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Genetically Predicted Circulating Copper and Risk of Chronic Kidney Disease: A Mendelian Randomization Study.

ABSTRACT: Elevated circulating copper levels have been associated with chronic kidney disease (CKD), kidney damage, and decline in kidney function. Using a two sample Mendelian randomization approach where copper-associated genetic variants were used as instrumental variables, genetically predicted higher circulating copper levels were associated with higher CKD prevalence (odds ratio 1.17; 95% confidence interval 1.04, 1.32; p-value = 0.009). There was suggestive evidence that genetically predicted higher copper was associated with a lower estimated glomerular filtration rate and a more rapid kidney damage decline. In conclusion, we observed that elevated circulating copper levels may be a causal risk factor for CKD.

SUBMITTER: Ahmad S

PROVIDER: S-EPMC8840411 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Genetically Predicted Circulating Copper and Risk of Chronic Kidney Disease: A Mendelian Randomization Study.

Ahmad Shafqat S Ärnlöv Johan J Larsson Susanna C SC

Nutrients 20220125 3

Elevated circulating copper levels have been associated with chronic kidney disease (CKD), kidney damage, and decline in kidney function. Using a two sample Mendelian randomization approach where copper-associated genetic variants were used as instrumental variables, genetically predicted higher circulating copper levels were associated with higher CKD prevalence (odds ratio 1.17; 95% confidence interval 1.04, 1.32; <i>p</i>-value = 0.009). There was suggestive evidence that genetically predicte ...[more]

PMID: 35276868

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Project description:Background: It is not clarified whether the elevation of adiponectin is the results of kidney damage, or the cause of kidney function injury. To explore the causal association of adiponectin on estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD), this study was performed. Materials and methods: The genetic association of adiponectin were retrieved from one genome-wide association studies with 39,883 participants. The summary-level statistics regarding the eGFR (133,413 participants) and CKD (12,385 CKD cases and 104,780 controls) were retrieved from the CKDGen consortium in the European ancestry. Single-variable Mendelian randomization (MR), bilateral and multivariable MR analyses were used to verify the causal association between adiponectin, eGFR, and CKD. Results: Genetically predicted adiponectin reduces the risk of CKD (OR = 0.71, 95% CI = 0.57-0.89, p = 0.002) and increases the eGFR (β = 0.014, 95% CI = 0.001-0.026, p = 0.034) by the inverse variance weighting (IVW) estimator. These findings remain consistent in the sensitivity analyses. No heterogeneity and pleiotropy were detected in this study (P for MR-Egger 0.617, P for global test > 0.05, and P for Cochran's Q statistics = 0.617). The bilateral MR identified no causal association of CKD on adiponectin (OR = 1.01, 95% CI = 0.96-1.07, p = 0.658), nor did it support the association of eGFR on adiponectin (OR = 0.86, 95% CI = 0.68-1.09, p = 0.207) by the IVW estimator. All the sensitivity analyses reported similar findings (p > 0.05). Additionally, after adjusting for cigarette consumption, alcohol consumption, body mass index, low density lipoprotein, and total cholesterol, the ORs for CKD are 0.70 (95% CI = 0.55-0.90, p = 0.005), 0.75 (95% CI = 0.58-0.97, p = 0.027), 0.82 (95% CI = 0.68-0.99, p = 0.039), 0.74 (95% CI = 0.59-0.93, p = 0.011), and 0.79 (95% CI = 0.61-0.95, p = 0.018), respectively. Conclusion: Using genetic data, this study provides novel causal evidence that adiponectin can protect the kidney function and further reduce the risk of CKD.

Project description:Objective: Inflammatory cytokines disturbance is the main result of immune dysregulation, which is widely described in major depressive disorder (MDD). However, the potential causal relationship between these two factors has not been discovered. Therefore, the purpose of this study was to investigate the causal relationship between inflammatory cytokines and MDD risk by using the two-sample Mendelian randomization (MR) analysis. Method: Two genetic instruments obtained from publicly available gene profile data were utilized for the analysis. We obtained the genetic variation data of 41 inflammatory cytokines from genome-wide association studies (GWAS) meta-analysis of 8293 individuals of Finnish descent. The MDD data, including 135,458 MDD cases and 344,901 controls, were obtained from the Psychiatric Genomics Consortium Database. For the Mendelian randomization (MR) estimation, several methods were employed, namely, MR-Egger regression, inverse-variance weighted (IVW), weighted median, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods. Result: A causal relationship was identified between the genetically proxied levels of Interleukin (IL) -18, IL-1β, and Regulated upon activation normal T cell expressed and secreted (RANTES) and the risk of MDD (OR = 0.968, 95%CI = 0.938, 0.998, p = 0.036; OR = 0.875, 95%CI = 0.787, 0.971, p = 0.012; OR = 0.947, 95%CI = 0.902, 0.995, p = 0.03; respectively). However, our Mendelian randomization (MR) estimates provided no causality of MDD on inflammatory cytokines. Conclusion: Our study elucidates the connection between inflammatory cytokines and MDD by using MR analysis, thereby enhancing our comprehension of the potential mechanisms. By identifying these associations, our findings hold substantial implications for the development of more effective treatments aimed at improving patient outcomes. However, further investigation is required to fully comprehend the exact biological mechanisms involved.

Dataset Information

Genetically Predicted Circulating Copper and Risk of Chronic Kidney Disease: A Mendelian Randomization Study.

Publications

Genetically Predicted Circulating Copper and Risk of Chronic Kidney Disease: A Mendelian Randomization Study.

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