dc.contributor.author | Eiríksson, Finnur Freyr |
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 | Grétarsdóttir, Solveig |
dc.contributor.author | Björnsson, Eyþór |
dc.contributor.author | Magnússon, Ólafur |
dc.contributor.author | Sveinbjornsson, Gardar |
dc.contributor.author | Jónsdóttir, 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 | Ólafsson, Ísleifur |
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 | Sorensen, Erik |
dc.contributor.author | Brunak, Søren |
dc.contributor.author | Banasik, Karina |
dc.contributor.author | Hansen, Thomas Folkmann |
dc.contributor.author | Nyegaard, Mette |
dc.contributor.author | Eyjolfssson, Gudmundur I |
dc.contributor.author | Sigurdardottir, Olof |
dc.contributor.author | Thorarinsson, Bjorn L |
dc.contributor.author | Matthiasson, Stefan E. |
dc.contributor.author | Steingrimsdottir, Thora |
dc.contributor.author | Bjornsson, Einar S |
dc.contributor.author | Danielsen, Ragnar |
dc.contributor.author | Asselbergs, Folkert W |
dc.contributor.author | Arnar, Davíð Ottó |
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 F |
dc.contributor.author | Stefansson, Kari |
dc.date.accessioned | 2023-02-25T01:06:02Z |
dc.date.available | 2023-02-25T01:06:02Z |
dc.date.issued | 2020 |
dc.identifier.citation | Eiríksson , F F , Helgadottir , A , Thorleifsson , G , Alexandersson , K F , Tragante , V , Þorsteinsdóttir , M , Grétarsdóttir , S , Björnsson , E , Magnússon , Ó , Sveinbjornsson , G , Jónsdóttir , I , Steinthorsdottir , V , Ferkingstad , E , Jensson , B Ö , Stefansson , H , Ólafsson , Í , Christensen , A H , Torp-Pedersen , C , Køber , L , Pedersen , O B , Erikstrup , C , Sorensen , E , Brunak , S , Banasik , K , Hansen , T F , Nyegaard , M , Eyjolfssson , G I , Sigurdardottir , O , Thorarinsson , B L , Matthiasson , S E , Steingrimsdottir , T , Bjornsson , E S , Danielsen , R , Asselbergs , F W , Arnar , D O , Ullum , H , Bundgaard , H , sulem , P , Thorsteinsdottir , U , Thorgeirsson , G , Holm , H , Gudbjartsson , D F & Stefansson , K 2020 , ' Genetic variability in the uptake of dietary sterols affects the risk of coronary artery disease ' , European Heart Journal , vol. 41 , no. 28 . https://doi.org/10.1093/eurheartj/ehaa531 |
dc.identifier.issn | 0195-668X |
dc.identifier.other | 70591466 |
dc.identifier.other | 7a907fbe-ce36-43c0-b8ad-0e866c592935 |
dc.identifier.uri | https://hdl.handle.net/20.500.11815/4033 |
dc.description | 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). Conflict of interest: The authors affiliated with deCODE genetics/Amgen, Inc. are employed by the company. |
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.format.extent | 4889378 |
dc.format.extent | |
dc.language.iso | en |
dc.relation.ispartofseries | European Heart Journal; 41(28) |
dc.rights | info:eu-repo/semantics/openAccess |
dc.title | Genetic variability in the uptake of dietary sterols affects the risk of coronary artery disease |
dc.type | /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article |
dc.description.version | Peer reviewed |
dc.identifier.doi | https://doi.org/10.1093/eurheartj/ehaa531 |
dc.contributor.department | Faculty of Pharmaceutical Sciences |
dc.contributor.department | Clinical Laboratory Services, Diagnostics and Blood Bank |
dc.contributor.department | Faculty of Medicine |
dc.contributor.department | Other departments |
dc.contributor.school | Health Sciences |