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Liu, D.J.* ; Peloso, G.M.* ; Yu, H.* ; Butterworth, A.S.* ; Wang, X.* ; Mahajan, A.* ; Saleheen, D.* ; Emdin, C.* ; Alam, D.* ; Alves, A.C.* ; Amouyel, P.* ; Angelantonio, E.D.* ; Arveiler, D.* ; Assimes, T.L.* ; Auer, P.L.* ; Baber, U.* ; Ballantyne, C.M.* ; Bang, L.E.* ; Benn, M.* ; Bis, J.C.* ; Boehnke, M.* ; Boerwinkle, E.* ; Bork-Jensen, J.* ; Bottinger, E.P.* ; Brandslund, I.* ; Brown, M.* ; Busonero, F.* ; Caulfield, M.J.* ; Chambers, J.C.* ; Chasman, D.I.* ; Chen, Y.E.* ; Chen, Y.D.I.* ; Chowdhury, R.* ; Christensen, C.* ; Chu, A.Y.* ; Connell, J.M.* ; Cucca, F.* ; Cupples, L.A.* ; Damrauer, S.M.* ; Davies, G.* ; Deary, I.J.* ; Dedoussis, G.* ; Denny, J.C.* ; Dominiczak, A.* ; Dubé, M.-P.* ; Strauch, K. ; Waldenberger, M. ; Kathiresan, S.* ; Farmaki, A.-E.* ; Feitosa, M.F.* ; Ferrario, M.* ; Ferrieres, J.* ; Ford, I.* ; Fornage, M.* ; Franks, P.W.* ; Frayling, T.M.* ; Frikke-Schmidt, R.* ; Fritsche, L.G.* ; Frossard, P.* ; Fuster, V.* ; Ganesh, S.K.* ; Gao, W.* ; Garcia, M.E.* ; Gieger, C. ; Giulianini, F.* ; Goodarzi, M.O.* ; Grallert, H. ; Müller-Nurasyid, M. ; Peters, A.

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

Nat. Genet. 49, 1758-1766 (2017)
Postprint DOI PMC
Open Access Green
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 TGrich 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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 49, Issue: 12, Pages: 1758-1766 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology II (EPI2)
CCG Biomarker for the subclassification of T2DM (KKG-KDB)