Abstract
Exposures to copper have become a health concern. We aim to explore the broad clinical effects of blood copper concentrations. A total of 376,346 Caucasian subjects were enrolled. We performed a Mendelian randomization and phenome-wide association study (MR-PheWAS) to evaluate the causal association between copper and a wide range of outcomes in UK Biobank, and we constructed a protein–protein interaction network. We found association between blood copper concentrations and five diseases in the overall population and nine diseases in male. MR analysis implicated a causal role of blood copper in five diseases (overall population), including prostate cancer (OR = 0.87, 95% CI 0.77–0.98), malignant and unknown neoplasms of the brain and nervous system (OR = 0.58, 95% CI 0.38–0.89), and hypertension (OR = 0.94, 95% CI 0.90–0.98), essential hypertension (OR = 0.94, 95% CI 0.90–0.98) and cancer of brain and nervous system (OR = 0.63, 95% CI 0.41–0.98). For male, except for dysphagia being newly associated with blood copper (OR = 1.39, 95% CI 1.18–1.63), other MR results were consistent with the overall population. In addition, the PPI network showed possible relationship between blood copper and four outcomes, namely brain cancer, prostate cancer, hypertension, and dysphagia. Blood copper may have causal association with prostate cancer, malignant and unknown neoplasms of the brain and nervous system, hypertension, and dysphagia. Considering that copper is modifiable, exploring whether regulation of copper levels can be used to optimize health outcomes might have public health importance.
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The genetic and phenotypic UK Biobank data are available upon application from the UK Biobank (www.ukbiobank.ac.uk/).
Code availability
The code that support the findings of this study are available from the corresponding author upon reasonable request.
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The authors acknowledge the UK Biobank and their participants for contributing the data used in this work (approval number: 56902). This work was supported by the National Key R&D Program of China (grant number 2020YFE0201600); the National Natural Science Foundation of China (grant number 82073504); the Guangxi Natural Science Fund for Innovation Research Team (grant number 2017GXNSFGA198003).
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Conceptualization, data curation and funding acquisition: XY and ZM. Original draft and formal analysis: XF, WY and LH. Methodology: LL and LH. Software: HC and XG. Visualization: GZ and YT. Review and editing: LX and CL. Validation: XC.
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UK Biobank received ethical approval from the research ethics committee (reference 13/NW/0382). All participants provided informed consent to participate. The present analyses were conducted under UK Biobank application number 56902.
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Feng, X., Yang, W., Huang, L. et al. Causal Effect of Genetically Determined Blood Copper Concentrations on Multiple Diseases: A Mendelian Randomization and Phenome-Wide Association Study. Phenomics 2, 242–253 (2022). https://doi.org/10.1007/s43657-022-00052-3
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DOI: https://doi.org/10.1007/s43657-022-00052-3