Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease

Almenn færsla
dc.contributorHáskóli Íslandsen_US
dc.contributorUniversity of Icelanden_US
dc.contributor.authorHelgadottir, Anna
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorAlexandersson, Kristjan F
dc.contributor.authorTragante, Vinicius
dc.contributor.authorÞorsteinsdóttir, Margrét
dc.contributor.authorEiriksson, Finnur Freyr
dc.contributor.authorGrétarsdóttir, Sólveig
dc.contributor.authorBjörnsson, Eyþór
dc.contributor.authorMagnússon, Ólafur
dc.contributor.authorSveinbjornsson, Gardar
dc.contributor.authorJonsdottir, Ingileif
dc.contributor.authorSteinthorsdottir, Valgerdur
dc.contributor.authorFerkingstad, Egil
dc.contributor.authorJensson, Brynjar Ö
dc.contributor.authorStefansson, Hreinn
dc.contributor.authorOlafsson, Isleifur
dc.contributor.authorChristensen, Alex H
dc.contributor.authorTorp-Pedersen, Christian
dc.contributor.authorKøber, Lars
dc.contributor.authorPedersen, Ole B
dc.contributor.authorErikstrup, Christian
dc.contributor.authorSørensen, Erik
dc.contributor.authorBrunak, Søren
dc.contributor.authorBanasik, Karina
dc.contributor.authorHansen, Thomas F
dc.contributor.authorNyegaard, Mette
dc.contributor.authorEyjólfsson, Guðmundur I.
dc.contributor.authorSigurdardottir, Olof
dc.contributor.authorÞórarinsson, Björn L
dc.contributor.authorMatthíasson, Stefán E.
dc.contributor.authorSteingrimsdottir, Thora
dc.contributor.authorBjörnsson, Einar Stefán
dc.contributor.authorDanielsen, Ragnar
dc.contributor.authorAsselbergs, Folkert W.
dc.contributor.authorArnar, David O
dc.contributor.authorUllum, Henrik
dc.contributor.authorBundgaard, Henning
dc.contributor.authorsulem, patrick
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorThorgeirsson, Gudmundur
dc.contributor.authorHolm, Hilma
dc.contributor.authorGudbjartsson, Daniel
dc.contributor.authorStefansson, Kari
dc.contributor.departmentLæknadeild (HÍ)en_US
dc.contributor.departmentFaculty of Medicine (UI)en_US
dc.contributor.schoolHeilbrigðisvísindasvið (HÍ)en_US
dc.contributor.schoolSchool of Health Sciences (UI)en_US
dc.contributor.schoolVerkfræði- og náttúruvísindasvið (HÍ)en_US
dc.contributor.schoolSchool of Engineering and Natural Sciences (UI)en_US
dc.date.accessioned2021-02-02T14:58:40Z
dc.date.available2021-02-02T14:58:40Z
dc.date.issued2020-07-21
dc.descriptionPublisher's version (útgefin grein)en_US
dc.description.abstractAims: 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.en_US
dc.description.sponsorshipThis 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).en_US
dc.description.versionPeer Revieweden_US
dc.format.extent2618-2628en_US
dc.identifier.citationAnna 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/ehaa531en_US
dc.identifier.doi10.1093/eurheartj/ehaa531
dc.identifier.issn0195-668X
dc.identifier.issn1522-9645 (eISSN)
dc.identifier.journalEuropean Heart Journalen_US
dc.identifier.urihttps://hdl.handle.net/20.500.11815/2448
dc.language.isoenen_US
dc.publisherOxford University Press (OUP)en_US
dc.relation.ispartofseriesEuropean Heart Journal;41(28)
dc.relation.urlhttps://academic.oup.com/eurheartj/article/41/28/2618/5875424en_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectABCG5/8en_US
dc.subjectAbsorptionen_US
dc.subjectDietary cholesterolen_US
dc.subjectGeneticsen_US
dc.subjectPhytosterolsen_US
dc.subjectKólesterólen_US
dc.subjectErfðarannsókniren_US
dc.subjectKransæðasjúkdómaren_US
dc.titleGenetic variability in the absorption of dietary sterols affects the risk of coronary artery diseaseen_US
dc.typeinfo:eu-repo/semantics/articleen_US
dcterms.licenseThis 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.comen_US

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