Dataset Information

Protein Nutritional Status and Frailty: A Mendelian Randomization Study.

ABSTRACT:

Background

Observational studies have suggested that better protein nutritional status may contribute to prevention of frailty.

Objective

We sought to examine this hypothesis using a Mendelian randomization (MR) analysis.

Methods

We conducted a two-sample MR study using GWAS summary statistics data of the UK Biobank. We applied genetically predicted serum albumin as a primary exposure measure and serum total protein as a secondary exposure measure. The outcome measure was the Rockwood frailty index (FI) based on 49 deficits from 356,432 individuals (53.3% of them were women, with a mean ± SD age of 56.7 ± 8.0 y. The association between serum protein measures and FI was mainly analyzed by use of the inverse variance weighted method.

Results

A genetically predicted serum albumin concentration was not statistically significantly associated with FI in the full sample. However, in women, we observed a preventive association between genetically predicted serum albumin and FI (β = -0.172 per g/L; 95% CI: -0.336, -0.007; P = 0.041). In the full sample, genetically predicted serum total protein was inversely associated with FI (β: -0.153 per g/L; 95% CI: -0.251, -0.056; P = 0.002). In both women and men, higher serum total protein was significantly inversely associated with FI; regression coefficients were -0.148 per g/L (95% CI: -0.287, -0.009; P = 0.037) for women, -0.154 per g/L (95% CI: -0.290, -0.018; P = 0.027) for men.

Conclusions

The present MR study implies that better protein nutritional status modestly contributes to reducing the risk of frailty.

SUBMITTER: Tomata Y

PROVIDER: S-EPMC8754580 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundFrailty 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.MethodsThe 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.ResultsWe 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.ConclusionsFrailty might have no effect on the risk of colon cancer.