Our MR study shows causal associations of earlier smoking initiation, increased sedentary behavior, urinary sodium, the urinary sodium/potassium ratio, the urinary sodium/creatinine ratio, serum calcium, 25OHD, eGFRcrea, eGFRcys, BMI, waist circumference, fasting insulin, glycated hemoglobin, a history of T2DM, and hypertension with an increased risk of kidney stones. The gene discussed is INS; the disease is nephrolithiasis.