin activity at GWAS loci identifies T cell states driving complex immune diseases
Soskic B, Cano-Gamez K, Smyth DJ, Rowan WC, Nakic N, Esparza-Gordillo J, Bossini-Castillo L, Tough DF et al.. Nature genetics, 2019-09-23
Topic: Brain proteins, microglia and lab models
Immune-disease-associated variants are enriched in active chromatin regions of T cells and macrophages. However, whether these variants function in specific cell states is unknown. Here we stimulated T cells and macrophages in the presence of 13 cytokines and profiled active and open chromatin regions. T cell activation induced major chromatin remodeling, while the presence of cytokines fine-tuned the magnitude of changes. We developed a statistical method that accounts for subtle changes in the chromatin landscape to identify SNP enrichment across cell states. Our results point towards the role of immune-disease-associated variants in early rather than late activation of memory CD4 + T cells, with modest differences across cytokines. Furthermore, variants associated with inflammatory bowel disease are enriched in type 1 T helper (T H 1) cells, whereas variants associated with Alzheimer's disease are enriched in different macrophage cell states. Our results represent an in-depth analysis of immune-disease-associated variants across a comprehensive panel of activation states of T cells and macrophages.
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APA 7th
Soskic, B., Cano-Gamez, K., Smyth, D. J., Rowan, W. C., Nakic, N., Esparza-Gordillo, J., et al. (2019). Chromatin activity at GWAS loci identifies T cell states driving complex immune diseases. Nature genetics. https://doi.org/10.1038/s41588-019-0493-9
Vancouver
Soskic B, Cano-Gamez K, Smyth DJ, Rowan WC, Nakic N, Esparza-Gordillo J, et al. Chromatin activity at GWAS loci identifies T cell states driving complex immune diseases. Nature genetics. 2019. doi:10.1038/s41588-019-0493-9. PMID: 31548716.
BibTeX
@article{soskic2019-31548716,
author = {Soskic, B. and Cano-Gamez, K. and Smyth, D. J. and Rowan, W. C. and Nakic, N. and Esparza-Gordillo, J. and Bossini-Castillo, L. and Tough, D. F. and others},
title = {{Chromatin activity at GWAS loci identifies T cell states driving complex immune diseases}},
journal = {Nature genetics},
year = {2019},
doi = {10.1038/s41588-019-0493-9},
pmid = {31548716},
url = {https://doi.org/10.1038/s41588-019-0493-9}
}
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Key findings
- Our results point towards the role of immune-disease-associated variants in early rather than late activation of memory CD4 + T cells, with modest differences across cytokines.
- Furthermore, variants associated with inflammatory bowel disease are enriched in type 1 T helper (T H 1) cells, whereas variants associated with Alzheimer's disease are enriched in different macrophage cell states.
- Our results represent an in-depth analysis of immune-disease-associated variants across a comprehensive panel of activation states of T cells and macrophages.
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Study details
- Evidence strengthLow
How this study scored 45/100
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. 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 | 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 | 2 / 5 | 2019 — within 10 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 31548716) |
| Free to read | 2 / 2 | Free to read |
| 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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