Language
English
Publication Date
5-8-2025
Journal
Nature Communications
DOI
10.1038/s41467-025-59524-5
PMID
40341583
PMCID
PMC12062405
PubMedCentral® Posted Date
5-8-2025
PubMedCentral® Full Text Version
Post-print
Abstract
24-hour biological rhythms are essential to maintain physiological homeostasis. Disruption of these rhythms increases the risks of multiple diseases. Biological rhythms are known to have a genetic basis formed by core clock genes, but how individual genetic variation shapes the oscillating transcriptome and contributes to human chronophysiology and disease risk is largely unknown. Here, we mapped interactions between temporal gene expression and genotype to identify quantitative trait loci (QTLs) contributing to rhythmic gene expression. These newly identified QTLs were termed as rhythmic QTLs (rhyQTLs), which determine previously unappreciated rhythmic genes in human subpopulations with specific genotypes. Functionally, rhyQTLs and their associated rhythmic genes contribute extensively to essential chronophysiological processes, including bile acid and lipid metabolism. The identification of rhyQTLs sheds light on the genetic mechanisms of gene rhythmicity, offers mechanistic insights into variations in human disease risk, and enables precision chronotherapeutic approaches for patients.
Keywords
Humans, Quantitative Trait Loci, Circadian Rhythm, Genetic Variation, Genetic Predisposition to Disease, Male, Transcriptome, Genotype, Gene Expression Regulation, Female, Polymorphism, Single Nucleotide, Lipid Metabolism, Metabolic diseases, Quantitative trait, Genome-wide association studies
Published Open-Access
yes
Recommended Citation
Chen, Ying; Liu, Panpan; Sabo, Aniko; et al., "Human Genetic Variation Determines 24-Hour Rhythmic Gene Expression and Disease Risk" (2025). Faculty and Staff Publications. 4364.
https://digitalcommons.library.tmc.edu/baylor_docs/4364