Influence of socioeconomic status on the whole blood transcriptome in African Americans.

Abstract

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.