Evidence map›Paper›PMID 40999520›Full record

ArticleGenome biology2025

Dissecting the genetic architecture of circadian rhythms in human tissues using a quantitative circadian deviation score.

Zheyu Li, Liang Chen

Abstract read
In one paragraph

Article in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

2 authors.

Zheyu LiMork Family Department of Chemical Engineering and Materials Science, University of Southern California, 925 Bloom Walk, Los Angeles, CA, 90089, USA.
Liang ChenDepartment of Quantitative and Computational Biology, University of Southern California, 1050 Childs Way, Los Angeles, CA, 90089, USA. liang.chen@usc.edu.

Funding

Genetic control mechanisms of long-term neuronal survivalR01NS139485 · NINDS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Sika Zheng · 2024 to 2026
$1.9M
NINDS NIH HHS R01 NS139485USA NIH R01NS139485
6 · The paper itself

Abstract

backgroundCircadian rhythms influence various physiological and behavioral processes, including sleep, metabolism, and immune response. Although key regulatory factors of biological clocks have been identified and genome-wide association studies have pinpointed some genetic variants linked to sleep traits, the genetic architecture underlying circadian rhythms remains incompletely understood.

resultsHere, we introduce the circadian deviation score, a novel quantitative trait that measures circadian disruption at the molecular level. Derived from gene expression levels of thousands of circadian genes across Human tissues, this score helps identify tissue-specific genetic influences on circadian rhythms. Our analysis reveals 654 SNPs, which we named Circ-SNPs, associated with global circadian disruption at the expression level. These include previously known SNPs Linked to insomnia, chronotype, and circadian rhythm, as well as new SNPs that enhance understanding of circadian regulation. Most Circ-SNPs exhibit significant associations with the circadian deviation score in the small intestine and adrenal gland, with about 19.4% situated on the X chromosome, highlighting sex-specific differences in circadian disorders. Circ-SNPs often reside near the 3' end of transcripts, indicating their potential regulatory roles, particularly in post-transcriptional processes. The genes harboring Circ-SNPs, which we named Circ-regulators, are enriched for known circadian traits. DrugBank analysis shows 18 of 122 protein-coding Circ-regulators are targetable by 163 existing drugs, including six approved for sleep disorders.

conclusionsOur findings highlight the potential for repurposing existing drugs to treat circadian-related disorders and provide a deeper understanding of the genetic components of circadian rhythms and sleep disorders.

Indexed as

Circadian RhythmFemaleGenome-Wide Association StudyHumansMaleOrgan SpecificityPolymorphism, Single NucleotideQuantitative Trait Loci

Identifiers

PMID40999520
PMCPMC12462297

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.