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

## TL;DR

This study shows how human genetic variation influences daily gene expression rhythms and disease risk.

## Contribution

The paper introduces rhythmic QTLs (rhyQTLs), which link genetic variation to rhythmic gene expression and disease risk.

## Key findings

- rhyQTLs determine rhythmic genes in human subpopulations with specific genotypes.
- rhyQTLs are involved in essential chronophysiological processes like bile acid and lipid metabolism.
- Identifying rhyQTLs provides insights into disease risk variation and potential precision chronotherapies.

## Abstract

24-hour biological rhythms are essential to maintain physiological homeostasis. Disruption of these rhythms increases the risks of multiple diseases. The 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.

Rhythmic quantitative trait loci explain individual variations in biological rhythms of gene expression and contribute to disease risk in humans.