학술논문
Complex effects of sequence variants on lipid levels and coronary artery disease.
Document Type
Academic Journal
Author
Snaebjarnarson AS; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland.; Helgadottir A; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland.; Arnadottir GA; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland.; Ivarsdottir EV; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland.; Thorleifsson G; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland.; Ferkingstad E; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland.; Einarsson G; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland.; Sveinbjornsson G; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland.; Thorgeirsson TE; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland.; Ulfarsson MO; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland; Faculty of Electrical and Computer Engineering, University of Iceland, Reykjavik 102, Iceland.; Halldorsson BV; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland.; Olafsson I; Department of Clinical Biochemistry, Landspitali - National University Hospital of Iceland, Hringbraut, Reykjavik 101, Iceland.; Erikstrup C; Department of Clinical Immunology, Aarhus University Hospital, Aarhus 8200, Denmark; Department of Clinical Medicine, Health, Aarhus University, Aarhus 8200, Denmark.; Pedersen OB; Department of Clinical Immunology, Zealand University Hospital, Køge 4600, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen 1165, Denmark.; Nyegaard M; Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg 9220, Denmark.; Bruun MT; Department of Clinical Immunology, Odense University Hospital, Odense 5000, Denmark.; Ullum H; Statens Serum Institut, Copenhagen 2300, Denmark.; Brunak S; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.; Iversen KK; Department of Clinical Medicine, University of Copenhagen, Copenhagen 1165, Denmark; Department of Emergency Medicine, Copenhagen University Hospital Herlev and Gentofte, Herlev 2900, Denmark; Department of Cardiology, Copenhagen University Hospital, Herlev-Gentofte Hospital, Herlev 2900, Denmark.; Christensen AH; Department of Clinical Medicine, University of Copenhagen, Copenhagen 1165, Denmark; Department of Cardiology, Copenhagen University Hospital, Herlev-Gentofte Hospital, Herlev 2900, Denmark.; Olesen MS; Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen 2100, Denmark; Laboratory for Molecular Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen 1165, Denmark.; Ghouse J; Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen 2100, Denmark; Laboratory for Molecular Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen 1165, Denmark.; Banasik K; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.; Knowlton KU; Intermountain Medical Center, Intermountain Heart Institute, Salt Lake City, UT 84143, USA.; Arnar DO; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland; Faculty of Medicine, University of Iceland, Vatnsmyrarvegur, Reykjavik 101, Iceland; Division of Cardiology, Department of Internal Medicine, Landspitali - National University Hospital of Iceland, Hringbraut, Reykjavik 101, Iceland.; Thorgeirsson G; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland; Faculty of Medicine, University of Iceland, Vatnsmyrarvegur, Reykjavik 101, Iceland; Division of Cardiology, Department of Internal Medicine, Landspitali - National University Hospital of Iceland, Hringbraut, Reykjavik 101, Iceland.; Nadauld L; Precision Genomics, Intermountain Healthcare, Saint George, UT 84790, USA.; Ostrowski SR; Department of Clinical Medicine, University of Copenhagen, Copenhagen 1165, Denmark; Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark.; Bundgaard H; Department of Clinical Medicine, University of Copenhagen, Copenhagen 1165, Denmark; Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen 2100, Denmark.; Holm H; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland.; Sulem P; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland.; Stefansson K; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland; Faculty of Medicine, University of Iceland, Vatnsmyrarvegur, Reykjavik 101, Iceland. Electronic address: kstefans@decode.is.; Gudbjartsson DF; deCODE genetics/Amgen, Inc., Reykjavik 102, Iceland; School of Engineering and Natural Sciences, University of Iceland, Reykjavik 102, Iceland. Electronic address: daniel.gudbjartsson@decode.is.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE
Subject
Language
English
Abstract
Many sequence variants have additive effects on blood lipid levels and, through that, on the risk of coronary artery disease (CAD). We show that variants also have non-additive effects and interact to affect lipid levels as well as affecting variance and correlations. Variance and correlation effects are often signatures of epistasis or gene-environmental interactions. These complex effects can translate into CAD risk. For example, Trp154Ter in FUT2 protects against CAD among subjects with the A1 blood group, whereas it associates with greater risk of CAD in others. His48Arg in ADH1B interacts with alcohol consumption to affect lipid levels and CAD. The effect of variants in TM6SF2 on blood lipids is greatest among those who never eat oily fish but absent from those who often do. This work demonstrates that variants that affect variance of quantitative traits can allow for the discovery of epistasis and interactions of variants with the environment.
Competing Interests: Declaration of interests The authors affiliated with deCODE genetics/Amgen, Inc. are employed by the company.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of interests The authors affiliated with deCODE genetics/Amgen, Inc. are employed by the company.
(Copyright © 2023 Elsevier Inc. All rights reserved.)