Causal association between insomnia and diabetic nephropathy independent of diabetes: Evidence from 2-sample Mendelian randomization analysis

This study investigates the putative causal relationship between insomnia and urinary system diseases utilizing Mendelian randomization (MR) analysis. Instrumental variables were systematically selected based on predefined criteria. Two-sample MR analysis was performed employing the inverse variance weighted method as the primary analytical approach. The causal associations between insomnia and common urological diseases were ascertained through odds ratios and their corresponding P values. Methodological validity was assessed using MR-Egger regression for pleiotropy evaluation, Cochran's Q test for heterogeneity assessment, and leave-one-out analysis for sensitivity determination. Positive MR findings underwent validation across multiple datasets, accompanied by preliminary investigation of underlying mechanisms. Within the spectrum of urinary system diseases examined, insomnia exhibited a significant causal association exclusively with diabetic nephropathy. The directional causality demonstrated consistency across various methodological approaches and datasets. Analysis of different insomnia datasets yielded 28 and 39 SNPs as instrumental variables, both successfully satisfying horizontal pleiotropy and heterogeneity criteria. Subsequent MR analyses revealed no evidence of a causal relationship between insomnia and diabetes. Two-sample MR analysis demonstrates a significant causal association between insomnia and diabetic nephropathy, while revealing no direct causal relationships with other common urinary system diseases. This causal association appears to operate independently of insomnia's effects on diabetes.