PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study.
- Schmidt, A.F.
- Swerdlow, D.I.
- Holmes, M.V.
- Patel, R.S.
- Fairhurst-Hunter, Z.
- Lyall, D.M.
- Hartwig, F.P.
- Horta, B.L.
- Hyppönen, E.
- Power, C.
- Moldovan, M.
- van Iperen, E.
- Hovingh, G.K.
- Demuth, I.
- Norman, K.
- Steinhagen-Thiessen, E.
- Demuth, J.
- Bertram, L.
- Liu, T.
- Coassin, S.
- Willeit, J.
- Kiechl, S.
- Willeit, K.
- Mason, D.
- Wright, J.
- Morris, R.
- Wanamethee, G.
- Whincup, P.
- Ben-Shlomo, Y.
- McLachlan, S.
- Price, J.F.
- Kivimaki, M.
- Welch, C.
- Sanchez-Galvez, A.
- Marques-Vidal, P.
- Nicolaides, A.
- Panayiotou, A.G.
- Onland-Moret, N.C.
- van der Schouw, Y.T.
- Matullo, G.
- Fiorito, G.
- Guarrera, S.
- Sacerdote, C.
- Wareham, N.J.
- Langenberg, C.
- Scott, R.
- Luan, J.
- Bobak, M.
- Malyutina, S.
- Pająk, A.
- Kubinova, R.
- Tamosiunas, A.
- Pikhart, H.
- Husemoen, L.L.
- Grarup, N.
- Pedersen, O.
- Hansen, T.
- Linneberg, A.
- Simonsen, K.S.
- Cooper, J.
- Humphries, S.E.
- Brilliant, M.
- Kitchner, T.
- Hakonarson, H.
- Carrell, D.S.
- McCarty, C.A.
- Kirchner, H.L.
- Larson, E.B.
- Crosslin, D.R.
- de Andrade, M.
- Roden, D.M.
- Denny, J.C.
- Carty, C.
- Hancock, S.
- Attia, J.
- Holliday, E.
- O'Donnell, M.
- Yusuf, S.
- Chong, M.
- Pare, G.
- van der Harst, P.
- Said, M.A.
- Eppinga, R.N.
- Verweij, N.
- Snieder, H.
- Christen, T.
- Mook-Kanamori, D.O.
- Gustafsson, S.
- Lind, L.
- Ingelsson, E.
- Pazoki, R.
- Franco, O.
- Hofman, A.
- Uitterlinden, A.
- Dehghan, A.
- Teumer, A.
- Baumeister, S.
- Dörr, M.
- Lerch, M.M.
- Völker, U.
- Völzke, H.
- Ward, J.
- Pell, J.P.
- Smith, D.J.
- Meade, T.
- Maitland-van der Zee, A.H.
- Baranova, E.V.
- Young, R.
- Ford, I.
- Campbell, A.
- Padmanabhan, S.
- Bots, M.L.
- Grobbee, D.E.
- Froguel, P.
- Thuillier, D.
- Balkau, B.
- Bonnefond, A.
- Cariou, B.
- Smart, M.
- Bao, Y.
- Kumari, M.
- Mahajan, A.
- Ridker, P.M.
- Chasman, D.I.
- Reiner, A.P.
- Lange, L.A.
- Ritchie, M.D.
- Asselbergs, F.W.
- Casas, J.P.
- Keating, B.J.
- Preiss, D.
- Hingorani, A.D.
- Sattar, N.
DOIAbstract
Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL chol...
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