National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States of America.
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States of America.
PLoS One. 2017 Dec 5;12(12):e0187290. doi: 10.1371/journal.pone.0187290. eCollection 2017.
The correlation between low socioeconomic status (SES) and poor health outcome or higher risk of disease has been consistently reported by many epidemiological studies across various race/ancestry groups. However, the biological mechanisms linking low SES to disease and/or disease risk factors are not well understood and remain relatively under-studied. The analysis of the blood transcriptome is a promising window for elucidating how social and environmental factors influence the molecular networks governing health and disease. To further define the mechanistic pathways between social determinants and health, this study examined the impact of SES on the blood transcriptome in a sample of African-Americans.
An integrative approach leveraging three complementary methods (Weighted Gene Co-expression Network Analysis, Random Forest and Differential Expression) was adopted to identify the most predictive and robust transcriptome pathways associated with SES. We analyzed the expression of 15079 genes (RNA-seq) from whole blood across 36 samples.
The results revealed a cluster of 141 co-expressed genes over-expressed in the low SES group. Three pro-inflammatory pathways (IL-8 Signaling, NF-κB Signaling and Dendritic Cell Maturation) are activated in this module and over-expressed in low SES. Random Forest analysis revealed 55 of the 141 genes that, collectively, predict SES with an area under the curve of 0.85. One third of the 141 genes are significantly over-expressed in the low SES group.
Lower SES has consistently been linked to many social and environmental conditions acting as stressors and known to be correlated with vulnerability to chronic illnesses (e.g. asthma, diabetes) associated with a chronic inflammatory state. Our unbiased analysis of the blood transcriptome in African-Americans revealed evidence of a robust molecular signature of increased inflammation associated with low SES. The results provide a plausible link between the social factors and chronic inflammation.
许多流行病学研究在不同种族/祖先群体中一致报告了低社会经济地位(SES)与健康结果不佳或疾病风险较高之间的相关性。然而,将低 SES 与疾病和/或疾病风险因素联系起来的生物学机制尚未得到很好的理解,并且相对研究不足。血液转录组的分析是阐明社会和环境因素如何影响控制健康和疾病的分子网络的一个很有前途的窗口。为了进一步确定社会决定因素与健康之间的机制途径,本研究在非裔美国人样本中检查了 SES 对血液转录组的影响。
采用三种互补方法(加权基因共表达网络分析、随机森林和差异表达)的综合方法,确定与 SES 最相关和最稳健的转录组途径。我们分析了 36 个样本中全血中 15079 个基因的表达(RNA-seq)。
结果显示,低 SES 组中过表达的 141 个共表达基因簇。三个促炎途径(IL-8 信号、NF-κB 信号和树突状细胞成熟)在该模块中被激活并在低 SES 中过表达。随机森林分析显示,141 个基因中有 55 个基因共同预测 SES,曲线下面积为 0.85。这 141 个基因中有三分之一在低 SES 组中显著过表达。
低 SES 一直与许多作为应激源的社会和环境条件相关联,并且已知与与慢性炎症状态相关的慢性疾病(如哮喘、糖尿病)的易感性相关。我们对非裔美国人血液转录组的无偏分析显示,与低 SES 相关的炎症增强的稳健分子特征的证据。结果为社会因素与慢性炎症之间提供了一个合理的联系。