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 i...

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Detalles Bibliográficos
Autores: Prats Uribe, Albert, Sayols Baixeras, Sergi, Fernández Sanlés, Alba, Subirana, Isaac, Carreras-Torres, Robert, Vilahur, Gemma, Civeira, Fernando, Marrugat, Jaume, Fitó Colomer, Montserrat, Hernáez, Álvaro, Elosua Llanos, Roberto
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:20.500.14342/3955
Acceso en línea:http://hdl.handle.net/20.500.14342/3955
https://doi.org/10.1016/j.metabol.2020.154351
Access Level:acceso abierto
Palabra clave:Lipoproteïnes de densitat alta
Sistema cardiovascular -- Malalties
Variables aleatòries
Aleatorització Mendeliana
Malalties coronàries
616.1
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spelling High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization studyPrats Uribe, AlbertSayols Baixeras, SergiFernández Sanlés, AlbaSubirana, IsaacCarreras-Torres, RobertVilahur, GemmaCiveira, FernandoMarrugat, JaumeFitó Colomer, MontserratHernáez, ÁlvaroElosua Llanos, RobertoLipoproteïnes de densitat altaSistema cardiovascular -- MalaltiesVariables aleatòriesAleatorització MendelianaMalalties coronàries616.1Background 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 (β = 0.27 [95%CI = 0.19; 0.35]), cholesterol levels in very large HDLs (β = 0.29 [95%CI = 0.17; 0.40]), and triglyceride content in very large HDLs (β = 0.14 [95%CI = 0.040; 0.25]) were directly associated with CAD risk, whereas the cholesterol content in medium-sized HDLs (β = −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.info:eu-repo/semantics/acceptedVersionElsevierUniversitat Ramon Llull. Facultat de Ciències de la Salut Blanquerna2020info:eu-repo/semantics/article7 p.http://hdl.handle.net/20.500.14342/3955https://doi.org/10.1016/j.metabol.2020.154351reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésMetabolism Clinical and Experimental, 2020, 112: 154351info:eu-repo/grantAgreement/MINECO/ISCIII i FEDER/CD17info:eu-repo/grantAgreement/MINECO/ISCIII i FEDER/IFI14info:eu-repo/grantAgreement/MINECO/ISCIII i FEDER/PI18info:eu-repo/grantAgreement/MRC/MR/K501256info:eu-repo/grantAgreement/MRC/MR/N013468info:eu-repo/grantAgreement/MINECO/PN I+D/BES-2014-069718info:eu-repo/grantAgreement/MINECO/PN I+D/SAF2015-71653-Rinfo:eu-repo/grantAgreement/EU/H2020/796216info:eu-repo/grantAgreement/SUR del DEC/SGR/2017 SGR 222© Elsevier. Tots els drets reservatsinfo:eu-repo/semantics/openAccessoai:recercat.cat:20.500.14342/39552026-05-29T05:05:01Z
dc.title.none.fl_str_mv High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study
title High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study
spellingShingle High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study
Prats Uribe, Albert
Lipoproteïnes de densitat alta
Sistema cardiovascular -- Malalties
Variables aleatòries
Aleatorització Mendeliana
Malalties coronàries
616.1
title_short High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study
title_full High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study
title_fullStr High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study
title_full_unstemmed High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study
title_sort High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study
dc.creator.none.fl_str_mv Prats Uribe, Albert
Sayols Baixeras, Sergi
Fernández Sanlés, Alba
Subirana, Isaac
Carreras-Torres, Robert
Vilahur, Gemma
Civeira, Fernando
Marrugat, Jaume
Fitó Colomer, Montserrat
Hernáez, Álvaro
Elosua Llanos, Roberto
author Prats Uribe, Albert
author_facet Prats Uribe, Albert
Sayols Baixeras, Sergi
Fernández Sanlés, Alba
Subirana, Isaac
Carreras-Torres, Robert
Vilahur, Gemma
Civeira, Fernando
Marrugat, Jaume
Fitó Colomer, Montserrat
Hernáez, Álvaro
Elosua Llanos, Roberto
author_role author
author2 Sayols Baixeras, Sergi
Fernández Sanlés, Alba
Subirana, Isaac
Carreras-Torres, Robert
Vilahur, Gemma
Civeira, Fernando
Marrugat, Jaume
Fitó Colomer, Montserrat
Hernáez, Álvaro
Elosua Llanos, Roberto
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Ramon Llull. Facultat de Ciències de la Salut Blanquerna
dc.subject.none.fl_str_mv Lipoproteïnes de densitat alta
Sistema cardiovascular -- Malalties
Variables aleatòries
Aleatorització Mendeliana
Malalties coronàries
616.1
topic Lipoproteïnes de densitat alta
Sistema cardiovascular -- Malalties
Variables aleatòries
Aleatorització Mendeliana
Malalties coronàries
616.1
description 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 (β = 0.27 [95%CI = 0.19; 0.35]), cholesterol levels in very large HDLs (β = 0.29 [95%CI = 0.17; 0.40]), and triglyceride content in very large HDLs (β = 0.14 [95%CI = 0.040; 0.25]) were directly associated with CAD risk, whereas the cholesterol content in medium-sized HDLs (β = −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.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.14342/3955
https://doi.org/10.1016/j.metabol.2020.154351
url http://hdl.handle.net/20.500.14342/3955
https://doi.org/10.1016/j.metabol.2020.154351
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Metabolism Clinical and Experimental, 2020, 112: 154351
info:eu-repo/grantAgreement/MINECO/ISCIII i FEDER/CD17
info:eu-repo/grantAgreement/MINECO/ISCIII i FEDER/IFI14
info:eu-repo/grantAgreement/MINECO/ISCIII i FEDER/PI18
info:eu-repo/grantAgreement/MRC/MR/K501256
info:eu-repo/grantAgreement/MRC/MR/N013468
info:eu-repo/grantAgreement/MINECO/PN I+D/BES-2014-069718
info:eu-repo/grantAgreement/MINECO/PN I+D/SAF2015-71653-R
info:eu-repo/grantAgreement/EU/H2020/796216
info:eu-repo/grantAgreement/SUR del DEC/SGR/2017 SGR 222
dc.rights.none.fl_str_mv © Elsevier. Tots els drets reservats
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © Elsevier. Tots els drets reservats
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 7 p.
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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