IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59524-5.html
   My bibliography  Save this article

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

Author

Listed:
  • Ying Chen

    (Baylor College of Medicine)

  • Panpan Liu

    (Baylor College of Medicine)

  • Aniko Sabo

    (Baylor College of Medicine)

  • Dongyin Guan

    (Baylor College of Medicine)

Abstract

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

Suggested Citation

  • Ying Chen & Panpan Liu & Aniko Sabo & Dongyin Guan, 2025. "Human genetic variation determines 24-hour rhythmic gene expression and disease risk," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59524-5
    DOI: 10.1038/s41467-025-59524-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59524-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-59524-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Chen-Jie Fei & Ze-Yu Li & Jing Ning & Liu Yang & Bang-Sheng Wu & Ju-Jiao Kang & Wei-Shi Liu & Xiao-Yu He & Jia You & Shi-Dong Chen & Huan Yu & Zhi-Li Huang & Jian-Feng Feng & Jin-Tai Yu & Wei Cheng, 2024. "Exome sequencing identifies genes associated with sleep-related traits," Nature Human Behaviour, Nature, vol. 8(3), pages 576-589, March.
    2. Samuel E. Jones & Jacqueline M. Lane & Andrew R. Wood & Vincent T. Hees & Jessica Tyrrell & Robin N. Beaumont & Aaron R. Jeffries & Hassan S. Dashti & Melvyn Hillsdon & Katherine S. Ruth & Marcus A. T, 2019. "Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    3. Claudia Giambartolomei & Damjan Vukcevic & Eric E Schadt & Lude Franke & Aroon D Hingorani & Chris Wallace & Vincent Plagnol, 2014. "Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics," PLOS Genetics, Public Library of Science, vol. 10(5), pages 1-15, May.
    4. Kyle Kai-How Farh & Alexander Marson & Jiang Zhu & Markus Kleinewietfeld & William J. Housley & Samantha Beik & Noam Shoresh & Holly Whitton & Russell J. H. Ryan & Alexander A. Shishkin & Meital Hatan, 2015. "Genetic and epigenetic fine mapping of causal autoimmune disease variants," Nature, Nature, vol. 518(7539), pages 337-343, February.
    5. Tanya M. Teslovich & Kiran Musunuru & Albert V. Smith & Andrew C. Edmondson & Ioannis M. Stylianou & Masahiro Koseki & James P. Pirruccello & Samuli Ripatti & Daniel I. Chasman & Cristen J. Willer & C, 2010. "Biological, clinical and population relevance of 95 loci for blood lipids," Nature, Nature, vol. 466(7307), pages 707-713, August.
    6. Leonidas S. Lundell & Evelyn B. Parr & Brooke L. Devlin & Lars R. Ingerslev & Ali Altıntaş & Shogo Sato & Paolo Sassone-Corsi & Romain Barrès & Juleen R. Zierath & John A. Hawley, 2020. "Time-restricted feeding alters lipid and amino acid metabolite rhythmicity without perturbing clock gene expression," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    7. Marianne L. Seney & Kelly Cahill & John F. Enwright & Ryan W. Logan & Zhiguang Huo & Wei Zong & George Tseng & Colleen A. McClung, 2019. "Diurnal rhythms in gene expression in the prefrontal cortex in schizophrenia," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    8. Chris Wallace, 2021. "A more accurate method for colocalisation analysis allowing for multiple causal variants," PLOS Genetics, Public Library of Science, vol. 17(9), pages 1-11, September.
    9. Gao Wang & Abhishek Sarkar & Peter Carbonetto & Matthew Stephens, 2020. "A simple new approach to variable selection in regression, with application to genetic fine mapping," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 82(5), pages 1273-1300, December.
    10. Yuxin Zou & Peter Carbonetto & Gao Wang & Matthew Stephens, 2022. "Fine-mapping from summary data with the “Sum of Single Effects” model," PLOS Genetics, Public Library of Science, vol. 18(7), pages 1-24, July.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Ichcha Manipur & Guillermo Reales & Jae Hoon Sul & Myung Kyun Shin & Simonne Longerich & Adrian Cortes & Chris Wallace, 2024. "CoPheScan: phenome-wide association studies accounting for linkage disequilibrium," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Yihe Yang & Noah Lorincz-Comi & Xiaofeng Zhu, 2025. "Uncovering causal gene-tissue pairs and variants through a multivariate TWAS controlling for infinitesimal effects," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    3. Sourya Bhattacharyya & Ferhat Ay, 2024. "Identifying genetic variants associated with chromatin looping and genome function," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    4. Bryan R. Gorman & Sun-Gou Ji & Michael Francis & Anoop K. Sendamarai & Yunling Shi & Poornima Devineni & Uma Saxena & Elizabeth Partan & Andrea K. DeVito & Jinyoung Byun & Younghun Han & Xiangjun Xiao, 2024. "Multi-ancestry GWAS meta-analyses of lung cancer reveal susceptibility loci and elucidate smoking-independent genetic risk," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Sylvia Hartmann & Summaira Yasmeen & Benjamin M. Jacobs & Spiros Denaxas & Munir Pirmohamed & Eric R. Gamazon & Mark J. Caulfield & Harry Hemingway & Maik Pietzner & Claudia Langenberg, 2023. "ADRA2A and IRX1 are putative risk genes for Raynaud’s phenomenon," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    7. Emma Hazelwood & Daffodil M. Canson & Benedita Deslandes & Xuemin Wang & Pik Fang Kho & Danny Legge & Andrei-Emil Constantinescu & Matthew A. Lee & D. Timothy Bishop & Andrew T. Chan & Stephen B. Grub, 2025. "Multi-tissue expression and splicing data prioritise anatomical subsite- and sex-specific colorectal cancer susceptibility genes," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    8. Wesley L Crouse & Gregory R Keele & Madeleine S Gastonguay & Gary A Churchill & William Valdar, 2022. "A Bayesian model selection approach to mediation analysis," PLOS Genetics, Public Library of Science, vol. 18(5), pages 1-33, May.
    9. Valur Emilsson & Elias F. Gudmundsson & Thorarinn Jonmundsson & Brynjolfur G. Jonsson & Michael Twarog & Valborg Gudmundsdottir & Zhiguang Li & Nancy Finkel & Stephen Poor & Xin Liu & Robert Esterberg, 2022. "A proteogenomic signature of age-related macular degeneration in blood," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    10. Wenhan Chen & Yang Wu & Zhili Zheng & Ting Qi & Peter M. Visscher & Zhihong Zhu & Jian Yang, 2021. "Improved analyses of GWAS summary statistics by reducing data heterogeneity and errors," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    11. Adriaan Graaf & Robert Warmerdam & Chiara Auwerx & Urmo Võsa & Maria Carolina Borges & Lude Franke & Zoltán Kutalik, 2025. "MR-link-2: pleiotropy robust cis Mendelian randomization validated in three independent reference datasets of causality," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    12. Bayram Cevdet Akdeniz & Oleksandr Frei & Alexey Shadrin & Dmitry Vetrov & Dmitry Kropotov & Eivind Hovig & Ole A Andreassen & Anders M Dale, 2024. "Finemap-MiXeR: A variational Bayesian approach for genetic finemapping," PLOS Genetics, Public Library of Science, vol. 20(8), pages 1-21, August.
    13. V. E. Jackson & Y. Wu & R. Bonelli & J. P. Owen & L. W. Scott & S. Farashi & Y. Kihara & M. L. Gantner & C. Egan & K. M. Williams & B. R. E. Ansell & A. Tufail & A. Y. Lee & M. Bahlo, 2025. "Multi-omic spatial effects on high-resolution AI-derived retinal thickness," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    14. Mary P. LaPierre & Katherine Lawler & Svenja Godbersen & I. Sadaf Farooqi & Markus Stoffel, 2022. "MicroRNA-7 regulates melanocortin circuits involved in mammalian energy homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    15. Yon Ho Jee & Ying Wang & Keum Ji Jung & Ji-Young Lee & Heejin Kimm & Rui Duan & Alkes L. Price & Alicia R. Martin & Peter Kraft, 2025. "Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    16. Matthew T. Patrick & Qinmengge Li & Rachael Wasikowski & Nehal Mehta & Johann E. Gudjonsson & James T. Elder & Xiang Zhou & Lam C. Tsoi, 2022. "Shared genetic risk factors and causal association between psoriasis and coronary artery disease," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    17. Hanmin Guo & Alexander Eckehart Urban & Wing Hung Wong, 2024. "Prioritizing disease-related rare variants by integrating gene expression data," PLOS Genetics, Public Library of Science, vol. 20(9), pages 1-16, September.
    18. Linda Ottensmann & Rubina Tabassum & Sanni E. Ruotsalainen & Mathias J. Gerl & Christian Klose & Elisabeth Widén & Kai Simons & Samuli Ripatti & Matti Pirinen, 2023. "Genome-wide association analysis of plasma lipidome identifies 495 genetic associations," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    19. Amil M. Shah & Peder L. Myhre & Victoria Arthur & Pranav Dorbala & Humaira Rasheed & Leo F. Buckley & Brian Claggett & Guning Liu & Jianzhong Ma & Ngoc Quynh Nguyen & Kunihiro Matsushita & Chiadi Ndum, 2024. "Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    20. Priya Gupta & Marco Galimberti & Yue Liu & Sarah Beck & Aliza Wingo & Thomas Wingo & Keyrun Adhikari & Henry R. Kranzler & Murray B. Stein & Joel Gelernter & Daniel F. Levey, 2024. "A genome-wide investigation into the underlying genetic architecture of personality traits and overlap with psychopathology," Nature Human Behaviour, Nature, vol. 8(11), pages 2235-2249, November.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59524-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.