利用 4 个时钟指标评估邻里剥夺与表观遗传衰老的关联。

Association of Neighborhood Deprivation With Epigenetic Aging Using 4 Clock Metrics.

机构信息

Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.

Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.

出版信息

JAMA Netw Open. 2020 Nov 2;3(11):e2024329. doi: 10.1001/jamanetworkopen.2020.24329.

DOI:10.1001/jamanetworkopen.2020.24329

PMID:33146735

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7643028/

Abstract

IMPORTANCE: Neighborhood deprivation is associated with age-related disease, mortality, and reduced life expectancy. However, biological pathways underlying these associations are not well understood. OBJECTIVE: To evaluate the association between neighborhood deprivation and epigenetic measures of age acceleration and genome-wide methylation. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the Sister Study, a prospective cohort study comprising 50 884 women living in the US and Puerto Rico aged 35 to 74 years at enrollment who had a sister with breast cancer but had not had breast cancer themselves. Cohort enrollment occurred between July 2003 and March 2009. Participants completed a computer-assisted telephone interview on demographic, socioeconomic, lifestyle, and residential factors and provided anthropometric measures and peripheral blood samples at a home examination. DNA methylation data obtained for 2630 non-Hispanic White women selected for a case-cohort study in 2014 were used in this cross-sectional analysis. DNA methylation was measured using the HumanMethylation450 BeadChips in whole blood samples collected at baseline. Data analysis for this study was performed from October 17, 2019, to August 27, 2020. EXPOSURES: Each participants' primary address was linked to an established index of neighborhood deprivation. MAIN OUTCOMES AND MEASURES: Epigenetic age was estimated using 4 epigenetic clocks (Horvath, Hannum, PhenoAge, and GrimAge). Age acceleration was determined using residuals from regressing chronologic age on each of the 4 epigenetic age metrics. Linear regression was used to estimate associations between neighborhood deprivation and epigenetic age acceleration as well as DNA methylation at individual cytosine-guanine sites across the genome. RESULTS: Mean (SD) age of the 2630 participants was 56.9 (8.7) years. Those with the greatest (>75th percentile) vs least (≤25th percentile) neighborhood deprivation had higher epigenetic age acceleration estimated by Hannum (β = 0.23; 95% CI, 0.01-0.45), PhenoAge (β = 0.28; 95% CI, 0.06-.50), and GrimAge (β = 0.37; 95% CI, 0.12-0.62). Increasing US quartiles of neighborhood deprivation exhibited a trend with Hannum, PhenoAge, and GrimAge. For example, GrimAge showed a significant dose-response (P test for trend <.001) as follows: level 2 vs level 1 (β = 0.30; 95% CI, 0.17-0.42), level 3 vs level 1 (β = 0.35; 95% CI, 0.19-0.50), and level 4 vs level 1 (β = 0.37; 95% CI, 0.12-0.62). Neighborhood deprivation was found to be associated with 3 cytosine-phosphate-guanine sites, with 1 of these annotated to a known gene MAOB (P = 9.71 × 10-08). CONCLUSIONS AND RELEVANCE: The findings of this study suggest that residing in a neighborhood with a higher deprivation index appears to be reflected by methylation-based markers of aging.

摘要

重要性：贫困社区与年龄相关的疾病、死亡率和预期寿命缩短有关。然而，这些关联的生物学途径尚不清楚。

目的：评估贫困社区与年龄加速的表观遗传测量和全基因组甲基化之间的关联。

设计、设置和参与者：这项横断面研究使用了来自姐妹研究的数据，这是一项包括居住在美国和波多黎各的 50884 名年龄在 35 至 74 岁之间的女性的前瞻性队列研究。这些女性的姐姐患有乳腺癌，但本人没有患乳腺癌。队列招募于 2003 年 7 月至 2009 年 3 月进行。参与者通过计算机辅助电话访谈完成了有关人口统计学、社会经济、生活方式和居住因素的问卷调查，并在家庭检查时提供了人体测量学测量值和外周血样。2014 年在一项病例-对照研究中选择的 2630 名非西班牙裔白人女性的 DNA 甲基化数据用于本横断面分析。使用全血样本中的 HumanMethylation450 BeadChips 测量 DNA 甲基化，这些样本是在基线时采集的。本研究的数据分析于 2019 年 10 月 17 日至 2020 年 8 月 27 日进行。

暴露：每位参与者的主要住址都与既定的社区贫困指数相联系。

主要结果和措施：使用 4 个表观遗传时钟（Horvath、Hannum、PhenoAge 和 GrimAge）估计表观遗传年龄。通过将实际年龄回归到每个表观遗传年龄指标上来确定年龄加速。使用线性回归来估计社区贫困与表观遗传年龄加速以及全基因组中单个胞嘧啶-磷酸-鸟嘌呤位点的 DNA 甲基化之间的关联。

结果： 2630 名参与者的平均（标准差）年龄为 56.9（8.7）岁。那些处于最贫困（>第 75 个百分位）和最富裕（≤第 25 个百分位）社区的人，其表观遗传年龄加速由 Hannum（β=0.23；95%置信区间，0.01-0.45）、PhenoAge（β=0.28；95%置信区间，0.06-0.50）和 GrimAge（β=0.37；95%置信区间，0.12-0.62）估计的更高。美国社区贫困程度每增加一个四分位数，Hannum、PhenoAge 和 GrimAge 均呈现出一种趋势。例如，GrimAge 显示出显著的剂量反应（趋势检验 P<0.001），具体如下：第 2 级与第 1 级（β=0.30；95%置信区间，0.17-0.42）、第 3 级与第 1 级（β=0.35；95%置信区间，0.19-0.50）和第 4 级与第 1 级（β=0.37；95%置信区间，0.12-0.62）。研究发现，有 3 个胞嘧啶-磷酸-鸟嘌呤位点与社区贫困有关，其中 1 个位点注释到已知基因 MAOB（P=9.71×10-08）。

结论和相关性：这项研究的结果表明，生活在贫困程度较高的社区似乎会反映在基于甲基化的衰老标志物上。