dc.contributor |
Landspitali - The National University Hospital of Iceland |
dc.contributor.author |
DBDS Genomic Consortium |
dc.date.accessioned |
2023-01-13T01:04:36Z |
dc.date.available |
2023-01-13T01:04:36Z |
dc.date.issued |
2022-12-21 |
dc.identifier.citation |
DBDS Genomic Consortium 2022 , ' Cholesterol not particle concentration mediates the atherogenic risk conferred by apolipoprotein B particles : a Mendelian randomization analysis ' , European Journal of Preventive Cardiology , vol. 29 , no. 18 , pp. 2374-2385 . https://doi.org/10.1093/eurjpc/zwac219 |
dc.identifier.issn |
2047-4873 |
dc.identifier.other |
72039251 |
dc.identifier.other |
f8a7928e-abb3-415c-9716-f9e537b10c12 |
dc.identifier.other |
36125206 |
dc.identifier.other |
85154045599 |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/3848 |
dc.description |
© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. |
dc.description.abstract |
BACKGROUND AND AIMS: The causal contribution of apolipoprotein B (apoB) particles to coronary artery disease (CAD) is established. We examined whether this atherogenic contribution is better reflected by non-high-density lipoprotein cholesterol (non-HDL-C) or apoB particle concentration. METHOD AND RESULTS: We performed Mendelian randomization (MR) analysis using 235 variants as genetic instruments; testing the relationship between their effects on the exposures, non-HDL-C and apoB, and on the outcome CAD using weighted regression. Variant effect estimates on the exposures came from the UK Biobank (N = 376 336) and on the outcome from a meta-analysis of five CAD datasets (187 451 cases and 793 315 controls). Subsequently, we carried out sensitivity and replication analyses.In univariate MR analysis, both exposures associated with CAD (βnon-HDL-C = 0.40, P = 2.8 × 10-48 and βapoB = 0.38, P = 1.3 × 10-44). Adding effects on non-HDL-C into a model that already included those on apoB significantly improved the genetically predicted CAD effects (P = 3.9 × 10-5), while adding apoB into the model including non-HDL-C did not (P = 0.69). Thirty-five per cent (82/235) of the variants used as genetic instruments had discordant effects on the exposures, associating with non-HDL-C/apoB ratio at P < 2.1 × 10-4 (0.05/235). Fifty-one variants associated at genome-wide significance. CONCLUSION: Many sequence variants have discordant effects on non-HDL-C and apoB. These variants allowed us to show that the causal mechanism underlying the relationship between apolipoprotein B particles and CAD is more associated with non-HDL-C than apoB particle concentration. |
dc.format.extent |
12 |
dc.format.extent |
781649 |
dc.format.extent |
2374-2385 |
dc.language.iso |
en |
dc.relation.ispartofseries |
European Journal of Preventive Cardiology; 29(18) |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Lífefna- og sameindalíffræði |
dc.subject |
Innkirtlalæknisfræði |
dc.subject |
Hjartalæknisfræði |
dc.subject |
Humans |
dc.subject |
Mendelian Randomization Analysis |
dc.subject |
Cholesterol, LDL |
dc.subject |
Risk Factors |
dc.subject |
Cholesterol |
dc.subject |
Apolipoproteins B/genetics |
dc.subject |
Coronary Artery Disease/genetics |
dc.subject |
Atherosclerosis |
dc.subject |
Lipoproteins |
dc.subject |
Cholesterol, HDL |
dc.subject |
Apolipoprotein B-100/genetics |
dc.title |
Cholesterol not particle concentration mediates the atherogenic risk conferred by apolipoprotein B particles : a Mendelian randomization analysis |
dc.type |
/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article |
dc.description.version |
Peer reviewed |
dc.identifier.doi |
10.1093/eurjpc/zwac219 |
dc.contributor.department |
Faculty of Physical Sciences |
dc.contributor.department |
Faculty of Medicine |
dc.contributor.school |
Health Sciences |