High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study
Background: To assess whether genetically determined quantitative and qualitative HDL characteristics were independently associated with coronary artery disease (CAD). Methods: We designed a two-sample multivariate Mendelian randomization study with available genome-wide association summary data. We...
| Autores: | , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p10204 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10204 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85090408499&doi=10.1016%2fj.metabol.2020.154351&partnerID=40&md5=73bf731feaae5797ce858007b1f1c373 |
| Access Level: | acceso abierto |
| Palabra clave: | apolipoprotein A1 cholesterol high density lipoprotein high density lipoprotein cholesterol low density lipoprotein cholesterol triacylglycerol Article cardiovascular risk cholesterol level coronary artery disease genetic correlation genetic variability high density lipoprotein cholesterol level human licence major clinical study Mendelian randomization analysis priority journal protein analysis qualitative analysis quantitative analysis triacylglycerol level blood genetic predisposition genetics genome-wide association study single nucleotide polymorphism Apolipoprotein A-I Cholesterol, HDL Coronary Artery Disease Genetic Predisposition to Disease Genome-Wide Association Study Humans Mendelian Randomization Analysis Polymorphism, Single Nucleotide |
| Sumario: | Background: To assess whether genetically determined quantitative and qualitative HDL characteristics were independently associated with coronary artery disease (CAD). Methods: We designed a two-sample multivariate Mendelian randomization study with available genome-wide association summary data. We identified genetic variants associated with HDL cholesterol and apolipoprotein A-I levels, HDL size, particle levels, and lipid content to define our genetic instrumental variables in one sample (Kettunen et al. study, n = 24,925) and analyzed their association with CAD risk in a different study (CARDIoGRAMplusC4D, n = 184,305). We validated these results by defining our genetic variables in another database (METSIM, n = 8372) and studied their relationship with CAD in the CARDIoGRAMplusC4D dataset. To estimate the effect size of the associations of interest adjusted for other lipoprotein traits and minimize potential pleiotropy, we used the Multi-trait-based Conditional & Joint analysis. Results: Genetically determined HDL cholesterol and apolipoprotein A-I levels were not associated with CAD. HDL mean diameter (ß = 0.27 [95%CI = 0.19; 0.35]), cholesterol levels in very large HDLs (ß = 0.29 [95%CI = 0.17; 0.40]), and triglyceride content in very large HDLs (ß = 0.14 [95%CI = 0.040; 0.25]) were directly associated with CAD risk, whereas the cholesterol content in medium-sized HDLs (ß = -0.076 [95%CI = -0.10; -0.052]) was inversely related to this risk. These results were validated in the METSIM-CARDIoGRAMplusC4D data. Conclusions: Some qualitative HDL characteristics (related to size, particle distribution, and cholesterol and triglyceride content) are related to CAD risk while HDL cholesterol levels are not. © 2020 The Authors |
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