{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:29:18Z","timestamp":1793104158747,"version":"4.5.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"28","license":[{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF14CC0001"],"award-info":[{"award-number":["NNF14CC0001"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF17OC0027594"],"award-info":[{"award-number":["NNF17OC0027594"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University College London Hospital National Institute for Health Research Biomedical Research Centre","award":["BRC288A"],"award-info":[{"award-number":["BRC288A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We examined the effects of ABCG5\/8 variants on non-high-density lipoprotein (non-HDL) cholesterol (N up to 610\u00a0532) and phytosterol levels (N\u2009=\u20093039) and the risk of CAD in Iceland, Denmark, and the UK Biobank (105\u00a0490 cases and 844\u00a0025 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\u2009mmol\/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\u20132.31, P\u2009=\u20099.8\u2009\u00d7\u200910\u221223] compared with a 54% increase in CAD risk (OR = 1.54, 95% CI 1.49\u20131.59, P\u2009=\u20091.1\u2009\u00d7\u200910\u2212154) 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\u2009\u00d7\u200910\u22124).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p\/>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehaa531","type":"journal-article","created":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T11:07:08Z","timestamp":1591614428000},"page":"2618-2628","source":"Crossref","is-referenced-by-count":86,"title":["Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1806-2467","authenticated-orcid":false,"given":"Anna","family":"Helgadottir","sequence":"first","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4623-9087","authenticated-orcid":false,"given":"Gudmar","family":"Thorleifsson","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5558-4563","authenticated-orcid":false,"given":"Kristjan F","family":"Alexandersson","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8223-8957","authenticated-orcid":false,"given":"Vinicius","family":"Tragante","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"},{"name":"Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University , 3584 CX Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0649-8503","authenticated-orcid":false,"given":"Margret","family":"Thorsteinsdottir","sequence":"additional","affiliation":[{"name":"ArcticMass , Sturlugata 8, 102 Reykjavik, Iceland"},{"name":"Faculty of Pharmaceutical Sciences, University of Iceland , Hofsvallagata 53, 107 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finnur F","family":"Eiriksson","sequence":"additional","affiliation":[{"name":"ArcticMass , Sturlugata 8, 102 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solveig","family":"Gretarsdottir","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyth\u00f3r","family":"Bj\u00f6rnsson","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"},{"name":"Department of Internal Medicine, Landspitali \u2013 National University Hospital of Iceland , 101 Reykjavik, Iceland"},{"name":"Faculty of Medicine, University of Iceland , Vatnsm\u00fdrarvegur, 101 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olafur","family":"Magnusson","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gardar","family":"Sveinbjornsson","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8339-150X","authenticated-orcid":false,"given":"Ingileif","family":"Jonsdottir","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"},{"name":"Faculty of Medicine, University of Iceland , Vatnsm\u00fdrarvegur, 101 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1846-6274","authenticated-orcid":false,"given":"Valgerdur","family":"Steinthorsdottir","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8090-7988","authenticated-orcid":false,"given":"Egil","family":"Ferkingstad","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brynjar \u00d6","family":"Jensson","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9331-6666","authenticated-orcid":false,"given":"Hreinn","family":"Stefansson","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isleifur","family":"Olafsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Landspitali \u2013National University Hospital of Iceland , Hringbraut, 101 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex H","family":"Christensen","sequence":"additional","affiliation":[{"name":"Herlev-Gentofte Hospital, Copenhagen University Hospital , Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Torp-Pedersen","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Clinical Research, Nordsjaellands Hospital , Dyrehavevej 29, 3400 Hiller\u00f8d, Denmark"},{"name":"Department of Cardiology, Aalborg University Hospital , Hobrovej 18-22, 9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"K\u00f8ber","sequence":"additional","affiliation":[{"name":"The Capital Region\u2019s Unit of Inherited Cardiac Diseases, Department of Cardiology, The Heart Centre, Copenhagen University Hospital , Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2312-5976","authenticated-orcid":false,"given":"Ole B","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, N\u00e6stved Hospital , Ringstedgade 61, 4700 N\u00e6stved, Denmark"},{"name":"Department of Clinical Medicine, Copenhagen University , Blegdamsvej 3B, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6551-6647","authenticated-orcid":false,"given":"Christian","family":"Erikstrup","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Aarhus University Hospital , Palle Juul-Jensens Boulevard 99, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital , Blegdamsvej 9, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren","family":"Brunak","sequence":"additional","affiliation":[{"name":"Translational Disease Systems Biology, Novo Nordisk Foundation Center 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Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Bundgaard","sequence":"additional","affiliation":[{"name":"The Capital Region\u2019s Unit of Inherited Cardiac Diseases, Department of Cardiology, The Heart Centre, Copenhagen University Hospital , Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7123-6123","authenticated-orcid":false,"given":"Patrick","family":"Sulem","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unnur","family":"Thorsteinsdottir","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen, Inc. , Sturlugata 8, 102 Reykjavik, Iceland"},{"name":"Faculty of Medicine, University of Iceland , Vatnsm\u00fdrarvegur, 101 Reykjavik, 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