Background: Education might be causal to type 2 diabetes mellitus (T2DM). We triangulated cohort and genetic evidence to consolidate the causality between education and T2DM. Methods: We obtained observational evidence from the English Longitudinal Study of Ageing (ELSA). Self-reporting educational attainment was categorised as high (post-secondary and higher), middle (secondary), and low (below secondary or no academic qualifications) in 6,787 community-dwelling individuals aged ≥50 years without diabetes at ELSA wave 2, who were followed until wave 8 for the first diabetes diagnosis. Additionally, we performed two-sample Mendelian randomisation (MR) using an inverse-variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode-based estimate (WMBE) method. Steiger filtering was further applied to exclude single-nucleotide polymorphisms (SNPs) that were correlated with an outcome (T2DM) stronger than exposure (education attainment). Results: We observed 598 new diabetes cases after 10.4 years of follow-up. The adjusted hazard ratios (95%CI) of T2DM were 1.20 (0.97-1.49) and 1.58 (1.28-1.96) in the middle- and low-education groups, respectively, compared to the high-education group. Low education was also associated with increased glycated haemoglobin levels. Psychosocial resources, occupation, and health behaviours fully explained these inverse associations. In the MR analysis of 210 SNPs (R2=0.0161), the odds ratio of having T2DM per standard deviation-decreasing years (4.2 years) of schooling was 1.33 (1.01-1.75; IVW), 1.23 (0.37-4.17; MR-Egger), 1.56 (1.09-2.27; WM), and 2.94 (0.98-9.09; WMBE). However, applying Steiger filtering attenuated most MR results toward the null. Conclusions: Our inconsistent findings between cohort and genetic evidence did not support the causality between education and T2DM.

中文翻译：

---

教育水平是 2 型糖尿病的一个原因：观察和遗传证据三角测量的注意事项

背景：教育可能是 2 型糖尿病 (T2DM) 的原因。我们对队列和遗传证据进行三角测量，以巩固教育与 T2DM 之间的因果关系。方法：我们从英国衰老纵向研究 (ELSA) 中获得了观察性证据。在 ELSA 第 2 波中，6,787 名 50 岁以上无糖尿病的社区居民的自我报告教育程度被分为高（大专及以上）、中（大专）和低（中学以下或无学历），他们随访至第 8 波以进行首次糖尿病诊断。此外，我们使用逆方差加权 (IVW)、MR-Egger、加权中位数 (WM) 和基于加权模式的估计 (WMBE) 方法进行了两样本孟德尔随机化 (MR)。进一步应用 Steiger 过滤以排除与结果 (T2DM) 相关的单核苷酸多态性 (SNP) 强于暴露（教育程度）。结果：我们在 10.4 年的随访后观察到 598 例新的糖尿病病例。与高等教育组相比，中低教育组 T2DM 的调整后风险比 (95%CI) 分别为 1.20 (0.97-1.49) 和 1.58 (1.28-1.96)。受教育程度低也与糖化血红蛋白水平升高有关。社会心理资源、职业和健康行为充分解释了这些反向关联。在 210 个 SNP (R2=0.0161) 的 MR 分析中，每个标准差减少年数（4.2 年）的学校教育中患有 T2DM 的优势比为 1.33（1.01-1.75；IVW）、1.23（0.37-4.17；MR-Egger） )、1.56 (1.09-2.27; WM) 和 2.94 (0.98-9.09; WMBE)。然而，应用 Steiger 过滤将大多数 MR 结果衰减到零。结论：我们在队列和遗传证据之间不一致的发现不支持教育和 T2DM 之间的因果关系。