School of Medicine Publications
Document Type
Article
Publication Date
11-28-2025
Abstract
Genetic variants influencing gene expression have been extensively studied at the transcriptional level. How these variants affect downstream processes remains unclear. We quantitated ribosome occupancy in prefrontal cortex samples from the BrainGVEX cohort and integrated these data with transcriptomic and proteomic profiles from the same individuals. Through cis-QTL mapping, we identified genetic variants associated with transcript level (eQTLs), ribosome occupancy (rQTLs), and protein level (pQTLs). Notably, only 34% of eQTLs have their effects propagated to the protein levels, suggesting widespread post-transcriptional attenuation. Using both a gene-based approach and a variant-based approach we identified omics-specific QTLs that associated with brain disorder GWAS signals and found the majority of them to be driven predominantly by transcriptional regulation. Consistently, using a TWAS approach, we identified 74 SCZ risk genes across the three omics layers, 52 were discovered using transcriptome with 68% showing limited impact on protein expression. Our findings indicated that many disease-associated variants act through regulatory mechanisms that do not lead to an observable impact on the protein level.
Recommended Citation
Liang, Q., Jiang, Y., Shieh, A. W., Zhou, D., Chen, R., Wang, F., ... & Wang, S. H. (2025). Impact of common variants on brain gene expression from RNA to protein to schizophrenia risk. Nature Communications, 16(1), 10773. https://doi.org/10.1038/s41467-025-65818-5
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Publication Title
Nature Communications
DOI
10.1038/s41467-025-65818-5
Academic Level
resident
Mentor/PI Department
Psychiatry
Comments
This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it.