| Literature DB >> 27135400 |
Anna Helgadottir1,2, Solveig Gretarsdottir1, Gudmar Thorleifsson1, Eirikur Hjartarson1, Asgeir Sigurdsson1, Audur Magnusdottir1, Aslaug Jonasdottir1, Helgi Kristjansson1, Patrick Sulem1, Asmundur Oddsson1, Gardar Sveinbjornsson1, Valgerdur Steinthorsdottir1, Thorunn Rafnar1, Gisli Masson1, Ingileif Jonsdottir1,2,3, Isleifur Olafsson4, Gudmundur I Eyjolfsson5, Olof Sigurdardottir6, Maryam S Daneshpour7, Davood Khalili8, Fereidoun Azizi9, Dorine W Swinkels10, Lambertus Kiemeney11, Arshed A Quyyumi12, Allan I Levey12, Riyaz S Patel12, Salim S Hayek12, Ingibjorg J Gudmundsdottir13, Gudmundur Thorgeirsson2,13, Unnur Thorsteinsdottir1,2, Daniel F Gudbjartsson1,14, Hilma Holm1,13, Kari Stefansson1,2.
Abstract
Sequence 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 × 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 × 10(-8)), suggesting that targeting atherogenic remnant cholesterol may reduce cardiovascular risk.Entities:
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Year: 2016 PMID： 27135400 PMCID： PMC9136713 DOI： 10.1038/ng.3561
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 41.307