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36/100

✓ Peer-reviewed alzhub usefulness score 36 out of 100. Genetics

Topic: Brain proteins, microglia and lab models

Genome-wide association studies (GWASs) have identified thousands of putative disease-causing variants with unknown regulatory effects. Efforts to connect these variants with splicing quantitative trait loci (sQTLs) have provided functional insights, yet sQTLs reported by existing methods cannot explain many GWAS signals. We show that current sQTL modeling approaches can be improved by considering alternative splicing representation, model calibration, and covariate integration. We then introduce MAJIQTL, a pipeline for sQTL discovery. MAJIQTL includes two statistical methods: a weighted multiple-testing approach for sGene discovery and a model for sQTL effect-size inference to improve variant prioritization. By applying MAJIQTL to GTEx, we find significantly more sGenes harboring sQTLs with functional significance. Notably, our analysis implicates the variant rs528823 in Alzheimer disease. Using antisense oligonucleotides, we test this variant's effect by blocking the implicated YBX3 binding site, leading to exon skipping in MS4A3.

Key findings

By applying MAJIQTL to GTEx, we find significantly more sGenes harboring sQTLs with functional significance.

Why it matters

This study introduced a pipeline for discovering splicing quantitative trait loci and applied it to identify significantly more sGenes with functional significance. The analysis implicated the variant rs528823 in Alzheimer disease, and antisense oligonucleotides blocking the implicated YBX3 binding site led to exon skipping in MS4A3.

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Study details

Evidence strengthLow

How this study scored 36/100

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.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (The American Journal of Human Genetics)
Journal's citation record	3 / 4	The American Journal of Human Genetics: journal h-index 385 (OpenAlex, 2026-10-29)
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	1 / 7	Cited 2 times (OpenAlex, 2026-10-10)
Citations per year	0 / 5	0.7 citations a year over 3 year(s) since 2025
Impact for its field and year	1 / 6	Cited 0.5× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	0 / 6	No other study in this library cites it
Still being cited	0 / 4	Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	2 / 4	Last-listed author Yoseph Barash: h-index 36 (OpenAlex, whole career)
Institution's track record	2 / 3	University of Pennsylvania: institution h-index 1,859 (OpenAlex)
Multi-centre collaboration	1 / 3	OpenAlex lists 2 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 41232530)
Free to read	2 / 2	Free to read
Total	36 / 100	—

What each of these 20 components measures, and what this score is not →

Read the original

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.

APA 7th

Wang, D., Gazzara, M. R., Jewell, S., Wales-McGrath, B. D., Yang, K., Brown, C. D., et al. (2025). A deep dive into statistical modeling of RNA splicing QTLs reveals variants that explain neurodegenerative disease. The American Journal of Human Genetics. https://doi.org/10.1016/j.ajhg.2025.10.012

Vancouver

Wang D, Gazzara MR, Jewell S, Wales-McGrath BD, Yang K, Brown CD, et al. A deep dive into statistical modeling of RNA splicing QTLs reveals variants that explain neurodegenerative disease. The American Journal of Human Genetics. 2025. doi:10.1016/j.ajhg.2025.10.012. PMID: 41232530.

BibTeX

@article{wang2025-41232530,
  author  = {Wang, David and Gazzara, Matthew R. and Jewell, San and Wales-McGrath, Benjamin D and Yang, Kevin and Brown, Christopher D. and Choi, Peter S. and Barash, Yoseph},
  title   = {{A deep dive into statistical modeling of RNA splicing QTLs reveals variants that explain neurodegenerative disease}},
  journal = {The American Journal of Human Genetics},
  year    = {2025},
  doi     = {10.1016/j.ajhg.2025.10.012},
  pmid    = {41232530},
  url     = {https://doi.org/10.1016/j.ajhg.2025.10.012}
}

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