Evidence map›Paper›PMID 41510233›Full record

ArticleResearch square2025

Genome wide association study of a Circadian Imbalance Index in 312,935 European ancestry UK Biobank participants identifies loci related to diabetes, mood and myocardial infarction.

Magdalena Żebrowska, Matthias Wielscher, Jing Zhang, Ingvild Saksvik-Lehouillier, Lee DiMilia, Angus Burns, Jesse Valliere, Leonardo Vincenzi, Susan Redline, Olivia I Okereke and 4 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Magdalena ŻebrowskaMedical University of Vienna.ORCID 0000-0003-0589-4173
Matthias WielscherMedical University of Vienna.ORCID 0000-0003-4138-1383
Jing ZhangNanjing Medical University.
Ingvild Saksvik-LehouillierNorwegian University of Science and Technology.
Lee DiMiliaCentral Queensland University.
Angus BurnsBrigham and Women's Hospital, Harvard Medical School.ORCID 0000-0001-6336-5531
Jesse ValliereCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114.
Leonardo VincenziMedical University of Vienna.
Susan RedlineBrigham and Women's Hospital.ORCID 0000-0002-6585-1610
Olivia I OkerekeDepartment of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02215, USA.
Richa SaxenaMassachusetts General Hospital.
Rebecca RichmondUniversity of Bristol.ORCID 0000-0003-0574-5071
Martin RutterUniversity of Manchester.
Eva SchernhammerDepartment of Epidemiology, Center for Public Health, Medical University of Vienna, Vienna, Austria.

Funding

Life Course Cancer Epidemiology Cohort in WomenU01CA176726 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI ELIASSEN, A. HEATHER, WILLETT, WALTER C. · 2018 to 2025
$22.4M
Integrating lifecourse approaches, biologic and digital phenotypes in support of heart and lung disease epidemiologic researchU01HL145386 · NHLBI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI CHAVARRO, JORGE EDUARDO, MANSON, JOANN ELISABETH · 2019 to 2025
$17.8M
Premonopausal Hormone Levels and Risk of Breast CancerR01CA067262 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI HANKINSON, SUSAN E · 2002 to 2011
$11.9M
NCI NIH HHS R01 CA067262NCI NIH HHS U01 CA176726NHLBI NIH HHS U01 HL145386
6 · The paper itself

Abstract

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.

Indexed as

circadian disruptionCircadian Imbalance Indexeffect modificationGWASshift work

Identifiers

PMID41510233
PMCPMC12776499

What Socratic holds

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Registered trials

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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 Socratic graph.