Liu, DJ;
Peloso, GM;
Yu, H;
Butterworth, AS;
Wang, X;
Mahajan, A;
Saleheen, D;
... Kathiresan, S; + view all
(2017)
Exome-wide association study of plasma lipids in > 300,000 individuals.
Nature Genetics
, 49
(12)
pp. 1758-1766.
10.1038/ng.3977.
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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-density-lipoprotein 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.
| Type: | Article |
|---|---|
| Title: | Exome-wide association study of plasma lipids in > 300,000 individuals |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ng.3977 |
| Publisher version: | http://doi.org/10.1038/ng.3977 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10065427 |
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