Advancing age is one of the strongest risk factors for osteoarthritis (OA). DNA methylation-based measures of epigenetic age acceleration may provide insights into mechanisms underlying OA. We analyzed data from the Multicenter Osteoarthritis Study in a subset of 671 participants ages 45–69 years with no or mild radiographic knee OA. DNA methylation was assessed with the Illumina Infinium MethylationEPIC 850K array. We calculated predicted epigenetic age according to Hannum, Horvath, PhenoAge, and GrimAge epigenetic clocks, then regressed epigenetic age on chronological age to obtain the residuals. Associations between the residuals and knee, hand, and multi-joint OA were assessed using logistic regression, adjusted for chronological age, sex, clinical site, smoking status, and race. Twenty-three percent met criteria for radiographic hand OA, 25% met criteria for radiographic knee OA, and 8% met criteria for multi-joint OA. Mean chronological age (SD) was 58.4 (6.7) years. Mean predicted epigenetic age (SD) according to Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks was 64.9 (6.4), 68.6 (5.9), 50.5 (7.7), and 67.0 (6.2), respectively. Horvath epigenetic age acceleration was not associated with an increased odds of hand OA, odds ratio (95% confidence intervals) = 1.03 (0.99–1.08), with similar findings for knee and multi-joint OA. We found similar magnitudes of associations for Hannum epigenetic age, PhenoAge, and GrimAge acceleration compared to Horvath epigenetic age acceleration. Epigenetic age acceleration as measured by various well-validated epigenetic clocks based on DNA methylation was not associated with increased risk of knee, hand, or multi-joint OA independent of chronological age.

中文翻译：

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在多中心骨关节炎研究 (MOST) 中评估表观遗传年龄加速与骨关节炎的关联

年龄增长是骨关节炎 (OA) 的最强危险因素之一。基于 DNA 甲基化的表观遗传年龄加速测量可能有助于深入了解 OA 的潜在机制。我们分析了多中心骨关节炎研究的数据，其中包括 671 名年龄 45-69 岁、没有或轻度膝关节骨关节炎的受试者。使用 Illumina Infinium MmethylationEPIC 850K 阵列评估 DNA 甲基化。我们根据 Hannum、Horvath、PhenoAge 和 GrimAge 表观遗传时钟计算了预测的表观遗传年龄，然后根据实际年龄回归表观遗传年龄以获得残差。使用逻辑回归评估残差与膝、手和多关节 OA 之间的关联，并根据实际年龄、性别、临床部位、吸烟状况和种族进行调整。 23% 的人符合放射学手部 OA 的标准，25% 符合放射学膝部 OA 的标准，8% 符合多关节 OA 的标准。平均实足年龄 (SD) 为 58.4 (6.7) 岁。根据 Horvath、Hannum、PhenoAge 和 GrimAge 表观遗传时钟的平均预测表观遗传年龄 (SD) 分别为 64.9 (6.4)、68.6 (5.9)、50.5 (7.7) 和 67.0 (6.2)。 Horvath 表观遗传年龄加速与手部 OA 的几率增加无关，比值比（95% 置信区间）= 1.03 (0.99–1.08)，膝关节和多关节 OA 的发现类似。我们发现与 Horvath 表观遗传年龄加速相比，Hannum 表观遗传年龄、PhenoAge 和 GrimAge 加速的关联程度相似。通过基于 DNA 甲基化的各种经过充分验证的表观遗传时钟测量的表观遗传年龄加速与膝盖、手或多关节 OA 风险增加无关，与实际年龄无关。