IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-57457-7.html
   My bibliography  Save this article

A genome-wide association study of imaging-defined atherosclerosis

Author

Listed:
  • Anders Gummesson

    (Department of Clinical Genetics and Genomics
    University of Gothenburg)

  • Per Lundmark

    (Uppsala University)

  • Qiao Sen Chen

    (Karolinska Institutet)

  • Elias Björnson

    (University of Gothenburg)

  • Koen F. Dekkers

    (Uppsala University)

  • Ulf Hammar

    (Uppsala University)

  • Martin Adiels

    (University of Gothenburg)

  • Yunzhang Wang

    (Karolinska Institutet)

  • Therese Andersson

    (Umeå University)

  • Göran Bergström

    (University of Gothenburg
    Department of Clinical Physiology)

  • Carl-Johan Carlhäll

    (Linköping University
    Linköping University
    Linköping University)

  • David Erlinge

    (Lund University)

  • Tomas Jernberg

    (Karolinska Institutet)

  • Fredrik Landfors

    (Umeå University)

  • Lars Lind

    (Uppsala University)

  • Maria Mannila

    (Karolinska University Hospital)

  • Olle Melander

    (Lund University
    Skåne University Hospital)

  • Carlo Pirazzi

    (Department of Cardiology)

  • Johan Sundström

    (Uppsala University
    University of New South Wales)

  • Carl Johan Östgren

    (Linköping University
    Linköping University)

  • Cecilia Gunnarsson

    (Linköping University)

  • Marju Orho-Melander

    (Lund University)

  • Stefan Söderberg

    (Umeå University)

  • Tove Fall

    (Uppsala University)

  • Bruna Gigante

    (Karolinska Institutet
    Karolinska University Hospital)

Abstract

Imaging-defined atherosclerosis represents an intermediate phenotype of atherosclerotic cardiovascular disease (ASCVD). Genome-wide association studies (GWAS) on directly measured coronary plaques using coronary computed tomography angiography (CCTA) are scarce. In the so far largest population-based cohort with CCTA data, we performed a GWAS on coronary plaque burden as determined by the segment involvement score (SIS) in 24,811 European individuals. We identified 20 significant independent genetic markers for SIS, three of which were found in loci not implicated in ASCVD before. Further GWAS on coronary artery calcification showed similar results to that of SIS, whereas a GWAS on ultrasound-assessed carotid plaques identified both shared and non-shared loci with SIS. In two-sample Mendelian randomization studies using SIS-associated markers in UK Biobank and CARDIoGRAMplusC4D, one extra coronary segment with atherosclerosis corresponded to 1.8-fold increased odds of myocardial infarction. This GWAS data can aid future studies of causal pathways in ASCVD.

Suggested Citation

  • Anders Gummesson & Per Lundmark & Qiao Sen Chen & Elias Björnson & Koen F. Dekkers & Ulf Hammar & Martin Adiels & Yunzhang Wang & Therese Andersson & Göran Bergström & Carl-Johan Carlhäll & David Erli, 2025. "A genome-wide association study of imaging-defined atherosclerosis," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57457-7
    DOI: 10.1038/s41467-025-57457-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-57457-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-57457-7?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. 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.
    2. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    3. Nora Franceschini & Claudia Giambartolomei & Paul S. Vries & Chris Finan & Joshua C. Bis & Rachael P. Huntley & Ruth C. Lovering & Salman M. Tajuddin & Thomas W. Winkler & Misa Graff & Maryam Kavousi , 2018. "GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    4. 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.
    5. Sarah E. Graham & Shoa L. Clarke & Kuan-Han H. Wu & Stavroula Kanoni & Greg J. M. Zajac & Shweta Ramdas & Ida Surakka & Ioanna Ntalla & Sailaja Vedantam & Thomas W. Winkler & Adam E. Locke & Eirini Ma, 2021. "The power of genetic diversity in genome-wide association studies of lipids," Nature, Nature, vol. 600(7890), pages 675-679, December.
    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. 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.
    2. 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.
    3. Tzu-Ting Chen & Jaeyoung Kim & Max Lam & Yi-Fang Chuang & Yen-Ling Chiu & Shu-Chin Lin & Sang-Hyuk Jung & Beomsu Kim & Soyeon Kim & Chamlee Cho & Injeong Shim & Sanghyeon Park & Yeeun Ahn & Aysu Okbay, 2024. "Shared genetic architectures of educational attainment in East Asian and European populations," Nature Human Behaviour, Nature, vol. 8(3), pages 562-575, March.
    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. 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.
    6. Isabelle Austin-Zimmerman & Daniel F. Levey & Olga Giannakopoulou & Joseph D. Deak & Marco Galimberti & Keyrun Adhikari & Hang Zhou & Spiros Denaxas & Haritz Irizar & Karoline Kuchenbaecker & Andrew M, 2023. "Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Xiaofeng Zhu & Yihe Yang & Noah Lorincz-Comi & Gen Li & Amy R. Bentley & Paul S. de Vries & Michael Brown & Alanna C. Morrison & Charles N. Rotimi & W. James Gauderman & Dabeeru C. Rao & Hugues Aschar, 2024. "An approach to identify gene-environment interactions and reveal new biological insight in complex traits," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    8. Sophie A. Riesmeijer & Zoha Kamali & Michael Ng & Dmitriy Drichel & Bram Piersma & Kerstin Becker & Thomas B. Layton & Jagdeep Nanchahal & Michael Nothnagel & Ahmad Vaez & Hans Christian Hennies & Pau, 2024. "A genome-wide association meta-analysis implicates Hedgehog and Notch signaling in Dupuytren’s disease," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    9. Danielle Rasooly & Gina M. Peloso & Alexandre C. Pereira & Hesam Dashti & Claudia Giambartolomei & Eleanor Wheeler & Nay Aung & Brian R. Ferolito & Maik Pietzner & Eric H. Farber-Eger & Quinn Stanton , 2023. "Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    10. Mingxuan Cai & Zhiwei Wang & Jiashun Xiao & Xianghong Hu & Gang Chen & Can Yang, 2023. "XMAP: Cross-population fine-mapping by leveraging genetic diversity and accounting for confounding bias," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. 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.
    12. Ananyo Choudhury & Jean-Tristan Brandenburg & Tinashe Chikowore & Dhriti Sengupta & Palwende Romuald Boua & Nigel J. Crowther & Godfred Agongo & Gershim Asiki & F. Xavier Gómez-Olivé & Isaac Kisiangan, 2022. "Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    13. 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.
    14. Eeva Sliz & Jaakko S. Tyrmi & Nilufer Rahmioglu & Krina T. Zondervan & Christian M. Becker & Outi Uimari & Johannes Kettunen, 2023. "Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    15. 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.
    16. 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.
    17. 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.
    18. Rosalie B. T. M. Sterenborg & Inga Steinbrenner & Yong Li & Melissa N. Bujnis & Tatsuhiko Naito & Eirini Marouli & Tessel E. Galesloot & Oladapo Babajide & Laura Andreasen & Arne Astrup & Bjørn Olav Å, 2024. "Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    19. Ruo-Han Hao & Tian-Pei Zhang & Feng Jiang & Jun-Hui Liu & Shan-Shan Dong & Meng Li & Yan Guo & Tie-Lin Yang, 2024. "Revealing brain cell-stratified causality through dissecting causal variants according to their cell-type-specific effects on gene expression," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    20. Shahram Bahrami & Kaja Nordengen & Jaroslav Rokicki & Alexey A. Shadrin & Zillur Rahman & Olav B. Smeland & Piotr P. Jaholkowski & Nadine Parker & Pravesh Parekh & Kevin S. O’Connell & Torbjørn Elvsås, 2024. "The genetic landscape of basal ganglia and implications for common brain disorders," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    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_s41467-025-57457-7. 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.