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Genetic predisposition to white blood cells in relation to the risk of frailty

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Abstract

Background

Observational studies have suggested an association between white blood cells (WBCs) and frailty, but considering the susceptibility to reverse causality and confounding, the causal direction and magnitude of this association remain ambiguous. Our aim was to investigate the causal effect of WBCs on frailty by means of a Mendelian randomization (MR) analysis.

Methods

Based on the genome-wide association study (GWAS) summary statistics data provided by the European Bioinformatics Institute (EBI), we carried out a two-sample MR study. We applied the genetically predicted independent WBCs from GWAS as a measure of exposure data. The Rockwood Frailty Index (FI) was used as outcome measure, which was derived from a meta-analysis from GWAS in UK Biobank European ancestry participants and Swedish TwinGene participants. Our study applied inverse variance weighted (IVW), weighted median, Mendelian randomization-Egger (MR-Egger) and outlier test (MR-PRESSO) methods to explore relationships between various WBCs and frailty.

Results

In our study, a possible causal relationship between eosinophil levels and frailty was demonstrated by two-sample MR analysis. Eosinophils were associated with FI (beta:0.0609; 95% CI 0.0382, 0.0836; P = 1.38E–07). Our results suggest that as the level of eosinophils increases, so does the risk of frailty. No meaningful causal relationship between neutrophils, lymphocytes, monocytes or basophils and FI was found in the MR results (P > 0.05).

Conclusions

According to this MR study, higher eosinophil counts are related to an increased risk of frailty. To validate these findings and investigate the mechanisms underlying these connections, future studies are warranted.

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Data availability

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

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Acknowledgements

Our data, analytic methods or materials are available to other researchers. We used summary statistics from a genome-wide association study (GWAS) and then performed two-sample MR analyses. Details are in the section of the original article. Since the data can be available to everyone, the studies reported in the manuscript were not pre-registered.This study was funded by the National Key R&D Program of China (2020YFC2008900), the National Natural Science Foundation of China (81701366), Zhejiang Public Welfare Technology Application Program Project (LGF22H250001), the Medical Health Science and Technology Project of Zhejiang Province(2022RC149).

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Authors and Affiliations

  1. Department of Geriatics, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China

    Li Wu, Xiao-hong Zhao, Shi-xian Zhou & Jing-jin Jiang

  2. Key Laboratory of Diagnosis and Treatment of Aging and Physic-Chemical Injury Diseases of Zhejiang Province, Hangzhou, 310003, China

    Li Wu, Xiao-hong Zhao, Shi-xian Zhou & Jing-jin Jiang

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Correspondence to Jing-jin Jiang.

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Wu, L., Zhao, Xh., Zhou, Sx. et al. Genetic predisposition to white blood cells in relation to the risk of frailty. Aging Clin Exp Res 35, 3023–3031 (2023). https://doi.org/10.1007/s40520-023-02609-2

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