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

Area of Science:

• Genetics
• Chronobiology
• Systems Biology

Background:

• 24-hour biological rhythms are crucial for physiological homeostasis.
• Disruptions in these rhythms elevate disease risks.
• The genetic basis of biological rhythms is known, but individual genetic variation's role in the oscillating transcriptome and its contribution to human chronophysiology and disease risk remain largely unexplored.

Purpose of the Study:

• To map interactions between temporal gene expression and genotype.
• To identify quantitative trait loci (QTLs) that influence rhythmic gene expression.
• To understand how genetic variation shapes rhythmic gene expression in human subpopulations.

Main Methods:

• Mapping interactions between temporal gene expression and genotype.
• Identification and nomenclature of rhythmic QTLs (rhyQTLs).
• Analysis of rhyQTLs' functional roles in chronophysiological processes.

Main Results:

• Identified novel rhythmic QTLs (rhyQTLs) that regulate previously unappreciated rhythmic genes.
• Demonstrated that rhyQTLs influence gene expression in specific human subpopulations based on genotype.
• Found that rhyQTLs and their associated rhythmic genes are extensively involved in essential chronophysiological processes, including bile acid and lipid metabolism.

Conclusions:

• Rhythmic QTLs provide insight into the genetic mechanisms underlying gene rhythmicity.
• The findings offer mechanistic explanations for variations in human disease risk related to biological rhythms.
• This research enables the development of precision chronotherapeutic strategies for patients.