Differential impact of cumulative SES risk on methylation of protein-protein interaction pathways as a function of SLC6A4 genetic variation in African American young adults

Abstract

Exposure to cumulative SES risk in childhood may interact with variability at the serotonin transporter linked polymorphic region (5HTTLPR) to alter DNA methylation across interacting sets of proteins. DNA was obtained from 388 African Americans at age 19. Genotype at the 5HTTLPR was determined, and methylation ratios for C-phosphate-G (CpG) residues were assessed. Exposure to cumulative SES risk was determined using repeated parental reports at ages 11-13. At high SES risk, CpG methylation patterns indicated altered cellular stress response in women, but not men, who carried a short allele at the 5HTTLPR. These changes in methylation patterns may lead to increases in mental and physical health risks. No genotype effect emerged for either women or men at low SES risk. Methylation patterns provide guidance in identifying pathways by which genetic susceptibility is transformed into adverse outcomes years later.

Keywords: 5HTTLPR; Gene×environment interaction; Health; Resources; Susceptibility.

Fig. 1

The most significant protein sub-network (p-value approximately 0) consists of 6 proteins. The central node is CD3D. Node colors represent the negative log p-value from the t-test between female s-allele carriers and non-s-allele carriers in the presence of cumulative stress after correction for multiple comparisons. Line thickness between nodes represents strength of interaction between proteins. Subnetwork enriched for pathway involved with cellular response to unfolded proteins and stress. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)