# Genetic modulation of protein expression in rat brain

## TL;DR

This study explores how genetic differences affect protein expression in rat brains, linking these changes to complex traits and human diseases.

## Contribution

The study provides a large-scale proteo-genetic dataset in rats, revealing sex-specific and translatable pQTLs linked to CNS traits.

## Key findings

- Quantified 8,119 proteins and identified 597 differentially expressed proteins in rat brain proteomes.
- Discovered 464 proteins linked to cis-acting pQTLs and 95 variant peptides through proteogenomics.
- Found sex-specific pQTLs and connections between rat pQTLs and human disorders.

## Abstract

Genetic variations in protein expression are implicated in a broad spectrum of common diseases and complex traits but remain less explored compared to mRNA and classical phenotypes. This study systematically analyzed brain proteomes in a rat family using tandem mass tag (TMT)-based quantitative mass spectrometry. We quantified 8,119 proteins across two parental strains (SHR/Olalpcv and BN-Lx/Cub) and 29 HXB/BXH recombinant inbred (RI) strains, identifying 597 proteins with differential expression and 464 proteins linked to cis-acting quantitative trait loci (pQTLs). Proteogenomics identified 95 variant peptides, and sex-specific analyses revealed both shared and distinct cis-pQTLs. We improved the ability to pinpoint candidate genes underlying pQTLs by utilizing the rat pangenome and explored the connections between pQTLs in rats and human disorders. Collectively, this study highlights the value of large proteo-genetic datasets in elucidating protein modulation in the brain and its links to complex central nervous system (CNS) traits.

•Profiling rat brain proteome reveals genetic regulation of protein expression•Integrating proteome and phenotypic data links protein expression to complex traits in rats•Identifying sex-specific pQTLs uncovers distinct protein regulations between sexes•Linking rat pQTLs to human disorders highlights the translational potential

Profiling rat brain proteome reveals genetic regulation of protein expression

Integrating proteome and phenotypic data links protein expression to complex traits in rats

Identifying sex-specific pQTLs uncovers distinct protein regulations between sexes

Linking rat pQTLs to human disorders highlights the translational potential

Biochemistry; Genetics; Neuroscience