Insights into risk factors for urolithiasis: a mendelian randomization study.

ABSTRACT

BACKGROUND: Risk factors for urolithiasis have not been identified. Here, we aimed to identify potentially causal risk factors driving the risk of urolithiasis. METHODS: Two sets of instrumental variables were used for analysis, derived from publicly available databases. Summary-level statistical data for urolithiasis were obtained from the MRC-IEU Consortium and UK biobank (Neale Lab). Mendelian randomization (MR) was conducted to identify causal risk of urolithiasis. Finally, the results of the two databases were combined and a meta-analysis was performed. RESULTS: In the MRC-IEU consortium, the odds of urolithiasis increased per 1-SD increase of body mass index (BMI) (OR = 1.0016, 95% CI1.0004-1.0029, p = 0.010), triglycerides (OR = 1.0016, 95% CI1.0003-1.0029, p = 0.017), adiponectin (OR = 1.0027, 95% CI1.0003-1.0050, p = 0.024), and body fat percentage (OR = 1.008, 95% CI1.0001-1.0161, p = 0.047). In addition, alcohol intake also increased the incidence of urolithiasis (OR = 1.0030, 95% CI1.0009-1.0051, p = 0.005). In the UK biobank, the odds of urolithiasis increased per 1-SD increase of waist circumference (OR = 1.0215, 95% CI1.0061-1.0372, p = 0.008) and body fat percentage (OR = 1.0239, 95% CI1.0043-1.0440, p = 0.020). Surprisingly, we found that the risk of urolithiasis decreased with increasing hip circumference (OR = 0.9954, 95% CI0.9915-0.9992, p = 0.017). In a meta-analysis of MR results, higher BMI (OR = 1.0016, 95% CI1.0004-1.0027, p = 0.009), waist circumference (OR = 1.0073, 95% CI1.0020-1.0126, p = 0.007), adiponectin (OR = 1.0026, 95% CI1.0008-1.0043, p = 0.004), triglycerides (OR = 1.0015, 95% CI1.0004-1.0026, p = 0.008) and body fat percentage (OR = 1.0104, 95% CI1.0030-1.0178, p = 0.006) increased the risk of urolithiasis. Furthermore, alcohol intake also increased the incidence of urolithiasis (OR = 1.0033, 95% CI1.0012-1.0053, p = 0.002). CONCLUSIONS: Our MR study found that higher BMI, triglycerides, waist circumference, adiponectin, body fat percentage, and alcohol intake increased the risk of urolithiasis.