Integrating whole-genome sequencing with multi-omic data reveals the impact of structural variants on gene regulation in the human brain
Vialle RA, de Paiva Lopes K, Bennett DA, Crary JF, Raj T.. Nature neuroscience, 2022-03-14
Topic: Brain proteins, microglia and lab models
Structural variants (SVs), which are genomic rearrangements of more than 50 base pairs, are an important source of genetic diversity and have been linked to many diseases. However, it remains unclear how they modulate human brain function and disease risk. Here we report 170,996 SVs discovered using 1,760 short-read whole genomes from aged adults and individuals with Alzheimer's disease. By applying quantitative trait locus (SV-xQTL) analyses, we quantified the impact of cis-acting SVs on histone modifications, gene expression, splicing and protein abundance in postmortem brain tissues. More than 3,200 SVs were associated with at least one molecular phenotype. We found reproducibility of 65-99% SV-eQTLs across cohorts and brain regions. SV associations with mRNA and proteins shared the same direction of effect in more than 87% of SV-gene pairs. Mediation analysis showed ~8% of SV-eQTLs mediated by histone acetylation and ~11% by splicing. Additionally, associations of SVs with progressive supranuclear palsy identified previously known and novel SVs.
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APA 7th
Vialle, R. A., de Paiva Lopes, K., Bennett, D. A., Crary, J. F., & Raj, T. (2022). Integrating whole-genome sequencing with multi-omic data reveals the impact of structural variants on gene regulation in the human brain. Nature neuroscience. https://doi.org/10.1038/s41593-022-01031-7
Vancouver
Vialle RA, de Paiva Lopes K, Bennett DA, Crary JF, Raj T. Integrating whole-genome sequencing with multi-omic data reveals the impact of structural variants on gene regulation in the human brain. Nature neuroscience. 2022. doi:10.1038/s41593-022-01031-7. PMID: 35288716.
BibTeX
@article{vialle2022-35288716,
author = {Vialle, R. A. and de Paiva Lopes, K. and Bennett, D. A. and Crary, J. F. and Raj, T.},
title = {{Integrating whole-genome sequencing with multi-omic data reveals the impact of structural variants on gene regulation in the human brain}},
journal = {Nature neuroscience},
year = {2022},
doi = {10.1038/s41593-022-01031-7},
pmid = {35288716},
url = {https://doi.org/10.1038/s41593-022-01031-7}
}
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Key findings
- More than 3,200 SVs were associated with at least one molecular phenotype.
- We found reproducibility of 65-99% SV-eQTLs across cohorts and brain regions.
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Study details
- Evidence strengthLow
How this study scored 47/100
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 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature 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 | 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 35288716) |
| Free to read | 2 / 2 | Free to read |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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