Blood copper and risk of cardiometabolic diseases: a Mendelian randomization study.

Autor:	Jäger S; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal 14558, Germany.; German Center for Diabetes Research (DZD), Neuherberg 85764, Germany.; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena, Germany., Cabral M; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal 14558, Germany.; German Center for Diabetes Research (DZD), Neuherberg 85764, Germany.; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena, Germany., Kopp JF; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena, Germany.; Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Nuthetal 14558, Germany., Hoffmann P; Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel 4031, Switzerland.; Division of Genomics, Life and Brain Research Centre, Institute of Human Genetics, University Hospital of Bonn, Bonn 53105, Germany., Ng E; Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK., Whitfield JB; QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia., Morris AP; Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester M13 9PL, UK., Lind L; Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala 75185, Sweden., Schwerdtle T; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena, Germany.; Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Nuthetal 14558, Germany.; Department Food Safety, German Federal Institute for Risk Assessment (BfR), Berlin 10589, Germany., Schulze MB; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal 14558, Germany.; German Center for Diabetes Research (DZD), Neuherberg 85764, Germany.; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena, Germany.; Institute of Nutritional Science, University of Potsdam, Nuthetal 14558, Germany.
Jazyk:	angličtina
Zdroj:	Human molecular genetics [Hum Mol Genet] 2022 Mar 03; Vol. 31 (5), pp. 783-791.
DOI:	10.1093/hmg/ddab275
Abstrakt:	Observational evidence links higher blood levels of copper with higher risk of cardiovascular diseases. However, whether those associations reflect causal links or can be attributed to confounding is still not fully clear. We investigated causal effects of copper on the risk of cardiometabolic endpoints (stroke, coronary artery disease [CAD] and type 2 diabetes) and cardiometabolic risk factors in two-sample Mendelian randomization (MR) studies. The selection of genetic instruments for blood copper levels relied on meta-analysis of genome-wide association studies in three independent studies (European Prospective Investigation into Cancer and Nutrition-Potsdam study, Prospective investigation of the Vasculature in Uppsala Seniors study, Queensland Institute of Medical Research studies). For the selected instruments, outcome associations were drawn from large public genetic consortia on the respective disease endpoints (MEGASTROKE, Cardiogram, DIAGRAM) and cardiometabolic risk factors. MR results indicate an inverse association for genetically higher copper levels with risk of CAD (odds ratio [95% confidence interval] = 0.92 [0.86-0.99], P = 0.022) and systolic blood pressure (beta [standard error (SE)] = -0.238 [0.121]; P = 0.049). Multivariable MR incorporating copper and systolic blood pressure into one model suggested systolic blood pressure as mediating factor between copper and CAD risk. In contrast to previous observational evidence establishing higher blood copper levels as risk-increasing factor for cardiometabolic diseases, this study suggests that higher levels of genetically predicted copper might play a protective role for the development of CAD and systolic blood pressure. (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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