Genetically predicted frailty index and risk of chronic kidney disease

Sep 19, 2024Scientific reports

Genetic links between frailty and risk of chronic kidney disease

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

A total of 14 genetic markers were identified as effective tools to analyze the connection between frailty and chronic kidney disease.

The analysis indicated a causal association between and chronic kidney disease, supported by multiple statistical methods.
The inverse-variance weighted method showed a beta value of 1.270, suggesting a significant relationship.
-Egger analysis also indicated a causal link, with a beta value of 3.612.
Directional pleiotropy was unlikely to affect the results, as indicated by the MR-Egger regression.
Multivariable Mendelian randomization analysis confirmed the association even after adjusting for various potential confounding factors.

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Previous findings have reported the association between frailty and chronic kidney disease. However, the causality remains ambiguous. This study aimed to determine whether is causally associated with chronic kidney disease. We obtained the frailty genome-wide association study (GWAS) data and chronic kidney disease GWAS data from the FinnGen R5 (total n = 216,743; case = 3902, control = 212,841) as the exposure and outcome, respectively. A two-sample (MR) analysis was primarily conducted using the inverse-variance weighted (IVW), weighted median and MR-Egger regression analyses. Multivariable MR analysis (MVMR) was conducted for additional adjustment. In the two-sample Mendelian randomization analyses, a total of 14 single nucleotide polymorphisms (SNPs) were recognized as effective instrumental variables. The IVW method showed evidence to support a causal association between frailty index and chronic kidney disease (beta = 1.270; 95% CI 0.608 to 1.931; P < 0.001). MR-Egger revealed a causal association between frailty index and chronic kidney disease (beta = 3.612; 95% CI 0.805 to 6.419; P = 0.027). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = - 0.053; P = 0.119). The weighted median approach and weighted mode method also demonstrated a causal association between frailty index and chronic kidney disease (beta = 1.148; 95% CI 0.278 to 2.019; P = 0.011; beta = 2.194; 95% CI 0.598 to 3.790; P = 0.018). Cochran's Q test and the funnel plot indicated no directional pleiotropy. MVMR analysis revealed that the causal association between frailty index and chronic kidney disease remained after adjusting for potential confounders, body-mass index, inflammatory bowel disease, waist-hip ratio, and C-reactive protein. Our study provides evidence of causal association between frailty and chronic kidney disease from genetic perspectives.

Key numbers

1.270

Increase in CKD risk

Beta coefficient from the IVW method

Number of SNPs analyzed

Total SNPs associated with

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Genetically predicted frailty index and risk of chronic kidney disease

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