Epigenome-wide association study meta-analysis of BMI in African Americans

Despite considerable advances in identifying risk factors for obesity, gaps remain in our understanding about its etiology. Genetic variants explain only a small portion of variation in obesity-related traits such as body mass index (BMI). Epigenetic regulation, which controls gene expression and is influenced by environmental and genetic factors, may account for additional variability in BMI. Epigenetic studies of BMI have largely been conducted in European ancestry populations, despite the disproportionate burden of obesity in African Americans (AAs). We conducted a sex-stratified BMI epigenome-wide association study meta-analysis in AA participants from the Jackson Heart Study (n = 1,604) and the Multi-Ethnic Study of Atherosclerosis (n = 179) with Illumina EPIC (850,000) array data. Linear regression models with methylation as the outcome and continuous BMI as the predictor were stratified by study and sex and meta-analyzed. We identified 208 methylation sites (CpGs, p < 8.72 × 10<sup>-8</sup>) significantly associated with BMI; 151 had not been previously reported in the literature. Replication was performed in a separate sample of AA participants with 450,000 array data, which lacks many CpGs present in the 850,000 array. Replication testing was possible for only 29 of the 151 CpGs; 19 were statistically significant (p < 1.72 × 10<sup>-3</sup>). Sex-specific results showed 4 female-only and 3 male-only BMI-CpGs not identified in the sex-combined results. Differentially methylated region (DMR) analysis resulted in 66 DMRs, including several regions near genes previously implicated for obesity (e.g., SOCS3, TGFB1). Further analyses showed enrichment of genes and traits related to the immune system and inflammation-related pathways (e.g., the IL-6/JAK/STAT pathway).

Authors

Institutions

Publication Details

Journal
Human Genetics and Genomics Advances
Published
2025-12-05
DOI
https://doi.org/10.1016/j.xhgg.2025.100552
Primary Topic
Epigenetics and DNA Methylation
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Epigenome-wide association study meta-analysis of BMI in African Americans

Maggie A. Stanislawski, Sridharan Raghavan, Matthew Allison, Kendra Ferrier et al.
Human Genetics and Genomics Advances
Epigenetics and DNA Methylation
article

Epigenome-wide association study meta-analysis of BMI in African Americans

Maggie A. Stanislawski, Sridharan Raghavan, Matthew Allison, Kendra Ferrier, Audrey E. Hendricks, Kristin L. Young, Laura M. Raffield, Ethan M. Lange, Anne E. Justice, Kari E. North, M. Graff, Joshua J. Joseph, Iain R. Konigsberg, Stephen S. Rich, Silva Kasela, Matthew Jay Budoff, April P. Carson, Heather M. Highland, Leslie A. Lange, Jill M. Norris, Jerome I. Rotter, Charles Kooperberg, Chris Gignoux, Eric Boerwinkle, François Aguet
article en

Abstract

Despite considerable advances in identifying risk factors for obesity, gaps remain in our understanding about its etiology. Genetic variants explain only a small portion of variation in obesity-related traits such as body mass index (BMI). Epigenetic regulation, which controls gene expression and is influenced by environmental and genetic factors, may account for additional variability in BMI. Epigenetic studies of BMI have largely been conducted in European ancestry populations, despite the disproportionate burden of obesity in African Americans (AAs). We conducted a sex-stratified BMI epigenome-wide association study meta-analysis in AA participants from the Jackson Heart Study (n = 1,604) and the Multi-Ethnic Study of Atherosclerosis (n = 179) with Illumina EPIC (850,000) array data. Linear regression models with methylation as the outcome and continuous BMI as the predictor were stratified by study and sex and meta-analyzed. We identified 208 methylation sites (CpGs, p < 8.72 × 10<sup>-8</sup>) significantly associated with BMI; 151 had not been previously reported in the literature. Replication was performed in a separate sample of AA participants with 450,000 array data, which lacks many CpGs present in the 850,000 array. Replication testing was possible for only 29 of the 151 CpGs; 19 were statistically significant (p < 1.72 × 10<sup>-3</sup>). Sex-specific results showed 4 female-only and 3 male-only BMI-CpGs not identified in the sex-combined results. Differentially methylated region (DMR) analysis resulted in 66 DMRs, including several regions near genes previously implicated for obesity (e.g., SOCS3, TGFB1). Further analyses showed enrichment of genes and traits related to the immune system and inflammation-related pathways (e.g., the IL-6/JAK/STAT pathway).

Human Genetics and Genomics AdvancesVol. 7(1)
Broad Institute (US), University of North Carolina at Chapel Hill (US), Colorado School of Public Health (US), UCLA Medical Center (US), The Ohio State University Wexner Medical Center (US), Jackson Memorial Hospital (US), University of Mississippi Medical Center (US), University of California San Diego (US), Fred Hutch Cancer Center (US), New York Genome Center (US), Harbor–UCLA Medical Center (US), University of Virginia (US), University of Colorado Anschutz Medical Campus (US), Geisinger Health System (US), The University of Texas Health Science Center at Houston (US)
Openalex Percentile: Top 65%
Epigenetics and DNA Methylation
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.