Investigation of psychosocial stress and DNA methylation in genes related to immune response, metabolism, and calcium signaling among African American and White middle-aged adults

Abstract Chronic psychological stress is an environmental factor associated with chronic disease risk and health disparities. Since environmental stressors alter gene expression and physiologic responses through epigenetic mechanisms, perceived discrimination (PD) or the subjective experience of receiving negative treatment related to personal characteristics may influence DNA methylation (DNAm) of CpGs within genes linked to chronic disease. Using the Illumina 850K EPIC chip and psychosocial stress associated discrimination scales including the Lifetime, Racial, and Everyday Discrimination scales, we identified novel CpGs and differentially methylated positions (DMPs) associated with PD in the context of age, sex, and poverty status among African American and White adults and ones that overlap previous findings of differentially methylated sites (or genes) with discrimination, inflammation and chronic disease. Ingenuity Pathway Analysis (IPA) identified several pathways associated with the DNAm patterns and PD with age, sex, and/or poverty status. With age, the white adipose tissue browning pathway was activated among African American participants. This was related to the differential methylation found in the CACNA1H, PRDM16, and BDNF genes. Among White participants, the opioid signaling pathway was activated and significantly enriched for the genes FGR, POMC, and RPS6KA2. Additionally, CpG sites associated with PD among White participants with poverty status revealed that the netrin signaling, opioid signaling, and calcium signaling pathways were activated and significantly enriched for differentially methylated genes including NFATC1 and NFATC2. The identified novel DNAm genes associated with PD transduce effects through biological pathways related to inflammation and immune response, white adipose tissue browning, and calcium signaling.