Blood copper and risk of cardiometabolic diseases: a Mendelian randomization study.
Hum Mol Genet
; 31(5): 783-791, 2022 03 03.
Article
em En
| MEDLINE
| ID: mdl-34523676
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Doença da Artéria Coronariana
/
Doenças Cardiovasculares
/
Diabetes Mellitus Tipo 2
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Observational_studies
/
Prognostic_studies
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Risk_factors_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
Hum Mol Genet
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Alemanha