Summary Obesity is associated with widespread differential DNA methylation (DNAm) patterns, though there have been limited overlap in the obesity‐associated cytosine–guanine nucleotide pair (CpG) sites that have been identified in the literature. We systematically searched four databases for studies published until January 2020. Eligible studies included cross‐sectional, longitudinal, or intervention studies examining adiposity and genome‐wide DNAm in non‐pregnant adults aged 18–75 in all tissue types. Study design and results were extracted in the descriptive review. Blood‐based DNAm results in body mass index (BMI) and waist circumference (WC) were meta‐analyzed using weighted sum of Z‐score meta‐analysis. Of the 10,548 studies identified, 46 studies were included in the systematic review with 18 and nine studies included in the meta‐analysis of BMI and WC, respectively. In the blood, 77 and four CpG sites were significant in three or more studies of BMI and WC, respectively. Using a genome‐wide threshold for significance, 52 blood‐based CpG sites were significantly associated with BMI. These sites have previously been associated with many obesity‐related diseases including type 2 diabetes, cardiovascular disease, Crohn's disease, and depression. Our study shows that DNAm at 52 CpG sites represent potential mediators of obesity‐associated chronic diseases and may be novel intervention or therapeutic targets to protect against obesity‐associated chronic diseases.
Background Neighborhood disadvantage may impact risk of preterm birth through stress. Few studies have examined how neighborhood disadvantage relates to stress during pregnancy, especially for Black women. Methods Secondary data analysis of 572 women in a prospective cohort in Detroit, MI and Columbus, OH. Participants completed questionnaires including the ROSS Neighborhood Disorder Scale, the crime subscale of the Perceived Neighborhood Scale (PNS), and the Perceived Stress Scale. An objective neighborhood disadvantage index (NDI) was created using principal components analysis after geocoding residential addresses and linking to Census data. Results All models used logistic regression. Adjusted for maternal age and annual household income, perceived stress was positively associated with perceived neighborhood disorder (p < .01). In a separate model, perceived neighborhood crime was positively associated with perceived neighborhood disorder (p = .005). In a joint model adjusted for age and income, the association of disorder with stress was similar in magnitude (p < .01) but the association between crime and stress weakened. The NDI was not associated with perceived stress before or after adjustment for confounders. Conclusions Perceived neighborhood disadvantage may capture a different dimension than objective neighborhood disadvantage. Future studies should test stress as a pathway by which neighborhood environment increases risk of preterm birth.
Background: Structural racism has been associated with breast cancer mortality. Exposure to adverse inequities may drive epigenetic perturbations that affect racial disparities in breast cancer outcomes. This study examined the association between neighborhood-level redlining and DNA methylation in non-Hispanic Black and White women diagnosed with breast cancer. Methods: Genome-wide DNA methylation was measured using the EPIC array in the tumor tissue of 84 women. Linear regression models were used to examine the association between neighborhood-level redlining and methylation, regressing β values for each cytosine-phosphate-guanine dinucleotide (CpG) site on redlining while adjusting for covariates. Redlining was derived for census tracts using the Home Mortgage Disclosure Act database. We used a false discovery rate (FDR) threshold <0.1, and for CpGs below this threshold, we examined interactions with Estrogen Receptor (ER) status. We employed multivariable Cox-proportional hazard models to estimate whether aberrant methylation was associated with all-cause mortality. Results: 36 of the CpG sites were associated with neighborhood-level redlining (FDR<0.1). The majority of genes are implicated in carcinogenesis including genes in immune function (BANP, IGDCC3, GPR15), oncogenic signaling (IGFALS, RNLS, RTP3), and angiogenesis (ANGPT1). Further exploration of these 36 CpG sites revealed no interactions by ER status, no probes were associated with all-cause mortality. Conclusions: We identified novel associations between neighborhood-level redlining and the breast tumor DNA methylome. Our data are the first to show that structural racism impacts the breast tumor epigenome. Citation Format: Jasmine M Miller-Kleinhenz, Leah Moubadder, Kirsten M. Beyer, Yuhong Zhou, Anne H. Gaglioti, Jazib Gohar, Lindsay J. Collin, Kashari Henry, Karen M. Conneely, Uma Krishnamurti, Olivia D'Angelo, Keerthi Gogineni, Mylin Torres, Sheryl Gabram-Mendola, Lauren E. McCullough. Neighborhood-level redlining-associated methylation in breast tumors: The impact of structural racism on the tumor epigenome [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR-03.
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