Human genetic variation determines 24-hour rhythmic gene expression and disease risk

作者：Ying Chen, Panpan Liu, Aniko Sabo, Dongyin Guan · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-59524-5 · 被引用次数：6 · 研究领域：Circadian rhythm and melatonin、Dietary Effects on Health、Obesity, Physical Activity, Diet

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. Circadian rhythms influence key physiological functions. Here, the authors defined rhythmic quantitative trait loci that reveal novel genotype-specific rhythmic genes, explaining individual variations in rhythmic gene expression and disease risk.