Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Institute for Infection and Immunity, St George's University of London, London, United Kingdom; St George's University Hospitals NHS Foundation Trust, London, United Kingdom.
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
Osteoarthritis Cartilage. 2021 Mar;29(3):365-371. doi: 10.1016/j.joca.2020.12.015. Epub 2021 Jan 7.
To investigate which cardiometabolic factors underlie clustering of osteoarthritis (OA) with cardiovascular disease, and the extent to which these mediate an effect of education.
Genome-wide association study (GWAS) of OA was performed in UK Biobank (60,800 cases and 328,251 controls) to obtain genetic association estimates for OA risk. Genetic instruments and association estimates for body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), smoking and education were obtained from existing GWAS summary data (sample sizes 188,577-866,834 individuals). Two-sample Mendelian randomization (MR) analyses were performed to investigate the effects of exposure traits on OA risk. MR mediation analyses were undertaken to investigate whether the cardiometabolic traits mediate any effect of education on OA risk.
MR analyses identified protective effects of higher genetically predicted education (main MR analysis odds ratio (OR) per standard deviation increase 0.59, 95% confidence interval (CI) 0.54-0.64) and LDL-C levels (OR 0.94, 95%CI 0.91-0.98) on OA risk, and unfavourable effects of higher genetically predicted BMI (OR 1.82, 95%CI 1.73-1.92) and smoking (OR 2.23, 95%CI 1.85-2.68). There was no strong evidence of an effect of genetically predicted SBP on OA risk (OR 0.98, 95% CI 0.90-1.06). The proportion of the effect of genetically predicted education mediated through genetically predicted BMI and smoking was 35% (95%CI 13-57%).
These findings highlight education, obesity and smoking as common mechanisms underlying OA and cardiovascular disease. These risk factors represent clinical and public health targets for reducing multi-morbidity related to the burden these common conditions.
探究心血管疾病合并骨关节炎（OA）的代谢因素，并探讨这些因素在多大程度上可以介导教育的影响。
在英国生物银行（60800 例病例和 328251 例对照）中进行全基因组关联研究（GWAS），以获得 OA 风险的遗传关联估计值。体重指数（BMI）、低密度脂蛋白胆固醇（LDL-C）、收缩压（SBP）、吸烟和教育的遗传工具和关联估计值从现有的 GWAS 汇总数据（样本量 188577-866834 人）中获得。进行两样本孟德尔随机化（MR）分析，以研究暴露特征对 OA 风险的影响。进行 MR 中介分析，以研究代谢特征是否可以介导教育对 OA 风险的影响。
MR 分析确定了较高遗传预测教育（主要 MR 分析优势比（OR）每标准偏差增加 0.59，95%置信区间（CI）0.54-0.64）和 LDL-C 水平（OR 0.94，95%CI 0.91-0.98）对 OA 风险的保护作用，以及较高遗传预测 BMI（OR 1.82，95%CI 1.73-1.92）和吸烟（OR 2.23，95%CI 1.85-2.68）的不利影响。没有强有力的证据表明遗传预测 SBP 对 OA 风险有影响（OR 0.98，95%CI 0.90-1.06）。遗传预测教育通过遗传预测 BMI 和吸烟对 OA 风险的影响比例为 35%（95%CI 13-57%）。
这些发现强调了教育、肥胖和吸烟是 OA 和心血管疾病的共同机制。这些危险因素代表了临床和公共卫生的目标，可减少与这些常见疾病相关的多发病。
