Educational attainment, body mass index, and smoking as mediators in kidney disease risk: a two-step Mendelian randomization study

Educational attainment (EA) has been linked to various health outcomes, including kidney disease (KD). However, the underlying mechanisms remain unclear. This study aims to assess the causal relationship between EA and KD and quantify the mediation effects of modifiable risk factors using a Mendelian randomization (MR) approach. We performed a two-sample MR analysis utilizing summary statistics from large-scale European genome-wide association studies (GWAS). EA (NGWAS = 766,345) was used as the exposure, and KD (Ncase/Ncontrol= 5,951/212,871) was the outcome. A two-step MR method was applied to identify and quantify the mediation effects of 24 candidate risk factors. Each additional 4.2 years of genetically predicted EA was associated with a 32% reduced risk of KD (odds ratio [OR] 0.68; 95% confidence interval [CI] 0.56, 0.83). Among the 24 candidate risk factors, body mass index (BMI) mediated 21.8% of this protective effect, while smoking heaviness mediated 18.7%. This study provides robust evidence that EA exerts a protective effect against KD, partially mediated by BMI and smoking. These findings highlight the potential for targeted public health interventions aimed at mitigating obesity and smoking-related risks to reduce KD incidence, particularly among individuals with lower educational attainment.

教育程度（Educational attainment，EA）与包括肾脏疾病（Kidney Disease，KD）在内的多种健康结局存在关联，但其潜在作用机制尚不清楚。本研究旨在评估EA与KD之间的因果关系，并采用孟德尔随机化（Mendelian Randomization，MR）方法量化可改变风险因素的中介效应。我们利用欧洲大规模全基因组关联研究（Genome-Wide Association Studies，GWAS）的汇总统计数据开展了两样本孟德尔随机化分析。以EA（样本量NGWAS=766345）作为暴露因素，KD（病例数/对照数=5951/212871）作为结局指标。我们采用两步MR法识别并量化了24种候选风险因素的中介效应。遗传预测的EA每增加4.2年，KD的发病风险可降低32%（比值比[Odds Ratio，OR]=0.68；95%置信区间[Confidence Interval，CI]为0.56~0.83）。在24种候选风险因素中，身体质量指数（Body Mass Index，BMI）介导了21.8%的保护效应，而吸烟量则介导了18.7%的保护效应。本研究提供了可靠证据，表明EA对KD具有保护作用，该作用部分由BMI和吸烟所介导。上述研究结果凸显了针对肥胖及吸烟相关风险开展靶向公共卫生干预的潜力，以降低KD的发病率，尤其是在教育程度较低的人群中。