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dc.contributor.authorHelgadottir, Anna
dc.contributor.authorGretarsdottir, Solveig
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorHjartarson, Eirikur
dc.contributor.authorSigurdsson, Asgeir
dc.contributor.authorMagnusdottir, Audur
dc.contributor.authorJonasdottir, Aslaug
dc.contributor.authorKristjansson, Helgi
dc.contributor.authorSulem, Patrick
dc.contributor.authorOddsson, Asmundur
dc.contributor.authorSveinbjornsson, Gardar
dc.contributor.authorSteinthorsdottir, Valgerdur
dc.contributor.authorRafnar, Thorunn
dc.contributor.authorMasson, Gisli
dc.contributor.authorJonsdottir, Ingileif
dc.contributor.authorOlafsson, Isleifur
dc.contributor.authorEyjolfsson, Gudmundur I
dc.contributor.authorSigurdardottir, Olof
dc.contributor.authorDaneshpour, Maryam S
dc.contributor.authorKhalili, Davood
dc.contributor.authorAzizi, Fereidoun
dc.contributor.authorSwinkels, Dorine W
dc.contributor.authorKiemeney, Lambertus
dc.contributor.authorQuyyumi, Arshed A
dc.contributor.authorLevey, Allan I
dc.contributor.authorPatel, Riyaz S
dc.contributor.authorHayek, Salim S
dc.contributor.authorGudmundsdottir, Ingibjorg J
dc.contributor.authorThorgeirsson, Gudmundur
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorGudbjartsson, Daniel F
dc.contributor.authorHolm, Hilma
dc.contributor.authorStefansson, Kari
dc.date.accessioned2016-06-29T15:02:50Z
dc.date.available2016-06-29T15:02:50Z
dc.date.issued2016-05-02
dc.date.submitted2016
dc.identifier.citationVariants with large effects on blood lipids and the role of cholesterol and triglycerides in coronary disease 2016, 48 (6):634 Nature Geneticsen
dc.identifier.issn1061-4036
dc.identifier.issn1546-1718
dc.identifier.doi10.1038/ng.3561
dc.identifier.urihttp://hdl.handle.net/2336/615011
dc.descriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.en
dc.description.abstractSequence variants affecting blood lipids and coronary artery disease (CAD) may enhance understanding of the atherogenicity of lipid fractions. Using a large resource of whole-genome sequence data, we examined rare and low-frequency variants for association with non-HDL cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides in up to 119,146 Icelanders. We discovered 13 variants with large effects (within ANGPTL3, APOB, ABCA1, NR1H3, APOA1, LIPC, CETP, LDLR, and APOC1) and replicated 14 variants. Five variants within PCSK9, APOA1, ANGPTL4, and LDLR associate with CAD (33,090 cases and 236,254 controls). We used genetic risk scores for the lipid fractions to examine their causal relationship with CAD. The non-HDL cholesterol genetic risk score associates most strongly with CAD (P = 2.7 x 10(-28)), and no other genetic risk score associates with CAD after accounting for non-HDL cholesterol. The genetic risk score for non-HDL cholesterol confers CAD risk beyond that of LDL cholesterol (P = 5.5 x 10(-8)), suggesting that targeting atherogenic remnant cholesterol may reduce cardiovascular risk.
dc.description.sponsorshipEmory Neuroscience NINDS Core Facilities grant P30NS055077 deCODE Genetics/Amgen Emory by NIH grants from the Clinical and Translational Science Award program / UL1RR025008 R01HL089650-02en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urlhttp://www.nature.com/doifinder/10.1038/ng.3561en
dc.relation.urlhttp://dx.doi.org/ 10.1038/ng.3561en
dc.relation.urlhttp://www.nature.com/ng/journal/v48/n6/pdf/ng.3561.pdfen
dc.rightsArchived with thanks to Nature Geneticsen
dc.subjectBlóðfitaen
dc.subjectKransæðasjúkdómaren
dc.subjectAAI12
dc.subjectMAB12
dc.subjectCAR12
dc.subject.meshCoronary Artery Disease/blood*en
dc.subject.meshCholesterolen
dc.subject.meshTriglyceridesen
dc.subject.meshCoronary Diseaseen
dc.titleVariants with large effects on blood lipids and the role of cholesterol and triglycerides in coronary diseaseen
dc.typeArticleen
dc.contributor.department[ 1 ] Amgen Inc, deCODE Genet, Reykjavik, Iceland [ 2 ] Univ Iceland, Fac Med, Reykjavik, Iceland [ 3 ] Landspitali Natl Univ Hosp, Dept Immunol, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital [ 4 ] Landspitali Natl Univ Hosp, Dept Clin Biochem, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital [ 5 ] Lab Mjodd RAM, Reykjavik, Iceland [ 6 ] Akureyri Hosp, Dept Clin Biochem, Akureyri, Iceland [ 7 ] Shahid Beheshti Univ Med Sci, Res Inst Endocrine Sci, Cellular & Mol Endocrine Res Ctr, Tehran, Iran [ 8 ] Shahid Beheshti Univ Med Sci, Prevent Metab Disorders Res Ctr, Res Inst Endocrine Sci, Tehran, Iran [ 9 ] Shahid Beheshti Univ Med Sci, Endocrine Res Ctr, Res Inst Endocrine Sci, Tehran, Iran [ 10 ] Radboud Univ Nijmegen, Dept Lab Med, Med Ctr, Radboud Inst Mol Life Sci, NL-6525 ED Nijmegen, Netherlands [ 11 ] Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Med Ctr, NL-6525 ED Nijmegen, Netherlands [ 12 ] Emory Univ, Sch Med, Atlanta, GA USA [ 13 ] Landspitali Natl Univ Hosp, Dept Internal Med, Div Cardiol, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital [ 14 ] Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Icelanden
dc.identifier.journalNature Geneticsen
dc.rights.accessLandspitali Access - LSH-aðganguren
html.description.abstractSequence variants affecting blood lipids and coronary artery disease (CAD) may enhance understanding of the atherogenicity of lipid fractions. Using a large resource of whole-genome sequence data, we examined rare and low-frequency variants for association with non-HDL cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides in up to 119,146 Icelanders. We discovered 13 variants with large effects (within ANGPTL3, APOB, ABCA1, NR1H3, APOA1, LIPC, CETP, LDLR, and APOC1) and replicated 14 variants. Five variants within PCSK9, APOA1, ANGPTL4, and LDLR associate with CAD (33,090 cases and 236,254 controls). We used genetic risk scores for the lipid fractions to examine their causal relationship with CAD. The non-HDL cholesterol genetic risk score associates most strongly with CAD (P = 2.7 x 10(-28)), and no other genetic risk score associates with CAD after accounting for non-HDL cholesterol. The genetic risk score for non-HDL cholesterol confers CAD risk beyond that of LDL cholesterol (P = 5.5 x 10(-8)), suggesting that targeting atherogenic remnant cholesterol may reduce cardiovascular risk.


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