Causal associations between environmental factors and risk of IgA nephropathy and membranous nephropathy: a bidirectional Mendelian randomization and mediation analysis

作者：Chunmin Li, Qian Wen, Yanxia Zhang, Jun Wu · 发表于：Renal Failure · 年份：2025 · DOI：10.1080/0886022x.2025.2486620 · 被引用次数：4 · 研究领域：Renal Diseases and Glomerulopathies、Genetic Associations and Epidemiology、Chronic Kidney Disease and Diabetes

Aims IgA nephropathy (IgAN) and membranous nephropathy (MN) have intricate etiologies that are poorly understood. This study aimed to investigate the impact of genetically predicted environmental factors on IgAN and MN.Methods We used bidirectional two-step Mendelian randomization (MR) analysis utilizing large-scale genome-wide association study (GWAS) data to investigate the relationships between 68 environmental exposures and IgAN and MN. The main method is inverse variance weighted (IVW). Sensitivity analyses were conducted to validate the causal estimates. Furthermore, the two-step MR was used to explore possible mediating effects.Results A total of 20 significant causal associations were identified. Genetically predicted educational attainment (EA), average household income, gluten-free diet, cheese intake, fresh fruit intake, cognitive performance, and intelligence were associated with a reduced risk of IgAN (p < 0.05); whereas frequency of alcohol consumption, insomnia, triglycerides, transferrin saturation, percentage body fat, body mass index (BMI), waist circumference, and blood pressure were associated with the risk of IgAN (p < 0.05). Genetically predicted EA and moderate to vigorous physical activity were associated with a reduced risk of MN (p < 0.05); on the other hand, beef intake, waist-to-hip ratio, and nitrogen oxides were associated with the risk of MN (p < 0.05). In addition, we observed that insomnia, BMI, and waist circumference partially mediated the c...