A genome-wide association study of imaging-defined atherosclerosisDepartment of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden.
School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden.
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg, Sweden.
Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden; Department of Clinical Physiology in Linköping, Linköping University, Linköping, Sweden; Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
Department of Clinical Sciences Lund, Cardiology, Lund University, Lund, Sweden.
Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Sciences, Clinical Epidemiology, Uppsala University, Uppsala, Sweden.
Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden; Department of Emergency and Internal Medicine, Skåne University Hospital, Malmö, Sweden.
Region Västra Götaland, Sahlgrenska University Hospital, Department of Cardiology, Gothenburg, Sweden.
Department of Medical Sciences, Uppsala University, Uppsala, Sweden; The George Institute for Global Health, University of New South Wales, Sydney, Australia.
Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden; Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
Department of Biomedical and Clinical Sciences, Division of Clinical Genetics, Linköping University, Linköping, Sweden.
Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden.
Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
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2025 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 16, no 1, article id 2266Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
Nature Publishing Group, 2025. Vol. 16, no 1, article id 2266
National Category
Cardiology and Cardiovascular Disease Medical Genetics and Genomics
Identifiers
URN: urn:nbn:se:umu:diva-237375DOI: 10.1038/s41467-025-57457-7ISI: 001456731600020PubMedID: 40164586Scopus ID: 2-s2.0-105001450683OAI: oai:DiVA.org:umu-237375DiVA, id: diva2:1953978
Funder
Swedish Heart Lung Foundation, 2023-0439Swedish Heart Lung Foundation, 2024-1135Swedish Heart Lung Foundation, 2024-1137Swedish Research Council, 2023-021772025-04-232025-04-232025-04-23Bibliographically approved