哥斯达黎加成年人中与吸烟相关的全表观基因组关联研究及表观遗传年龄加速

Epigenome-wide association study and epigenetic age acceleration associated with cigarette smoking among Costa Rican adults.

作者信息

Cardenas Andres, Ecker Simone, Fadadu Raj P, Huen Karen, Orozco Allan, McEwen Lisa M, Engelbrecht Hannah-Ruth, Gladish Nicole, Kobor Michael S, Rosero-Bixby Luis, Dow William H, Rehkopf David H

机构信息

Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, 2121 Berkeley Way, #5121, Berkeley, CA, 94720, USA.

UCL Cancer Institute, University College London, London, UK.

出版信息

Sci Rep. 2022 Mar 11;12(1):4277. doi: 10.1038/s41598-022-08160-w.

Smoking-associated DNA methylation (DNAm) signatures are reproducible among studies of mostly European descent, with mixed evidence if smoking accelerates epigenetic aging and its relationship to longevity. We evaluated smoking-associated DNAm signatures in the Costa Rican Study on Longevity and Healthy Aging (CRELES), including participants from the high longevity region of Nicoya. We measured genome-wide DNAm in leukocytes, tested Epigenetic Age Acceleration (EAA) from five clocks and estimates of telomere length (DNAmTL), and examined effect modification by the high longevity region. 489 participants had a mean (SD) age of 79.4 (10.8) years, and 18% were from Nicoya. Overall, 7.6% reported currently smoking, 35% were former smokers, and 57.4% never smoked. 46 CpGs and five regions (e.g. AHRR, SCARNA6/SNORD39, SNORA20, and F2RL3) were differentially methylated for current smokers. Former smokers had increased Horvath's EAA (1.69-years; 95% CI 0.72, 2.67), Hannum's EAA (0.77-years; 95% CI 0.01, 1.52), GrimAge (2.34-years; 95% CI1.66, 3.02), extrinsic EAA (1.27-years; 95% CI 0.34, 2.21), intrinsic EAA (1.03-years; 95% CI 0.12, 1.94) and shorter DNAmTL (- 0.04-kb; 95% CI - 0.08, - 0.01) relative to non-smokers. There was no evidence of effect modification among residents of Nicoya. Our findings recapitulate previously reported and novel smoking-associated DNAm changes in a Latino cohort.

在大多为欧洲血统的研究中，吸烟相关的DNA甲基化（DNAm）特征具有可重复性，但关于吸烟是否会加速表观遗传衰老及其与长寿的关系，证据并不一致。我们在哥斯达黎加长寿与健康老龄化研究（CRELES）中评估了吸烟相关的DNAm特征，该研究包括来自尼科亚长寿地区的参与者。我们测量了白细胞中的全基因组DNAm，测试了五个时钟的表观遗传年龄加速（EAA）和端粒长度（DNAmTL）估计值，并研究了长寿地区的效应修饰。489名参与者的平均（标准差）年龄为79.4（10.8）岁，18%来自尼科亚。总体而言，7.6%的人报告目前吸烟，35%为曾经吸烟者，57.4%从不吸烟。46个CpG位点和五个区域（如AHRR、SCARNA6/SNORD39、SNORA20和F2RL3）在当前吸烟者中存在差异甲基化。与不吸烟者相比，曾经吸烟者的霍瓦斯EAA增加（1.69岁；95%置信区间0.72，2.67），汉纳姆EAA增加（0.77岁；95%置信区间0.01，1.52），GrimAge增加（2.34岁；95%置信区间1.66，3.02），外在EAA增加（1.27岁；95%置信区间0.34，2.21），内在EAA增加（1.03岁；95%置信区间0.12，1.94），DNAmTL缩短（-0.04千碱基；95%置信区间-0.08，-0.01）。没有证据表明尼科亚居民之间存在效应修饰。我们的研究结果概括了先前报道的以及拉丁裔队列中与吸烟相关的新的DNAm变化。