Exome-wide association study of plasma lipids in > 300,000 individuals

Liu, Dajiang J.; Peloso, Gina M.; Yu, Haojie; Müller-Nurasyid, Martina; Strauch, Konstantin; Peters, Annette und Waldenberger, Melanie (2017): Exome-wide association study of plasma lipids in > 300,000 individuals. In: Nature Genetics, Bd. 49, Nr. 12: S. 1758-1766

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1061-4036
• Bemerkung: Weitere Autoren siehe PDF-Volltext
• Sprache: Englisch