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

Abstract

ImportanceChildren 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresSocioeconomic status, marginalized groups.Main Outcome and MeasureSalivary 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.ResultsSalivary 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 RelevanceThis 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.

Linked emergence of racial disparities in mental health and epigenetic biological aging across childhood and adolescence

“…Additionally, Black compared to White identifying children, children living in more racially segregated neighborhoods, and marginalized children with darker skin tones, tended to have higher age-9 levels of biological aging and more biological age acceleration over adolescence. This is in line with previous cross-sectional findings in children and adults (Martz et al, 2024; Mitchell et al, 2016; Raffington, Schneper, et al, 2023b; Shen et al, 2023). For example, Hicken and colleagues (2023) find that Black compared to White identifying adults have higher GrimAge and PhenoAge Acceleration (GrimAge Acceleration: b = .42, 95% CI .20 to .64, p <.001; PhenoAge Acceleration: b = .29, 95% CI .02 to .57, p <.001).…”

“…Next, we tested for racial and ethnic disparities in saliva DNAm quantifications of biological aging (DunedinPACE, GrimAge Acceleration, PhenoAge Acceleration), combining repeated DNAm measures from ages 9 and 15 in univariate latent change score models. While these DNAm measures of biological aging were developed in blood (Belsky et al, 2022; Levine et al, 2018; Lu et al, 2019), our previous findings suggest good cross-tissue correspondence to saliva DNAm residualized for cell composition, presumably because of the high immune cell signal in both blood and saliva (Middleton et al, 2022; Raffington, Schneper, et al, 2023a; Raffington, Tanksley, et al, 2023).…”

“…Racial marginalization and low socioeconomic status has been associated with more advanced and faster biological aging as measured in DNAm in both adults and children, and, in adults, these differences in biological aging partially account for health disparities between and within racial groups (Del Toro et al, 2022; Oblak et al, 2021; Raffington et al, 2021; Sugden et al, 2023). A few studies have found DNAm measures of biological aging to be associated with mental health (Cecil et al, 2023; Oblak et al, 2021; Raffington, Tanksley, et al, 2023). Yet, previous research has largely been cross-sectional in design and, thus, does not address the dynamic interplay between racialization, mental health, and biological aging.…”

Stability of DNA-Methylation Profiles of Biological Aging in Children and Adolescents

“…61 Furthermore, other salivary MPSs (for BMI and epigenetic age) have demonstrated strong longitudinal stability in adolescence. 24,25 Together these results suggest that the relative instability of aging-related MPSs observed in the current study is not an artifact of salivary DNAm measurement. Nevertheless, as saliva is more feasible to collect in large pediatric cohorts than blood, future research on how aging-related biology changes in early life will benefit from the development of MPSs specifically trained on salivary data.…”

“…Previous work on telomere length has found evidence for high rank-order stability already in childhood (measured at age 11 and 14-year follow-up). 23 Similarly, some saliva-based MPSs have been found to be fairly stable in adolescence: a salivary MPS of BMI showed a test-retest correlation of 0.63 from age 9 to 15, 24 while Horvath epigenetic age measured in saliva showed a 2-year test-retest stability of r = 0.73 in early adolescence (mean age at baseline = 12.5 years). 25 Whether other salivary MPSs show more longitudinal instability in childhood and adolescence is unknown, and this information can provide valuable context for understanding when aging-related biology might be most sensitive to environmental intervention.…”