tetano
Editor, Senior Moderator
BMC Nephrol
. 2024 Jan 15;25(1):21.
doi: 10.1186/s12882-023-03443-4. The causal relationship between COVID-19 and estimated glomerular filtration rate: a bidirectional Mendelian randomization study
Qiuling Li[SUP] 1 [/SUP], Mengjiao Lin[SUP] 2 [/SUP], Yinghui Deng[SUP] 3 [/SUP], Haozhang Huang[SUP] 4 5 6 [/SUP]
Affiliations
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.
Keywords: Coronavirus Disease 2019; Estimated glomerular filtration rate; Kidney function; Mendelian randomization; Single nucleotide polymorphism.
. 2024 Jan 15;25(1):21.
doi: 10.1186/s12882-023-03443-4. The causal relationship between COVID-19 and estimated glomerular filtration rate: a bidirectional Mendelian randomization study
Qiuling Li[SUP] 1 [/SUP], Mengjiao Lin[SUP] 2 [/SUP], Yinghui Deng[SUP] 3 [/SUP], Haozhang Huang[SUP] 4 5 6 [/SUP]
Affiliations
- PMID: 38225574
- DOI: 10.1186/s12882-023-03443-4
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.
Keywords: Coronavirus Disease 2019; Estimated glomerular filtration rate; Kidney function; Mendelian randomization; Single nucleotide polymorphism.