Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia.
Orthopaedics, Gold Coast Hospital and Health Service, Southport, Queensland, Australia.
BMJ Open. 2021 Jan 12;11(1):e045210. doi: 10.1136/bmjopen-2020-045210.
Level of education and genetic risk are key predictors of cardiovascular disease (CVD). While several studies have explored the causal mechanisms of education effects, it remains uncertain to what extent genetic risk is mediated by established CVD risk factors. This study sought to investigate this and explored the mediation of education and genetic effects on CVD by established cardiovascular risk factors in the Framingham Heart Study (FHS).
Prospective observational cohort study.
7017 participants from the FHS.
Community-based cohort of adults in Framingham, Massachusetts, USA.
Incident CVD. The total effects of education and genetic predisposition using a 63-variant genetic risk score (GRS) on CVD, as well as those mediated by established CVD risk factors, were assessed via mediation analysis based on the counterfactual framework using Cox proportional hazards regression models.
Over a median follow-up time of 12.0 years, 1091 participants experienced a CVD event. Education and GRS displayed significant associations with CVD after adjustment for age and sex and the established risk factors smoking, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), body mass index, systolic blood pressure (SBP) and diabetes. For education effects, smoking, HDL-C and SBP were estimated to mediate 18.8% (95% CI 9.5% to 43%), 11.5% (95% CI 5.7% to 29.0%) and 4.5% (95% CI 1.6% to 13.3%) of the total effect of graduate degree, respectively, with the collective of all risk factors combined mediating 38.5% (95% 24.1% to 64.9%). A much smaller proportion of the effects of GRS were mediated by established risk factors combined (17.6%, 95% CI 2.4% to 35.7%), with HDL-C and TC mediating 11.5% (95% CI 6.2% to 21.5%) and 3.1% (95% CI 0.2% to 8.3%), respectively.
Unlike education inequalities, established risk factors mediated only a fraction of GRS effects on CVD. Further research is required to elucidate the underlying causal mechanisms of genetic contributions to CVD.
教育程度和遗传风险是心血管疾病（CVD）的关键预测因素。虽然已有多项研究探讨了教育效应的因果机制，但遗传风险在多大程度上受已确立的 CVD 风险因素的影响仍不确定。本研究旨在探讨这一点，并在弗雷明汉心脏研究（FHS）中通过已确立的心血管风险因素研究教育和遗传效应对 CVD 的中介作用。
前瞻性观察队列研究。
来自 FHS 的 7017 名参与者。
美国马萨诸塞州弗雷明汉的社区为基础的成年人队列。
CVD 事件。使用 63 个变异基因风险评分（GRS）评估教育和遗传易感性对 CVD 的总效应，以及通过基于反事实框架的中介分析，利用 Cox 比例风险回归模型评估通过已确立的 CVD 风险因素中介的效应。
在中位数为 12.0 年的随访期间，1091 名参与者发生了 CVD 事件。在调整年龄和性别以及已确立的风险因素吸烟、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、体重指数、收缩压（SBP）和糖尿病后，教育程度和 GRS 与 CVD 呈显著相关。对于教育程度的影响，吸烟、HDL-C 和 SBP 分别估计可介导研究生学位总效应的 18.8%（95%CI 9.5%至 43%）、11.5%（95%CI 5.7%至 29.0%）和 4.5%（95%CI 1.6%至 13.3%），所有风险因素的综合作用可介导 38.5%（95%CI 24.1%至 64.9%）。由已确立的风险因素综合介导的 GRS 效应的比例要小得多（17.6%，95%CI 2.4%至 35.7%），其中 HDL-C 和 TC 分别介导 11.5%（95%CI 6.2%至 21.5%）和 3.1%（95%CI 0.2%至 8.3%）。
与教育不平等不同，已确立的风险因素仅能部分解释 GRS 对 CVD 的影响。需要进一步的研究来阐明遗传因素对 CVD 的潜在因果机制。
