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

• Published in: Urolithiasis 2024-03, Vol.52 (1), p.44, Article 44
• Main Authors: Li, Zhilong, Wei, Houyi, Tang, Xiaoyu, Liu, Tongzu, Li, Sheng, Wang, Xinghuan
• Format: Article
• Language: English
• Subjects: Genome-Wide Association Study; Humans; Life Style; Lifestyles; Medical Biochemistry; Medicine; Medicine & Public Health; Mendelian Randomization Analysis; Metabolites; Nephrology; Tea; Urinary tract diseases; Urolithiasis - etiology; Urolithiasis - genetics; Urology
• ISSN: 2194-7236; 2194-7228; 2194-7236
• DOI: 10.1007/s00240-024-01545-8

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.