Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Department of Nursing, College of Nursing, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
J Gerontol A Biol Sci Med Sci. 2024 Jan 1;79(1). doi: 10.1093/gerona/glad213.
This is the first known comparative assessment of the associations of epigenetic age estimates with the prevalence of rheumatoid arthritis (RA). We used data available in Gene Expression Omnibus (GSE42861) from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study. Information regarding RA diagnosis and 450K DNA methylation (DNAm) of 18- to 70-year-old participants was available. Utilizing Horvath's online DNAm Age Calculator, we determined the DNAm estimate of Telomere length (DNAmTL), Hannum's epigenetic age, Horvath's 2013 and 2018 epigenetic ages, PhenoAge, GrimAge, and the respective age-acceleration measures. The association of RA prevalence with epigenetic age measures was assessed using linear regression, adjusting for sex and smoking status. The p values were corrected for multiple testing using a false discovery rate. We identified statistically significant associations of RA with Horvath 2013 age acceleration (estimate: -1.34; FDR p value: 1.0 × 10-2), Horvath 2018 age acceleration (estimate: -1.32; FDR p value: 4.0 × 10-5), extrinsic age acceleration (estimate: 1.34; FDR p value: 1.0 × 10-2), PhenoAge acceleration (estimate: 2.31; FDR p value: 1.1 × 10-5), GrimAge (estimate: 2.54; FDR p value: 1.0 × 10-2), and GrimAge acceleration (estimate: 3.15; FDR p-value: 1.7 × 10-17). Of note, the raw and age-adjusted GrimAge surrogate DNAm protein components were significantly higher in RA cases than controls. Interestingly, the first-generation measures were associated only with women. No sex-specific effects were identified for PhenoAge or GrimAge accelerations. In this cross-sectional assessment, the second-generation clocks show promise as markers of biological aging, with higher epigenetic age acceleration observed in RA cases compared with healthy controls.
这是首次对表观遗传年龄估计与类风湿关节炎 (RA) 患病率的相关性进行的比较评估。我们使用了瑞典类风湿关节炎流行病学研究中可从基因表达综合数据库 (GSE42861) 获得的数据。研究中提供了关于 RA 诊断和 18 至 70 岁参与者的 450K 甲基化 DNA（DNAm）的信息。我们利用 Horvath 的在线 DNAm 端粒长度（DNAmTL）年龄计算器、Hannum 的表观遗传年龄、Horvath 的 2013 年和 2018 年表观遗传年龄、PhenoAge、GrimAge 以及各自的年龄加速指标，来确定 DNAm 估计值。我们使用线性回归评估了 RA 患病率与表观遗传年龄指标的相关性，调整了性别和吸烟状况。使用错误发现率对 p 值进行了多重检验校正。我们发现 RA 与 Horvath 2013 年年龄加速（估计值：-1.34；FDR p 值：1.0×10-2）、Horvath 2018 年年龄加速（估计值：-1.32；FDR p 值：4.0×10-5）、外在年龄加速（估计值：1.34；FDR p 值：1.0×10-2）、PhenoAge 加速（估计值：2.31；FDR p 值：1.1×10-5）、GrimAge（估计值：2.54；FDR p 值：1.0×10-2）和 GrimAge 加速（估计值：3.15；FDR p 值：1.7×10-17）之间存在统计学显著关联。值得注意的是，RA 病例的原始和年龄调整后的 GrimAge 替代 DNAm 蛋白质成分明显高于对照组。有趣的是，第一代指标仅与女性相关。未发现 PhenoAge 或 GrimAge 加速存在性别特异性影响。在这项横断面评估中，第二代时钟有望成为生物衰老的标志物，与健康对照组相比，RA 病例的表观遗传年龄加速更高。
