Insights into risk factors for urolithiasis: a mendelian randomization study

Risk factors for urolithiasis have not been identified. Here, we aimed to identify potentially causal risk factors driving the risk of urolithiasis. 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. In the MRC-IEU consortium, the odds of urolithiasis increased per 1-SD increase of body mass index (BMI) (OR = 1.0016, 95% CI:1.0004-1.0029, p = 0.010), triglycerides (OR = 1.0016, 95% CI:1.0003-1.0029, p = 0.017), adiponectin (OR = 1.0027, 95% CI:1.0003-1.0050, p = 0.024), and body fat percentage (OR = 1.008, 95% CI:1.0001-1.0161, p = 0.047). In addition, alcohol intake also increased the incidence of urolithiasis (OR = 1.0030, 95% CI:1.0009-1.0051, p = 0.005). In the UK biobank, the odds of urolithiasis increased per 1-SD increase of waist circumference (OR = 1.0215, 95% CI:1.0061-1.0372, p = 0.008) and body fat percentage (OR = 1.0239, 95% CI:1.0043-1.0440, p = 0.020). Surprisingly, we found that the risk of urolithiasis decreased with increasing hip circumference (OR = 0.9954, 95% CI:0.9915-0.9992, p = 0.017). In a meta-analysis of MR results, higher BMI (OR = 1.0016, 95% CI:1.0004-1.0027, p = 0.009), waist circumference (OR = 1.0073, 95% CI:1.0020-1.0126, p = 0.007), adiponectin (OR = 1.0026, 95% CI:1.0008-1.0043, p = 0.004), triglycerides (OR = 1.0015, 95% CI:1.0004-1.0026, p = 0.008) and body fat percentage (OR = 1.0104, 95% CI:1.0030-1.0178, p = 0.006) increased the risk of urolithiasis. Furthermore, alcohol intake also increased the incidence of urolithiasis (OR = 1.0033, 95% CI:1.0012-1.0053, p = 0.002). Our MR study found that higher BMI, triglycerides, waist circumference, adiponectin, body fat percentage, and alcohol intake increased the risk of urolithiasis.