dc.contributor |
Háskóli Íslands |
dc.contributor |
University of Iceland |
dc.contributor.author |
Helgadottir, Anna |
dc.contributor.author |
Thorleifsson, Gudmar |
dc.contributor.author |
Alexandersson, Kristjan F |
dc.contributor.author |
Tragante, Vinicius |
dc.contributor.author |
Þorsteinsdóttir, Margrét |
dc.contributor.author |
Eiriksson, Finnur Freyr |
dc.contributor.author |
Grétarsdóttir, Sólveig |
dc.contributor.author |
Björnsson, Eyþór |
dc.contributor.author |
Magnússon, Ólafur |
dc.contributor.author |
Sveinbjornsson, Gardar |
dc.contributor.author |
Jonsdottir, Ingileif |
dc.contributor.author |
Steinthorsdottir, Valgerdur |
dc.contributor.author |
Ferkingstad, Egil |
dc.contributor.author |
Jensson, Brynjar Ö |
dc.contributor.author |
Stefansson, Hreinn |
dc.contributor.author |
Olafsson, Isleifur |
dc.contributor.author |
Christensen, Alex H |
dc.contributor.author |
Torp-Pedersen, Christian |
dc.contributor.author |
Køber, Lars |
dc.contributor.author |
Pedersen, Ole B |
dc.contributor.author |
Erikstrup, Christian |
dc.contributor.author |
Sørensen, Erik |
dc.contributor.author |
Brunak, Søren |
dc.contributor.author |
Banasik, Karina |
dc.contributor.author |
Hansen, Thomas F |
dc.contributor.author |
Nyegaard, Mette |
dc.contributor.author |
Eyjólfsson, Guðmundur I. |
dc.contributor.author |
Sigurdardottir, Olof |
dc.contributor.author |
Þórarinsson, Björn L |
dc.contributor.author |
Matthíasson, Stefán E. |
dc.contributor.author |
Steingrimsdottir, Thora |
dc.contributor.author |
Björnsson, Einar Stefán |
dc.contributor.author |
Danielsen, Ragnar |
dc.contributor.author |
Asselbergs, Folkert W. |
dc.contributor.author |
Arnar, David O |
dc.contributor.author |
Ullum, Henrik |
dc.contributor.author |
Bundgaard, Henning |
dc.contributor.author |
sulem, patrick |
dc.contributor.author |
Thorsteinsdottir, Unnur |
dc.contributor.author |
Thorgeirsson, Gudmundur |
dc.contributor.author |
Holm, Hilma |
dc.contributor.author |
Gudbjartsson, Daniel |
dc.contributor.author |
Stefansson, Kari |
dc.date.accessioned |
2021-02-02T14:58:40Z |
dc.date.available |
2021-02-02T14:58:40Z |
dc.date.issued |
2020-07-21 |
dc.identifier.citation |
Anna Helgadottir, Gudmar Thorleifsson, Kristjan F Alexandersson, Vinicius Tragante, Margret Thorsteinsdottir, Finnur F Eiriksson, Solveig Gretarsdottir, Eythór Björnsson, Olafur Magnusson, Gardar Sveinbjornsson, Ingileif Jonsdottir, Valgerdur Steinthorsdottir, Egil Ferkingstad, Brynjar Ö Jensson, Hreinn Stefansson, Isleifur Olafsson, Alex H Christensen, Christian Torp-Pedersen, Lars Køber, Ole B Pedersen, Christian Erikstrup, Erik Sørensen, Søren Brunak, Karina Banasik, Thomas F Hansen, Mette Nyegaard, Gudmundur I Eyjolfssson, Olof Sigurdardottir, Bjorn L Thorarinsson, Stefan E Matthiasson, Thora Steingrimsdottir, Einar S Bjornsson, Ragnar Danielsen, Folkert W Asselbergs, David O Arnar, Henrik Ullum, Henning Bundgaard, Patrick Sulem, Unnur Thorsteinsdottir, Gudmundur Thorgeirsson, Hilma Holm, Daniel F Gudbjartsson, Kari Stefansson, Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease, European Heart Journal, Volume 41, Issue 28, 21 July 2020, Pages 2618–2628, https://doi.org/10.1093/eurheartj/ehaa531 |
dc.identifier.issn |
0195-668X |
dc.identifier.issn |
1522-9645 (eISSN) |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/2448 |
dc.description |
Publisher's version (útgefin grein) |
dc.description.abstract |
Aims: To explore whether variability in dietary cholesterol and phytosterol absorption impacts the risk of coronary artery disease (CAD) using as instruments sequence variants in the ABCG5/8 genes, key regulators of intestinal absorption of dietary sterols. Methods and results: We examined the effects of ABCG5/8 variants on non-high-density lipoprotein (non-HDL) cholesterol (N up to 610 532) and phytosterol levels (N = 3039) and the risk of CAD in Iceland, Denmark, and the UK Biobank (105 490 cases and 844 025 controls). We used genetic scores for non-HDL cholesterol to determine whether ABCG5/8 variants confer greater risk of CAD than predicted by their effect on non-HDL cholesterol. We identified nine rare ABCG5/8 coding variants with substantial impact on non-HDL cholesterol. Carriers have elevated phytosterol levels and are at increased risk of CAD. Consistent with impact on ABCG5/8 transporter function in hepatocytes, eight rare ABCG5/8 variants associate with gallstones. A genetic score of ABCG5/8 variants predicting 1 mmol/L increase in non-HDL cholesterol associates with two-fold increase in CAD risk [odds ratio (OR) = 2.01, 95% confidence interval (CI) 1.75-2.31, P = 9.8 × 10-23] compared with a 54% increase in CAD risk (OR = 1.54, 95% CI 1.49-1.59, P = 1.1 × 10-154) associated with a score of other non-HDL cholesterol variants predicting the same increase in non-HDL cholesterol (P for difference in effects = 2.4 × 10-4). Conclusions: Genetic variation in cholesterol absorption affects levels of circulating non-HDL cholesterol and risk of CAD. Our results indicate that both dietary cholesterol and phytosterols contribute directly to atherogenesis. |
dc.description.sponsorship |
This work was supported by deCODE genetics/Amgen. S.B. is supported by the Novo Nordisk Foundation (NNF14CC0001 and NNF17OC0027594). F.W.A. is supported by University College London Hospital National Institute for Health Research Biomedical Research Centre (BRC288A). |
dc.format.extent |
2618-2628 |
dc.language.iso |
en |
dc.publisher |
Oxford University Press (OUP) |
dc.relation.ispartofseries |
European Heart Journal;41(28) |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
ABCG5/8 |
dc.subject |
Absorption |
dc.subject |
Dietary cholesterol |
dc.subject |
Genetics |
dc.subject |
Phytosterols |
dc.subject |
Kólesteról |
dc.subject |
Erfðarannsóknir |
dc.subject |
Kransæðasjúkdómar |
dc.title |
Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease |
dc.type |
info:eu-repo/semantics/article |
dcterms.license |
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
dc.description.version |
Peer Reviewed |
dc.identifier.journal |
European Heart Journal |
dc.identifier.doi |
10.1093/eurheartj/ehaa531 |
dc.relation.url |
https://academic.oup.com/eurheartj/article/41/28/2618/5875424 |
dc.contributor.department |
Læknadeild (HÍ) |
dc.contributor.department |
Faculty of Medicine (UI) |
dc.contributor.school |
Heilbrigðisvísindasvið (HÍ) |
dc.contributor.school |
School of Health Sciences (UI) |
dc.contributor.school |
Verkfræði- og náttúruvísindasvið (HÍ) |
dc.contributor.school |
School of Engineering and Natural Sciences (UI) |