Gummesson Anders, Lundmark Per, Chen Qiao Sen, Björnson Elias, Dekkers Koen F, Hammar Ulf, Adiels Martin, Wang Yunzhang, Andersson Therese, Bergström Göran, Carlhäll Carl-Johan, Erlinge David, Jernberg Tomas, Landfors Fredrik, Lind Lars, Mannila Maria, Melander Olle, Pirazzi Carlo, Sundström Johan, Östgren Carl Johan, Gunnarsson Cecilia, Orho-Melander Marju, Söderberg Stefan, Fall Tove, Gigante Bruna
Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Genetics and Genomics, Gothenburg, Sweden.
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Nat Commun. 2025 Mar 31;16(1):2266. doi: 10.1038/s41467-025-57457-7.
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.
影像学定义的动脉粥样硬化是动脉粥样硬化性心血管疾病（ASCVD）的一种中间表型。利用冠状动脉计算机断层扫描血管造影（CCTA）对直接测量的冠状动脉斑块进行全基因组关联研究（GWAS）的报道较少。在目前拥有CCTA数据的最大规模的基于人群的队列研究中，我们对24811名欧洲个体的冠状动脉斑块负荷进行了GWAS分析，该斑块负荷由节段累及评分（SIS）确定。我们确定了20个与SIS显著相关的独立基因标记，其中3个位于之前未发现与ASCVD相关的基因座。进一步对冠状动脉钙化进行的GWAS分析结果与SIS相似，而对超声评估的颈动脉斑块进行的GWAS分析则确定了与SIS共享和不共享的基因座。在两项使用英国生物银行和CARDIoGRAMplusC4D中与SIS相关标记的两样本孟德尔随机化研究中，多一个冠状动脉节段出现动脉粥样硬化，心肌梗死的几率增加1.8倍。这些GWAS数据有助于未来对ASCVD因果途径的研究。
