The Frailty Index and colon cancer: a 2-sample Mendelian-randomization study

Abstract

Background Frailty is closely related to cancer. Previous research has shown that cancer patients are prone to frailty, and frailty increases the risk of adverse outcomes in cancer patients. However, it is unclear whether frailty increases the risk of cancer. This 2-sample Mendelian-randomization (MR) study sought to analyze the relationship between frailty and the risk of colon cancer. Methods The database was extracted from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) in 2021. The genome-wide association study (GWAS) data related to colon cancer was obtained from the GWAS website ( http://gwas.mrcieu.ac.uk/datasets ), involving 462,933 individuals’ gene information. Single-nucleotide polymorphisms (SNPs) were defined as the instrumental variables (IVs). The SNPs closely associated with the Frailty Index at a genome-wide significance level were selected. To further screen the IVs, we selected the confounding factors using the PhenoScanner ( http://www.phenoscanner.medschl.cam.ac.uk/phenoscanner ). To estimate the causal effect of the Frailty Index on colon cancer, the MR-Egger regression, weighted median (WM1), inverse-variance weighted (IVW), and weight mode (WM2) methods were applied to calculate the SNP-frailty index and the SNP-cancer estimates. Cochran’s Q statistic was used to estimate heterogeneity. The two-sample Mendelian randomization (TSMR) analysis was performed using the “TwoSampleMR” and “plyr” packages. All the statistical tests were 2-tailed, and a P value <0.05 was considered statistically significant. Results We selected 8 SNPs as the IVs. The results of the IVW analysis [odds ratio (OR) =0.995, 95% confidence interval (CI): 0.990–1.001, P=0.052] showed that the genetic changes in the Frailty Index were not statistically associated with the risk of colon cancer, and no significant heterogeneity between these 8 genes was observed (Q =7.382, P=0.184). The MR-Egger (OR =0.987, 95% CI: 0.945–1.031, P=0.581), WM1 (OR =0.995, 95% CI: 0.990–1.001, P=0.118), WM2 (OR =0.996, 95% CI: 0.988–1.004, P=0.356), and SM (OR =0.996, 95% CI: 0.987–1.005, P=0.449) results were also consistent with each other. The sensitivity analysis based on the leave-one-out method showed that the individual SNPs did not affect the robustness of the results. Conclusions Frailty might have no effect on the risk of colon cancer.

Stroke and frailty index: a two-sample Mendelian randomisation study

“…To meet the above hypotheses, the specific instrumental variables screening criteria were: (1) the association of single nucleotide polymorphism(SNPs) with single amino acids was genome-wide significant (P < 5 × 10 −8 ); (2) the linkage disequilibrium (LD) between SNPs was calculated using the European population genome of 1000 individuals as the reference template, and SNPs with r 2 < 0.001 and physical genetic distance > 10,000 kb were screened. (3) remove SNPs with minor allele frequencies < 0.01;(4) exclude SNPs with F values < 10 to avoid weak instrumental bias,and the following formula was used to calculate the F statistic [ 17 ]: F statistic = R 2 (N–2)/(1–R 2 ). R 2 = 2 × EAF × (1–EAF) × β 2 .The F values were all > 10, which indicated that our IVs were not biased by weak instrument.…”

Investigation of the causal relationship between inflammatory bowel disease and type 2 diabetes mellitus: a Mendelian randomization study

“…It has been verified that the Weighted Median approach outperforms the MR-Egger regression regarding lowering the type I error and higher causal estimate power (Ding et al, 2023). Finally, a leaveone-out (LOO) analysis was undertaken to determine whether any particular SNP is disproportionately responsible for the outcome of any MR study (Gao et al, 2023). Applying Bonferroni correction for multiple testing, a p-value below 2.1E−03 was considered as signifcant.…”

Bidirectional causal relational between frailty and mental illness: a two-sample Mendelian randomization study

“…It utilizes genetic variation as an instrumental variable (IV) to evaluate the consistency of observational associations between risk factors and outcomes with causal effects, making it a valuable approach that provide a high level of evidence ( 12 ). Recently, the MR approaches have been successfully applied to reveal the causal role of frailty in various health outcomes ( 13 – 15 ). At present, there is limited research exploring the association between frailty and MI, and the existence of a causal relationship between the two remains uncertain.…”