Salivary Epigenetic Measures of Body Mass Index and Social Determinants of Health Across Childhood and Adolescence.

Importance: Children who are socioeconomically disadvantaged are at increased risk for high body mass index (BMI) and multiple diseases in adulthood. The developmental origins of health and disease hypothesis proposes that early life conditions affect later-life health in a manner that is only partially modifiable by later-life experiences. Objective: To examine whether epigenetic measures of BMI developed in adults are valid biomarkers of childhood BMI and if they are sensitive to early life social determinants of health. Design, Setting, and Participants: This population-based study of over 3200 children and adolescents aged 8 to 18 years included data from 2 demographically diverse US pediatric cohort studies that combine longitudinal and twin study designs. Analyses were conducted from 2021 to 2022. Exposures: Socioeconomic status, marginalized groups. Main Outcome and Measure: Salivary epigenetic BMI, BMI. Analyses were conducted to validate the use of saliva epigenetic BMI as a potential biomarker of child BMI and to examine associations between epigenetic BMI and social determinants of health. Results: Salivary epigenetic BMI was calculated from 2 cohorts: (1) 1183 individuals aged 8 to 18 years (609 female [51%]; mean age, 13.4 years) from the Texas Twin Project and (2) 2020 children (1011 female [50%]) measured at 9 years of age and 15 years of age from the Future of Families and Child Well-Being Study. Salivary epigenetic BMI was associated with children's BMI (r = 0.36; 95% CI, 0.31-0.40 to r = 0.50; 95% CI, 0.42-0.59). Longitudinal analysis found that epigenetic BMI was highly stable across adolescence but remained both a leading and lagging indicator of BMI change. Twin analyses showed that epigenetic BMI captured differences in BMI between monozygotic twins. Moreover, children from more disadvantaged socioeconomic status (b = -0.13 to -0.15 across samples) and marginalized racial and ethnic groups (b = 0.08-0.34 across samples) had higher epigenetic BMI, even when controlling for concurrent BMI, pubertal development, and tobacco exposure. Socioeconomic status at birth relative to concurrent socioeconomic status best predicted epigenetic BMI in childhood and adolescence (b = -0.15; 95% CI, -0.20 to -0.09). Conclusion and Relevance: This study demonstrated that epigenetic measures of BMI calculated from pediatric saliva samples were valid biomarkers of childhood BMI and may be associated with early-life social inequalities. The findings are in line with the hypothesis that early-life conditions are especially important factors in epigenetic regulation of later-life health. Research showing that health later in life is linked to early-life conditions has important implications for the development of early-life interventions that could significantly extend healthy life span.

Measuring the long arm of childhood in real-time: Epigenetic predictors of BMI and social determinants of health across childhood and adolescence.

Children who are socioeconomically disadvantaged are at increased risk for high body mass index (BMI) and multiple diseases in adulthood. The developmental origins of health and disease hypothesis proposes that early life conditions affect later-life health in a manner that is only partially modifiable by later-life experiences. Epigenetic mechanisms may regulate the influence of early life conditions on later life health. Recent epigenetic studies of adult blood samples have identified DNA-methylation sites associated with higher BMI and worse health (epigenetic-BMI). Here, we used longitudinal and twin study designs to examine whether epigenetic predictors of BMI developed in adults are valid biomarkers of child BMI and are sensitive to early life social determinants of health. Salivary epigenetic-BMI was calculated from two samples: (1) N=1,183 8-to-19-year-olds (609 female, mean age=13.4) from the Texas Twin Project (TTP), and (2) N=2,020 children (1,011 female) measured at 9 and 15 years from the Future of Families and Child Well-Being Study (FFCWS). We found that salivary epigenetic-BMI is robustly associated with children's BMI (r=0.36 to r=0.50). Longitudinal analysis suggested that epigenetic-BMI is highly stable across adolescence, but remains both a leading and lagging indicator of BMI change. Twin analyses showed that epigenetic-BMI captures differences in BMI between monozygotic twins. Moreover, children from more disadvantaged socioeconomic status (SES) and marginalized race/ethnic groups had higher epigenetic-BMI, even when controlling for concurrent BMI, pubertal development, and tobacco exposure. SES at birth relative to concurrent SES best predicted epigenetic-BMI in childhood and adolescence. We show for the first time that epigenetic predictors of BMI calculated from pediatric saliva samples are valid biomarkers of childhood BMI that are sensitive to social inequalities. Our findings are in line with the hypothesis that early life conditions are especially important factors in epigenetic regulation of later life health. Research showing that health later in life is linked to early life conditions have important implications for the development of early-life interventions that could significantly extend healthy life span.

Impact of paternal education on epigenetic ageing in adolescence and mid-adulthood: a multi-cohort study in the USA and Mexico.

BACKGROUND: Both parental and neighbourhood socio-economic status (SES) are linked to poorer health independently of personal SES measures, but the biological mechanisms are unclear. Our objective was to examine these influences via epigenetic age acceleration (EAA)-the discrepancy between chronological and epigenetic ages. METHODS: We examined three USA-based [Coronary Artery Risk Disease in Adults (CARDIA) study, Fragile Families and Child Wellbeing Study (FFCWS) and Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS)] and one Mexico-based (Project Viva) cohort. DNA methylation was measured using Illumina arrays, personal/parental SES by questionnaire and neighbourhood disadvantage from geocoded address. In CARDIA, we examined the most strongly associated personal, parental and neighbourhood SES measures with EAA (Hannum's method) at study years 15 and 20 separately and combined using a generalized estimating equation (GEE) and compared with other EAA measures (Horvath's EAA, PhenoAge and GrimAge calculators, and DunedinPoAm). RESULTS: EAA was associated with paternal education in CARDIA [GEEs: ßsome college = -1.01 years (-1.91, -0.11) and ß

The Longitudinal Associations Between Paternal Incarceration and Family Well-Being: Implications for Ethnic/Racial Disparities in Health.

OBJECTIVE: Ethnic/racial minority children in the United States are more likely to experience father loss to incarceration than White children, and limited research has examined the health implications of these ethnic/racial disparities. Telomere length is a biomarker of chronic stress that is predictive of adverse health outcomes. This study examined whether paternal incarceration predicted telomere length shortening among offspring from childhood to adolescence, whether maternal depression mediated the link, and whether ethnicity/race moderated results. METHOD: Research participants included 2,395 families in the Fragile Families and Child Wellbeing study, a national and longitudinal cohort study of primarily low-income families from 20 large cities in the United States. Key constructs were measured when children were on average ages 9 (2007-2010) and 15 (2014-2017). RESULTS: Children who experienced paternal incarceration exhibited shorter telomere lengths between ages 9 and 15, and changes in maternal depression mediated this finding. Specifically, mothers who experienced a partner's incarceration were more likely to have depression between children's ages 9 and 15. In turn, increases in maternal depression between children's ages 9 and 15 predicted more accelerated telomere length shortening among children during this period. Paternal incarceration was more prevalent and frequent for ethnic/racial minority youth than for White youth. CONCLUSION: Paternal incarceration is associated with a biomarker of chronic stress among children in low-income families. Rates of paternal incarceration were more prevalent and frequent among Black American and multiethnic/multiracial families than among White Americans. As a result, the mass incarceration crisis of the criminal justice system is likely shaping intergenerational ethnic/racial health disparities.

Coming up short: Comparing venous blood, dried blood spots & saliva samples for measuring telomere length in health equity research.

BACKGROUND: Telomere length (TL) in peripheral blood mononuclear cells (PBMC) from fresh venous blood is increasingly used to estimate molecular impacts of accumulated social adversity on population health. Sometimes, TL extracted from saliva or dried blood spots (DBS) are substituted as less invasive and more scalable specimen collection methods; yet, are they interchangeable with fresh blood? Studies find TL is correlated across tissues, but have not addressed the critical question for social epidemiological applications: Do different specimen types show the same association between TL and social constructs? METHODS: We integrate expertise in social epidemiology, molecular biology, and the statistical impact of measurement error on parameter estimates. Recruiting a diverse sample of 132 Metro-Detroit women, we measure TL for each woman from fresh blood PBMC, DBS, and saliva. Using regression methods, we estimate associations between social characteristics and TL, comparing estimates across specimen types for each woman. RESULTS: Associations between TL and social characteristics vary by specimen type collected from the same woman, sometimes qualitatively altering estimates of the magnitude or direction of a theorized relationship. Being Black is associated with shorter TL in PBMC, but longer TL in saliva or DBS. Education is positively associated with TL in fresh blood, but negatively associated with TL using DBS. CONCLUSION: Findings raise concerns about the use of TL measures derived from different tissues in social epidemiological research. Investigators need to consider the possibility that associations between social variables and TL may be systematically related to specimen type, rather than be valid indicators of socially-patterned biopsychosocial processes.