Chen Ying, Liu Panpan, Sabo Aniko, Guan Dongyin
Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Nat Commun. 2025 May 8;16(1):4270. doi: 10.1038/s41467-025-59524-5.
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.
24小时生物节律对于维持生理稳态至关重要。这些节律的紊乱会增加多种疾病的风险。已知生物节律具有由核心时钟基因形成的遗传基础，但个体遗传变异如何塑造振荡转录组并影响人类时间生理学和疾病风险在很大程度上尚不清楚。在这里，我们绘制了时间基因表达与基因型之间的相互作用，以确定有助于节律性基因表达的数量性状位点（QTL）。这些新鉴定的QTL被称为节律性QTL（rhyQTL），它们在具有特定基因型的人类亚群中决定了以前未被认识到的节律性基因。在功能上，rhyQTL及其相关的节律性基因广泛参与基本的时间生理过程，包括胆汁酸和脂质代谢。rhyQTL的鉴定揭示了基因节律性的遗传机制，为人类疾病风险的变异提供了机制性见解，并为患者实现精准的时间治疗方法。
