The causal relationship between COVID-19 and estimated glomerular filtration rate: a bidirectional Mendelian randomization study
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Published on: May 10, 2013
Qiuling Li1, Mengjiao Lin2, Yinghui Deng3
1Department of Nephrology, Blood Purification Center, Zhongshan City People's Hospital, Zhongshan, 528403, China.
Insights
Genetically reduced kidney function, measured by estimated glomerular filtration rate (eGFR), increases the risk of severe COVID-19. However, COVID-19 infection did not appear to impact kidney function in this genetic study.
Area of Science:
- Genetics
- Nephrology
- Infectious Diseases
Background:
- Previous Mendelian studies suggest a link between estimated glomerular filtration rate (eGFR) and severe COVID-19.
- Limited single nucleotide polymorphisms (SNPs) and lack of cystatin C data hindered prior research.
- Genetic mechanisms underlying the eGFR-COVID-19 association require further investigation.
Purpose of the Study:
- To investigate the genetic underpinnings of the association between kidney function (eGFR) and COVID-19 severity in a European population.
- To utilize Mendelian randomization (MR) to assess the causal relationship between eGFR and COVID-19 outcomes.
- To incorporate both creatinine and cystatin C based eGFR estimations.
Main Methods:
- Bidirectional Mendelian randomization (MR) analysis.
- Utilized large-scale genome-wide association study (GWAS) data from CKDGen and UK Biobank (N=1,004,040) for eGFR.
- Analyzed COVID-19 phenotypes (122,616 cases, 2,475,240 controls) from COVID19-hg GWAS meta-analyses.
- Employed the inverse-variance weighted (IVW) method for primary estimation.
Main Results:
- Genetically instrumented reduced eGFR (creatinine-based) significantly increased risk for severe COVID-19 (OR: 2.73), hospitalization (OR: 2.36), and infection (OR: 1.24).
- These associations persisted when using cystatin C-based eGFR.
- No significant causal effect of COVID-19 on eGFR (creatinine or cystatin C based) was detected.
Conclusions:
- A genetic predisposition to reduced kidney function is a potential risk factor for developing severe COVID-19.
- The study did not find evidence for a significant causal effect of COVID-19 on kidney function.
- Further research is warranted to fully elucidate the complex interplay between kidney health and COVID-19.
Background:
Previous Mendelian studies identified a causal relationship between renal function, as assessed by estimated glomerular filtration rate (eGFR), and severe infection with coronavirus disease 2019 (COVID-19). However, much is still unknown because of the limited number of associated single nucleotide polymorphisms (SNPs) of COVID-19 and the lack of cystatin C testing. Therefore, in the present study, we aimed to determine the genetic mechanisms responsible for the association between eGFR and COVID-19 in a European population.
Methods:
We performed bidirectional Mendelian randomization (MR) analysis on large-scale genome-wide association study (GWAS) data; log-eGFR was calculated from the serum levels of creatinine or cystatin C by applying the Chronic Kidney Disease Genetics (CKDGen) Meta-analysis Dataset combined with the UK Biobank (N = 1,004,040) and on COVID-19 phenotypes (122,616 COVID-19 cases and 2,475,240 controls) from COVID19-hg GWAS meta-analyses round 7. The inverse-variance weighted method was used as the main method for estimation.
Results:
Analyses showed that the genetically instrumented reduced log-eGFR, as calculated from the serum levels of creatinine, was associated with a significantly higher risk of severe COVID-19 (odds ratio [OR]: 2.73, 95% confidence interval [CI]: 1.38-5.41, P < 0.05) and significantly related to COVID-19 hospitalization (OR: 2.36, 95% CI: 1.39-4.00, P < 0.05) or infection (OR: 1.24, 95% CI: 1.01-1.53, P < 0.05). The significance of these associations remained when using log-eGFR based on the serum levels of cystatin C as genetically instrumented. However, genetically instrumented COVID-19, regardless of phenotype, was not related to log-eGFR, as calculated by either the serum levels of creatinine or cystatin C.
Conclusions:
Our findings suggest that genetical predisposition to reduced kidney function may represent a risk factor for COVID-19. However, a consistent and significant effect of COVID-19 on kidney function was not identified in this study.
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