Genetic determinants of lipids and cardiovascular disease outcomes: a wide-angled Mendelian randomization investigation
Genetic determinants of lipids and cardiovascular disease outcomes: a wide-angled Mendelian randomization investigation
ABSTRACT AimsTo systematically investigate causal relationships between circulating lipids and cardiovascular outcomes, using a Mendelian randomization approach. Methods and ResultsIn the primary analysis, we performed two-sample multivariable Mendelian randomization using data from participants of European ancestry. We also conducted univariable analyses using inverse-variance weighted and robust methods, and gene-specific analyses using variants that can be considered as proxies for specific lipid-lowering medications. We obtained associations with lipid fractions from the Global Lipids Genetics Consortium, a meta-analysis of 188,577 participants, and genetic associations with cardiovascular outcomes from 367,703 participants in UK Biobank.For LDL-cholesterol, in addition to the expected positive associations with coronary artery disease (CAD) risk (odds ratio per 1 standard deviation increase [OR], 1.45; 95% confidence interval [95%CI] 1.35-1.57) and other atheromatous outcomes (ischemic cerebrovascular disease and peripheral vascular disease), we found independent associations of genetically-predicted LDL-cholesterol with abdominal aortic aneurysm (OR 1.75; 95%CI 1.40-2.17), and aortic valve stenosis (OR 1.46; 95%CI 1.25-1.70). Genetically-predicted triglyceride levels were positively associated with CAD (OR 1.25; 95%CI 1.12-1.40), aortic valve stenosis (OR 1.29; 95%CI 1.04-1.61), and hypertension (OR 1.17; 95%CI 1.07-1.27), but inversely associated with venous thromboembolism (OR 0.79; 95%CI 0.67-0.93). The positive associations of genetically-predicted LDL-cholesterol and triglycerides with heart failure and aortic stenosis appeared to be mediated by CAD. ConclusionLowering LDL-cholesterol is likely to prevent abdominal aortic aneurysm and aortic stenosis, in addition to CAD and other atheromatous cardiovascular outcomes. Lowering triglycerides is likely to prevent CAD and aortic valve stenosis, but may increase risk of thromboembolism.
Allara Elias、Carter Paul、Gkatzionis Apostolos、Foley Christopher N、Butterworth Adam S、Angelantonio Emanuele Di、Morani Gabriele、Peters James、Mason Amy M、Rees Jessica MB、Bell Steven、Gill Dipender、Zuber Verena、Burgess Stephen
MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge||National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of CambridgeMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of CambridgeMRC Biostatistics Unit, University of CambridgeMRC Biostatistics Unit, University of CambridgeMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge||National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of CambridgeMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge||National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of CambridgeDipartimento di Scienze del Sistema Nervoso e del Comportamento, Universit¨¤ degli studi di PaviaMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of CambridgeMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of CambridgeMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge||Edinburgh Clinical Trials Unit, Usher Institute of Population Health Sciences and Informatics, University of EdinburghMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge||National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of CambridgeDepartment of Epidemiology and Biostatistics, Imperial College LondonMRC Biostatistics Unit, University of Cambridge||Department of Epidemiology and Biostatistics, Imperial College LondonMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge||MRC Biostatistics Unit, University of Cambridge
医学研究方法内科学遗传学
LipidsCardiovascular diseaseAetiologyEpidemiologyMendelian randomization
Allara Elias,Carter Paul,Gkatzionis Apostolos,Foley Christopher N,Butterworth Adam S,Angelantonio Emanuele Di,Morani Gabriele,Peters James,Mason Amy M,Rees Jessica MB,Bell Steven,Gill Dipender,Zuber Verena,Burgess Stephen.Genetic determinants of lipids and cardiovascular disease outcomes: a wide-angled Mendelian randomization investigation[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/668970.点此复制
评论