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

Laurel Raffington; Lisa Schneper; Travis Mallard; Jonah Fisher; Liza Vinnik; Kelseanna Hollis-Hansen; Daniel A Notterman; Elliot M Tucker-Drob; Colter Mitchell; Kathryn P Harden

doi:10.1101/2023.01.20.524709

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

bioRxiv [Preprint]. 2023 Jan 20:2023.01.20.524709. doi: 10.1101/2023.01.20.524709.

Authors

Laurel Raffington^{1

2}, Lisa Schneper³, Travis Mallard^{2

4

5}, Jonah Fisher⁶, Liza Vinnik², Kelseanna Hollis-Hansen⁷, Daniel A Notterman³, Elliot M Tucker-Drob², Colter Mitchell^{4

8}, Kathryn P Harden²

Affiliations

¹ Max Planck Institute for Human Development, Max Planck Research Group Biosocial - Biology, Social Disparities, and Development, Lentzeallee 94, 14195 Berlin, Germany.
² Population Research Center, The University of Texas at Austin, Austin, TX, USA.
³ Department of Molecular Biology, Princeton University, Princeton, NJ.
⁴ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁵ Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
⁶ Survey Research Center, University of Michigan, Ann Arbor, MI.
⁷ Peter O'Donnell Jr. School of Public Health, UT Southwestern Medical Center, Dallas, TX.
⁸ Population Studies Center, University of Michigan, Ann Arbor, MI.

Abstract

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.

Keywords: DNA methylation; aging; body mass index; epigenetics; social determinants of health.

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