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Blood metabolites mediate the impact of lifestyle factors on the risk of urolithiasis: a multivariate, mediation Mendelian randomization study

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Abstract

Urolithiasis is closely linked to lifestyle factors. However, the causal relationship and underlying mechanisms remain unclear. This study aims to investigate the relationship between lifestyle factors and the onset of urolithiasis and explore potential blood metabolite mediators and their role in mediating this relationship. In this study, we selected single nucleotide polymorphisms (SNPs) as instrumental variables if they exhibited significant associations with our exposures in genome-wide association studies (GWAS) (p < 5.0 × 10-8). Summary data for urolithiasis came from the FinnGen database, including 8597 cases and 333,128 controls. We employed multiple MR analysis methods to assess causal links between genetically predicted lifestyle factors and urolithiasis, as well as the mediating role of blood metabolites. A series of sensitivity and pleiotropy analyses were also conducted. Our results show that cigarettes smoked per day (odds ratio [OR] = 1.159, 95% confidence interval [CI] = 1.004-1.338, p = 0.044) and alcohol intake frequency (OR = 1.286, 95% CI = 1.056-1.565, p = 0.012) were positively associated with increased risk of urolithiasis, while tea intake (OR = 0.473, 95% CI = 0.299-0.784, p = 0.001) was positively associated with reduced risk of urolithiasis. Mediation analysis identifies blood metabolites capable of mediating the causal relationship between cigarettes smoked per day, tea intake and urolithiasis. We have come to the conclusion that blood metabolites serve as potential causal mediators of urolithiasis, underscoring the importance of early lifestyle interventions and metabolite monitoring in the prevention of urolithiasis.

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Data availability

The data used to support the findings of this study are available from the corresponding authors upon reasonable request.

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Acknowledgements

We thank Kettunen et al, FinnGen consortium, the UK Biobank and Nightingale Health Ltd for providing GWAS data.

Funding

This study was supported by the Key Research and Development Program of Hubei province (2023BCB001), the Translational Medicine and Multidisciplinary Research Project of Zhongnan Hospital of Wuhan University (ZNJC202217, ZNJC202232).

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  1. Zhilong Li and Houyi Wei have contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China

    Zhilong Li, Xiaoyu Tang, Tongzu Liu, Sheng Li & Xinghuan Wang

  2. Department of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, China

    Houyi Wei

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Contributions

XW, SL and TL: were responsible for the concept and design. ZL and HW: collected the data and the data analysis. ZL: interpreted the results and wrote the manuscript. XW, SL, TL, HW and XT: assisted in revising the manuscript. All authors have read and approved this manuscript.

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Correspondence to Tongzu Liu, Sheng Li or Xinghuan Wang.

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Li, Z., Wei, H., Tang, X. et al. Blood metabolites mediate the impact of lifestyle factors on the risk of urolithiasis: a multivariate, mediation Mendelian randomization study. Urolithiasis 52, 44 (2024). https://doi.org/10.1007/s00240-024-01545-8

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