Browsing by Author "Fuemmeler, Bernard F"
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Item Open Access An epigenome-wide association study of child appetitive traits and DNA methylation.(Appetite, 2023-10) Harris, Holly A; Friedman, Chloe; Starling, Anne P; Dabelea, Dana; Johnson, Susan L; Fuemmeler, Bernard F; Jima, Dereje; Murphy, Susan K; Hoyo, Cathrine; Jansen, Pauline W; Felix, Janine F; Mulder, Rosa HThe etiology of childhood appetitive traits is poorly understood. Early-life epigenetic processes may be involved in the developmental programming of appetite regulation in childhood. One such process is DNA methylation (DNAm), whereby a methyl group is added to a specific part of DNA, where a cytosine base is next to a guanine base, a CpG site. We meta-analyzed epigenome-wide association studies (EWASs) of cord blood DNAm and early-childhood appetitive traits. Data were from two independent cohorts: the Generation R Study (n = 1,086, Rotterdam, the Netherlands) and the Healthy Start study (n = 236, Colorado, USA). DNAm at autosomal methylation sites in cord blood was measured using the Illumina Infinium HumanMethylation450 BeadChip. Parents reported on their child's food responsiveness, emotional undereating, satiety responsiveness and food fussiness using the Children's Eating Behaviour Questionnaire at age 4-5 years. Multiple regression models were used to examine the association of DNAm (predictor) at the individual site- and regional-level (using DMRff) with each appetitive trait (outcome), adjusting for covariates. Bonferroni-correction was applied to adjust for multiple testing. There were no associations of DNAm and any appetitive trait when examining individual CpG-sites. However, when examining multiple CpGs jointly in so-called differentially methylated regions, we identified 45 associations of DNAm with food responsiveness, 7 associations of DNAm with emotional undereating, 13 associations of DNAm with satiety responsiveness, and 9 associations of DNAm with food fussiness. This study shows that DNAm in the newborn may partially explain variation in appetitive traits expressed in early childhood and provides preliminary support for early programming of child appetitive traits through DNAm. Investigating differential DNAm associated with appetitive traits could be an important first step in identifying biological pathways underlying the development of these behaviors.Item Open Access Associations of Alcohol and Tobacco Retail Outlet Rates with Neighborhood Disadvantage.(International journal of environmental research and public health, 2022-01-20) Wheeler, David C; Boyle, Joseph; Barsell, D Jeremy; Glasgow, Trevin; McClernon, F Joseph; Oliver, Jason A; Fuemmeler, Bernard FTobacco causes 29% of cancer-related deaths while alcohol causes 5.5% of cancer-related deaths. Reducing the consumption of these cancer-causing products is a special priority area for the National Cancer Institute. While many factors are linked to tobacco and alcohol use, the placement and density of retail outlets within neighborhoods may be one community-level risk factor contributing to greater use of these products. To elucidate associations between tobacco, alcohol, and tobacco and alcohol retail outlets (TRO, ARO, and TARO) and neighborhood disadvantage over a large geographic area, we employed a novel Bayesian index modeling approach to estimate a neighborhood disadvantage index (NDI) and its associations with rates of the three types of retailers across block groups in the state of North Carolina. We used a novel extension of the Bayesian index model to include a shared component for the spatial pattern common to all three types of outlets and NDI effects that varied by outlet type. The shared component identifies areas that are elevated in risk for all outlets. The results showed significant positive associations between neighborhood disadvantage and TROs (relative risk (RR) = 1.12, 95% credible interval (CI = 1.09, 1.14)) and AROs (RR = 1.15, 95% CI = 1.11, 1.17), but the association was greatest for TAROs (RR = 1.21, 95% CI = 1.18, 1.24). The most important variables in the NDI were percent renters (i.e., low home ownership), percent of homes built before 1940 (i.e., old housing stock), and percent without a high school diploma (i.e., low education).Item Open Access DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study.(Environmental health perspectives, 2021-05-19) Fuemmeler, Bernard F; Dozmorov, Mikhail G; Do, Elizabeth K; Zhang, Junfeng Jim; Grenier, Carole; Huang, Zhiqing; Maguire, Rachel L; Kollins, Scott H; Hoyo, Cathrine; Murphy, Susan KBackground
Maternal smoking during pregnancy is related to altered DNA methylation in infant umbilical cord blood. The extent to which low levels of smoke exposure among nonsmoking pregnant women relates to offspring DNA methylation is unknown.Objective
This study sought to evaluate relationships between maternal prenatal plasma cotinine levels and DNA methylation in umbilical cord blood in newborns using the Infinium HumanMethylation 450K BeadChip.Methods
Participants from the Newborn Epigenetics Study cohort who reported not smoking during pregnancy had verified low levels of cotinine from maternal prenatal plasma (0 ng/mL to <4 ng/mL), and offspring epigenetic data from umbilical cord blood were included in this study (n=79). Multivariable linear regression models were fit to the data, controlling for cell proportions, age, race, education, and parity. Estimates represent changes in response to any 1-ng/mL unit increase in exposure.Results
Multivariable linear regression models yielded 29,049 CpGs that were differentially methylated in relation to increases in cotinine at a 5% false discovery rate. Top CpGs were within or near genes involved in neuronal functioning (PRKG1, DLGAP2, BSG), carcinogenesis (FHIT, HSPC157) and inflammation (AGER). Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggest cotinine was related to methylation of gene pathways controlling neuronal signaling, metabolic regulation, cell signaling and regulation, and cancer. Further, enhancers associated with transcription start sites were enriched in altered CpGs. Using an independent sample from the same study population (n=115), bisulfite pyrosequencing was performed with infant cord blood DNA for two genes within our top 20 hits (AGER and PRKG1). Results from pyrosequencing replicated epigenome results for PRKG1 (cg17079497, estimate=-1.09, standard error (SE)=0.45, p=0.018) but not for AGER (cg09199225; estimate=-0.16, SE=0.21, p=0.44).Discussion
Secondhand smoke exposure among nonsmoking women may alter DNA methylation in regions involved in development, carcinogenesis, and neuronal functioning. These novel findings suggest that even low levels of smoke exposure during pregnancy may be sufficient to alter DNA methylation in distinct sites of mixed umbilical cord blood leukocytes in pathways that are known to be altered in cord blood from pregnant active smokers. https://doi.org/10.1289/EHP8099.Item Open Access Maternal stress, preterm birth, and DNA methylation at imprint regulatory sequences in humans.(Genetics & epigenetics, 2014-01) Vidal, Adriana C; Benjamin Neelon, Sara E; Liu, Ying; Tuli, Abbas M; Fuemmeler, Bernard F; Hoyo, Cathrine; Murtha, Amy P; Huang, Zhiqing; Schildkraut, Joellen; Overcash, Francine; Kurtzberg, Joanne; Jirtle, Randy L; Iversen, Edwin S; Murphy, Susan KIn infants exposed to maternal stress in utero, phenotypic plasticity through epigenetic events may mechanistically explain increased risk of preterm birth (PTB), which confers increased risk for neurodevelopmental disorders, cardiovascular disease, and cancers in adulthood. We examined associations between prenatal maternal stress and PTB, evaluating the role of DNA methylation at imprint regulatory regions. We enrolled women from prenatal clinics in Durham, NC. Stress was measured in 537 women at 12 weeks of gestation using the Perceived Stress Scale. DNA methylation at differentially methylated regions (DMRs) associated with H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, and PLAGL1 was measured from peripheral and cord blood using bisulfite pyrosequencing in a sub-sample of 79 mother-infant pairs. We examined associations between PTB and stress and evaluated differences in DNA methylation at each DMR by stress. Maternal stress was not associated with PTB (OR = 0.98; 95% CI, 0.40-2.40; P = 0.96), after adjustment for maternal body mass index (BMI), income, and raised blood pressure. However, elevated stress was associated with higher infant DNA methylation at the MEST DMR (2.8% difference, P < 0.01) after adjusting for PTB. Maternal stress may be associated with epigenetic changes at MEST, a gene relevant to maternal care and obesity. Reduced prenatal stress may support the epigenomic profile of a healthy infant.Item Open Access Pre-Pregnancy Weight and Symptoms of Attention Deficit Hyperactivity Disorder and Executive Functioning Behaviors in Preschool Children.(International journal of environmental research and public health, 2019-02-25) Fuemmeler, Bernard F; Zucker, Nancy; Sheng, Yaou; Sanchez, Carmen E; Maguire, Rachel; Murphy, Susan K; Kollins, Scott H; Hoyo, CathrineThis study examines pre-pregnancy Body Mass Index (BMI) and gestational weight gain (GWG) in relation to early childhood Attention Deficit Hyperactivity Disorder (ADHD) symptoms and related executive self-regulation behaviors. The analyses sample (n = 331) included a subsample of participants from a birth cohort recruited from prenatal clinics and hospital facilities from April 2005 to June 2011 in Durham, North Carolina. Pre-pregnancy BMI was calculated from weight at the last menstrual period and height was extracted from medical records. Gestational weight gain was calculated from pre-pregnancy weight and weight measured at the time of delivery. ADHD symptoms and executive self-regulation behaviors were assessed by maternal report (mean age = 3 years). Multivariable regression methods with inverse probability weighting (IPW) were used to evaluate associations accounting for sample selection bias and confounding. Pre-pregnancy BMI at levels ≥35 was positively associated with higher ADHD symptoms and worse executive self-regulation behaviors (inhibitory control and attention). Compared to adequate GWG, less than adequate GWG was related to more ADHD hyperactive-impulsive symptoms, whereas greater than adequate GWG was related to more problematic behaviors related to working memory and planning. The findings support a link between maternal weight and child neurodevelopment. Continued research that help identify biological mechanisms are needed.Item Open Access Spatially Varying Associations of Neighborhood Disadvantage with Alcohol and Tobacco Retail Outlet Rates.(International journal of environmental research and public health, 2022-04-26) Wheeler, David C; Boyle, Joseph; Barsell, D Jeremy; Glasgow, Trevin; McClernon, F Joseph; Oliver, Jason A; Fuemmeler, Bernard FMore than 30% of cancer related deaths are related to tobacco or alcohol use. Controlling and restricting access to these cancer-causing products, especially in communities where there is a high prevalence of other cancer risk factors, has the potential to improve population health and reduce the risk of specific cancers associated with these substances in more vulnerable population subgroups. One policy-driven method of reducing access to these cancer-causing substances is to regulate where these products are sold through the placement and density of businesses selling tobacco and alcohol. Previous work has found significant positive associations between tobacco, alcohol, and tobacco and alcohol retail outlets (TRO, ARO, TARO) and a neighborhood disadvantage index (NDI) using Bayesian shared component index modeling, where NDI associations differed across outlet types and relative risks varied by population density (e.g., rural, suburban, urban). In this paper, we used a novel Bayesian index model with spatially varying effects to explore spatial nonstationarity in NDI effects for TROs, AROs, and TAROs across census tracts in North Carolina. The results revealed substantial variation in NDI effects that varied by outlet type. However, all outlet types had strong positive effects in one coastal area. The most important variables in the NDI were percent renters, Black racial segregation, and the percentage of homes built before 1940. Overall, more disadvantaged areas experienced a greater neighborhood burden of outlets selling one or both of alcohol and tobacco.Item Open Access Steps to Health employee weight management randomized control trial: short-term follow-up results.(J Occup Environ Med, 2015-02) Østbye, Truls; Stroo, Marissa; Brouwer, Rebecca JN; Peterson, Bercedis L; Eisenstein, Eric L; Fuemmeler, Bernard F; Joyner, Julie; Gulley, Libby; Dement, John MOBJECTIVE: To present the short-term follow-up findings of the Steps to Health study, a randomized trial to evaluate the effectiveness of two employee weight management programs offered within Duke University and the Health System. METHODS: A total of 550 obese (body mass index, ≥30 kg/m2) employees were randomized 1:1 between January 2011 and June 2012 to the education-based Weight Management (WM) or the WM+ arm, which focused on behavior modification. Employees were contacted to complete a follow-up visit approximately 14 months after baseline. RESULTS: There were no clinically, or statistically, meaningful differences between arms, but there were modest reductions in body mass index, and positive, meaningful changes in diet and physical activity for both arms. CONCLUSIONS: The modest positive effects observed in this study may suggest that to achieve weight loss through the workplace more intensive interventions may be required.