Faculty, Staff and Student Publications
Language
English
Publication Date
10-7-2024
Journal
Human Molecular Genetics
DOI
10.1093/hmg/ddae112
PMID
39079086
PMCID
PMC11458006
PubMedCentral® Posted Date
7-31-2024
PubMedCentral® Full Text Version
Post-print
Abstract
Obesity and poverty disproportionally affect African American persons. Epigenetic mechanisms could partially explain the association between socioeconomic disadvantage and body mass index (BMI). We examined the extent to which epigenetic mechanisms mediate the effect of socioeconomic status (SES) on BMI. Using data from African American adults from the Atherosclerosis Risk in Communities (ARIC) Study (n = 2664, mean age = 57 years), education, income, and occupation were used to create a composite SES score at visit 1 (1987-1989). We conducted two methylation-wide association analyses to identify associations between SES (visit 1), BMI and cytosine-phosphate-guanine (CpG) sites measured at a subsequent visit (1990-1995). We then utilized structural equation modeling (SEM) to test whether identified sites mediated the association between earlier SES and BMI in sex-stratified models adjusted for demographic and risk factor covariates. Independent replication and meta-analyses were conducted using the Jackson Heart Study (JHS, n = 874, mean age 51 years, 2000-2004). Three CpG sites near MAD1L1, KDM2B, and SOCS3 (cg05095590, cg1370865, and cg18181703) were suggestively associated (P-value < 1.3×10-5) in ARIC and at array-wide significance (P-value < 1.3×10-7) in a combined meta-analysis of ARIC with JHS. SEM of these three sites revealed significant indirect effects in females (P-value < 5.8×10-3), each mediating 7%-20% of the total effect of SES on BMI. Nominally significant indirect effects were observed for two sites near MAD1L1 and KDM2B in males (P-value < 3.4×10-2), mediating -17 and -22% of the SES-BMI effect. These results provide further evidence that epigenetic modifications may be a potential pathway through which SES may "get under the skin" and contribute to downstream health disparities.
Keywords
Humans, Female, Male, Black or African American, DNA Methylation, Jumonji Domain-Containing Histone Demethylases, Middle Aged, Body Mass Index, Suppressor of Cytokine Signaling 3 Protein, Nuclear Proteins, CpG Islands, Social Class, F-Box Proteins, Epigenesis, Genetic, Obesity, Adult, Aged, Risk Factors, Genome-Wide Association Study, Cell Cycle Proteins
Published Open-Access
yes
Recommended Citation
Glover, LáShauntá; Lilly, Adam G; Justice, Anne E; et al., "DNA Methylation Near MAD1L1, KDM2B, and SOCS3 Mediates the Effect of Socioeconomic Status on Elevated Body Mass Index in African American Adults" (2024). Faculty, Staff and Student Publications. 1138.
https://digitalcommons.library.tmc.edu/uthsph_docs/1138