Research squareJan 9, 2026

Genetic links to daily rhythm imbalance related to diabetes, mood, and heart attack in over 300,000 Europeans

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

A polygenic Circadian Imbalance Index was linked to metabolic, cardiovascular, and mood-related traits in UK Biobank participants of European ancestry.

Evidence

This was a GWAS of CII in 312,935 European ancestry UK Biobank participants, with gene-overlap, polygenic score, genetic correlation, phenome-wide, and Mendelian randomization analyses.

Caveat

The findings depend on a composite index and largely European ancestry biobank data, and Mendelian randomization signals do not establish all mechanisms or clinical utility.

Simplified

The Circadian Imbalance Index (CII) integrates chronotype, sleep duration, neuroticism, caffeine intake, and vitamin D. In a genome wide association study (GWAS) of CII in 312,935 European ancestry UK Biobank participants, we identified 27 loci mapping to 72 genes, including circadian regulators CALCA, DHCR7, KDM5A, HAL, and CRX. Gene-overlap analyses demonstrated shared architecture with CII components, while EPHB1, SERPING1, C12orf74, PLEKHG7, and EEA1 were uniquely associated with CII. A CII polygenic score (CII-PRS) showed phenome-wide associations with type 2 diabetes (T2D), major depressive disorder, and obesity. Genetic correlations linked CII with insomnia, mood symptoms, body mass index (BMI), T2D, coronary artery disease (CAD), and myocardial infarction (MI). Mendelian randomization suggested causal effects of CII on T2D, mood swings, and MI, and reverse effects of CAD, mood, and MI on CII. This work shows that circadian imbalance is a polygenic trait connecting sleep-related biology to metabolic, cardiovascular and mood health outcomes.