Epigenetic Mediators Between Childhood Socioeconomic Disadvantage and Mid-Life Body Mass Index: The New England Family Study.
ABSTRACT: OBJECTIVE:Childhood socioeconomic disadvantage is associated with adulthood obesity risk; however, epigenetic mechanisms are poorly understood. This work's objective was to evaluate whether associations of childhood socioeconomic disadvantage with adulthood body mass index (BMI) are mediated by DNA methylation. METHODS:Participants were 141 men and women from the New England Family Study, prospectively followed prenatally through a mean age of 47 years. Epigenomewide DNA methylation was evaluated in peripheral blood and adipose tissue obtained at adulthood, using the Infinium HumanMethylation450K BeadChip. Childhood socioeconomic status (SES) at age 7 years was assessed directly from parents' reports. Offspring adiposity was directly assessed using BMI at a mean age of 47 years. Associations of SES, DNA methylation, and BMI were estimated using least square estimators. Statistical mediation analyses were performed using joint significance test and bootstrapping. RESULTS:Of CpG sites significant at the 25% false discovery rate level in epigenomewide methylation BMI analyses, 91 sites in men and 71 sites in women were additionally significant for SES-methylation associations (p < .001) in adipose tissue. Many involved genes biologically relevant for development of obesity, including fatty acid synthase, transmembrane protein 88, signal transducer and activator of transcription 3, and neuritin 1. There was no evidence of epigenetic mediation in peripheral blood leukocytes. CONCLUSIONS:DNA methylation at specific genes may be mediators of associations between childhood socioeconomic disadvantage and mid-life BMI in adipose tissue. Findings motivate continued efforts to study if and how childhood socioeconomic disadvantage is biologically embedded at the level of the epigenome in regions etiologically relevant for adiposity.
Project description:<h4>Background</h4>Early exposure to socioeconomic disadvantage is associated with obesity. Here we investigated how early, and conducted mediation analyses to identify behavioural factors in adulthood that could explain why.<h4>Methods</h4>Among 931 participants in the New England Family Study, we investigated the associations of family socioeconomic disadvantage measured before birth and at age 7 years with the following measures of adiposity in mid-adulthood (mean age?=?44.4?years): body mass index (BMI), waist circumference and, among 400 participants, body composition from dual-energy X-ray absorption scans.<h4>Results</h4>In linear regressions adjusting for age, sex, race and childhood BMI Z-score, participants in the highest tertile of socioeconomic disadvantage at birth had 2.6 additional BMI units in adulthood [95% confidence interval (CI)?=?1.26, 3.96], 5.62 cm waist circumference (95% CI?=?2.69, 8.55), 0.73 kg of android fat mass (95% CI?=?0.25, 1.21), and 7.65 higher Fat Mass Index (95% CI?=?2.22, 13.09). Conditional on disadvantage at birth, socioeconomic disadvantage at age 7 years was not associated with adult adiposity. In mediation analyses, 10-20% of these associations were explained by educational attainment and 5-10% were explained by depressive symptoms.<h4>Conclusions</h4>Infancy may be a sensitive period for exposure to socioeconomic disadvantage, as exposure in the earliest years of life confers a larger risk for overall and central adiposity in mid-adulthood than exposure during childhood. Intervention on these two adult risk factors for adiposity would, if all model assumptions were satisfied, only remediate up to one-fifth of the excess adult adiposity among individuals born into socioeconomically disadvantaged households.
Project description:Childhood socioeconomic status (SES) is related to risk for cardiovascular disease in adulthood, perhaps, in part, due to associations with inflammatory and hemostasis processes. We tested the hypotheses that childhood SES is related to C-reactive protein (CRP), fibrinogen, factor VIIc, and plasminogen activator inhibitor-1 (PAI-1) in midlife women and that the associations are mediated by adult SES and/or adult body mass index (BMI).Using data from the prospective Study of Women's Health Across the Nation, we classified 1067 black and white women into 3 multidimensional childhood SES groups based on latent class analysis. Biological measures were assessed across 7 years along with covariates and mediators and analyzed by mixed regression models, followed by tests for mediation.Compared with women raised in high SES families, those from the lowest SES families had higher levels of CRP (b [standard error] = 0.37 [0.11]), PAI-1 (b = 0.23 [0.07]) factor VIIc (b = 0.05 [0.02]), and fibrinogen (b = 11.06 [4.89]), after adjustment for ethnicity, site, age, ratings of health between ages 11 and 18 years, visit, smoking status, menopausal status, stroke or heart attack, medications, and hormone use. Introduction of adult SES and BMI into the models reduced the childhood SES associations to nonsignificance for all four measures. Indirect mediation was apparent for adult education and BMI for CRP, and BMI for PAI-1.Women raised in lower SES families had elevated markers of inflammation and hemostasis, in part, due to elevated BMI and education in adulthood.
Project description:We investigate whether childhood exposures influence adult chronic inflammation and mortality risk via adult health characteristics and socioeconomic status (SES) and whether gender moderates these relationships. Analyzing a longitudinal national sample of 9,310 men and women over age 50, we found that childhood SES, parental behaviors, and adolescent behaviors were associated with adult chronic inflammation via health characteristics and SES in adulthood. The process of disadvantage initiated by low childhood SES (i.e., adult health risk factors, socioeconomic disadvantage, and chronic inflammation) subsequently raised mortality risk. In addition, gender moderated the mediating influence of childhood SES via unhealthy behaviors and parental behaviors via adult SES. Demonstrating how social forces shape biological health through multiple mechanisms informs health policies by identifying multiple points of intervention in an effort to reduce the lasting consequences of childhood disadvantage.
Project description:Children raised in families with low socioeconomic status (SES) go on to have high rates of chronic illness in adulthood. However, a sizable minority of low-SES children remain healthy across the life course, which raises questions about the factors associated with, and potentially responsible for, such resilience. Using a sample of 1,205 middle-aged Americans, we explored whether two characteristics--upward socioeconomic mobility and early parental nurturance--were associated with resilience to the health effects of childhood disadvantage. The primary outcome in our analyses was the presence of metabolic syndrome in adulthood. Results revealed that low childhood SES was associated with higher prevalence of metabolic syndrome at midlife, independently of traditional risk factors. Despite this pattern, half the participants raised in low-SES households were free of metabolic syndrome at midlife. Upward social mobility was not associated with resilience to metabolic syndrome. However, results were consistent with a buffering scenario, in which high levels of maternal nurturance offset the metabolic consequences of childhood disadvantage.
Project description:Longitudinal studies drawn from high-income countries demonstrate long-term associations of early childhood socioeconomic deprivation with increased adiposity in adulthood. However, there are very few data from resource-poor countries where there are reasons to anticipate different gradients. Accordingly, we sought to characterise the nature of the socioeconomic status (SES)-adiposity association in Brazil.We use data from the Ribeirao Preto Cohort Study in Brazil in which 9067 newborns were recruited via their mothers in 1978/79 and one-in-three followed up in 2002/04 (23-25years). SES, based on family income (salaries, interest on savings, pensions and so on), was assessed at birth and early adulthood, and three different adiposity measures (body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR)) ascertained at follow-up. The association between childhood SES, adult SES and social mobility (defined as four permutations of SES in childhood and adulthood: low-low, low-high, high-low, high-high), and the adiposity measures was examined using linear regression.There was evidence that the association between SES and the three markers of adiposity was modified by gender in both adulthood (P<0.02 for all outcomes) and childhood SES (P<0.02 for WC and WHR). Thus, in an unadjusted model, linear regression analyses showed that higher childhood SES was associated with lower adiposity in women (coefficient (95% confidence intervals) BMI: -1.49 (-2.29,-0.69); WC: -3.85 (-5.73,-1.97); WHR: -0.03 (-0.04,-0.02)). However, in men, higher childhood SES was related to higher adiposity (BMI: 1.03 (0.28,-1.78); WC: 3.15 (1.20, 5.09); WHR: 0.009 (-0.001, 0.019)) although statistical significance was not seen in all analyses. There was a suggestion that adult SES (but not adult health behaviours or birthweight) accounted for these relationships in women only. Upward mobility was associated with protection against greater adiposity in women but not men.In the present study, in men there was some evidence that both higher childhood and adulthood SES was related to a higher adiposity risk, while the reverse gradient was apparent in women.
Project description:AIM:The objective of this study was to identify potential epigenetic mediating pathways linking early life social disadvantage (ELSD) to adulthood BMI. METHODS:Sex-specific epigenome-wide two-stage mediation analyses were conducted in blood and adipose tissue, and mediation estimates were obtained using cross-product mediation analysis. Pathway analyses were conducted using GREAT software (Bejerano Lab, CA, USA). RESULTS:Candidate mediation CpG sites were identified in adipose tissue, but not blood, and were sex-specific. Significant mediation sites in females included CpG loci in genes: PKHG1, BCAR3, ADAM5P, PIEZO1, FGFRL1, FASN and DPP9, among others. Pathway analyses revealed evidence of enrichment for processes associated with TFG-? signaling and immunologic signatures. In males, significant mediation loci included sites in MAP3K5 and RPTOR, which have previously been associated with adipogenesis, inflammation and insulin resistance. CONCLUSION:Our findings provide supportive evidence for the mediating role of epigenetic mechanisms in the effect of early life social disadvantage on adulthood BMI.
Project description:Objectives:A growing literature acknowledges the association between childhood socioeconomic status (SES) and health in late adulthood (i.e., 50+). Less, however, is known about the association with mental health outcomes, such as depression. We use the Survey on Health, Ageing, and Retirement in Europe (SHARE) to analyze overall and gender-specific associations between childhood SES and late-adulthood depression. Methods:Using life history and contemporaneous data from 21,989 SHARE respondents in combination with principal component analysis we construct indices of childhood SES. We measure late-adulthood depression using the EURO-D scale. Contemporaneous SES is operationalized as the logarithm of household equivalized income. We estimate associations using linear regression models. Results:We document a positive association between childhood SES and the late-adulthood EURO-D score. The association persists even when allowing for contemporaneous SES. Zooming in on gender-specific associations reveals that the association for mental health is particularly pronounced for women. Discussion:Our findings reveal the long-term association between childhood socioeconomic conditions and depression later in life, which persists even after taking into account current socioeconomic conditions and are stronger for women than for men. These results imply that boosting childhood socioeconomic conditions can potentially have effects lasting well beyond the childhood phase.
Project description:This study demonstrates body mass in middle and late adulthood as a consequence of the complex interplay among individuals' genes, lifetime socioeconomic experiences, and the historical context in which they live. Drawing on approximately 9,000 genetic samples from the Health and Retirement Study, we first investigate how socioeconomic status (SES) over the life course moderates the impact of 32 established obesity-related genetic variants on body mass index (BMI) in middle and late adulthood. Further, we consider differences across birth cohorts in the genetic influence on BMI and cohort variations in the moderating effects of life-course SES on the genetic influence. Our analyses suggest that persistently low SES over the life course or downward mobility (e.g., high SES in childhood but low SES in adulthood) amplified the genetic influence on BMI, while persistently high SES or upward mobility (e.g., low SES in childhood but high SES in adulthood) compensated for such influence. For more recent birth cohorts, while the genetic influence on BMI became stronger, the moderating effects of lifetime SES on the genetic influence were weaker compared to earlier cohorts. We discuss these findings in light of social changes during the obesity epidemic in the United States.
Project description:Childhood socioeconomic disadvantage has been previously linked to increased mortality risk in adulthood. However, most previous studies have focused on middle-aged adults in Western contexts. Here, we sought to examine the association between childhood socioeconomic status (SES) and mortality among healthy older Japanese adults.We conducted a 3-year follow-up of participants in the Japan Gerontological Evaluation Study (JAGES), a population-based cohort of 65- to 103-year-old Japanese adults. Childhood SES was assessed by survey at baseline. Mortality from 2010 to 2013 was analysed for 15 449 respondents (7143 men and 8306 women). Cox regression models were used to estimate hazard ratios (HR) for risk of death.A total of 754 deaths occurred during the 3-year follow-up. Lower childhood SES was significantly associated with lower mortality in men, but not in women. Compared with men growing up in more advantaged childhood socioeconomic circumstances, the age-adjusted HR for men from low childhood SES backgrounds was 0.75 [95% confidence interval (CI): 0.56-1.00]. The association remained significant after adjustment for height, education, adult SES, municipalities of residence, health behaviours, disease status and current social relationships (HR?=?0.64; 95% CI 0.47-0.87). This association was stronger among men aged 75 years or older, HR?=?0.67 (95% CI: 0.47-0.95), compared with men aged 65-74 years, HR?=?0.90 (95% CI: 0.54-1.51).Childhood socioeconomic disadvantage is associated with lower mortality among men aged 75 years or older, which may be due to selective survival, or alternatively to childhood physical training or postwar calorie restriction in this generation of Japanese males.
Project description:Childhood socioeconomic status (SES) is inversely associated with adult weight in high income countries. Whether the influence of childhood SES on adult weight is best described using a critical period model or an accumulation of risk model is not yet settled. This research tests whether childhood SES is associated with adult BMI and likelihood of obesity independent of adult socioeconomic status and neighborhood characteristics. Data on individual childhood and adult characteristics come from the Health and Retirement Study (N = 13,545). Data on neighborhood characteristics come from the 2000 Decennial Census and American Community Survey (2005-2009). In the fully adjusted models, perceived financial hardship before the age of sixteen and having a father who was unemployed are associated with higher BMI among males and, among females, paternal education remains associated with adult BMI. However, childhood SES is not associated with likelihood of obesity after fully adjusting for adult SES and neighborhood characteristics, suggesting that the direct effects of early childhood SES on BMI are small relative to the other factors associated with obesity in adulthood.