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Exome-wide association study of plasma lipids in > 300,000 individuals
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2017 (engelsk)Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, nr 12, s. 1758-1766Artikkel i tidsskrift, Letter (Fagfellevurdert) Published
Abstract [en]

We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-densitylipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.

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NATURE PUBLISHING GROUP , 2017. Vol. 49, nr 12, s. 1758-1766
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URN: urn:nbn:se:umu:diva-143009DOI: 10.1038/ng.3977ISI: 000416480600016OAI: oai:DiVA.org:umu-143009DiVA, id: diva2:1166270
Tilgjengelig fra: 2017-12-14 Laget: 2017-12-14 Sist oppdatert: 2018-06-09bibliografisk kontrollert

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