Epigenetic Pathways of Socioeconomic Disparities in Physical and Cognitive Health Across the Lifespan

Project Summary Children who grow up in low-income homes are at risk for worse physical and cognitive health for their entire lives, a phenomenon known as the “long arm of childhood”. But, understanding and intervening on this process is enormously difficult, as the effects of childhood environments can take decades to become visible in adult

morbidity and mortality. What researchers need is a “wormhole”, i.e., a passage through time that connects childhood and adulthood. In the proposed research, we will examine the utility of DNA-methylation (DNAm) as a “molecular wormhole” for investigating how material and social conditions of childhood are linked with

physical and cognitive health across the lifespan. We have exciting preliminary research that supports our key hypothesis that methylation profile scores (MPSs) can allow researchers to “see” – in real time – the impact of children’s social environments on their lifelong risk for poor cognitive and physical health. However, there

remain yawning gaps in knowledge about the utility (and limitations) of MPSs for studying the life course. First, MPSs have yet to be integrated into experimental, longitudinal designs capable of testing causal hypotheses about the impact of childhood environments on development. Building on the Baby’s First Years Study (BFY;

est. N=850), we will, for the first time, integrate MPSs into a randomized controlled trial testing whether unconditional cash transfers to low-income mothers for the first ~6-years of the child’s life cause changes in the child’s methylome in early childhood. Next, we will examine whether MPSs show potential for change early in

the life course and whether this change is associated with longitudinal development of cognitive and physical health across childhood in the BFY (ages 4 and 6), Texas Twin Project (TTP, N=1404, ages 8-20), and Future of Families and Child Well-Being Study (FFCWS, N = 2,020, ages 9 and 15). Second, previous studies testing

DNAm as a molecular wormhole have only traveled one way, by applying MPSs developed in studies of adult health in child samples. We will travel forward through the wormhole, by developing MPSs that index the socioeconomic conditions of childhood (comparing children in BFY low vs. high-cash groups, and in low vs.

high SES families in TTP and FFCWS), and testing their associations with longitudinal development of cognitive and physical health in early childhood to adolescence and in older adulthood (Health and Retirement Study, N = 4,018). Finally, in order to derive candidate biological mechanisms of action, research must

augment summary MPS measures with informatic approaches that identify biological pathways. We will delineate overlapping and diverging biological pathways implicated in genomic markers identified in analyses of socioeconomic contexts and cash gifts in childhood and markers identified in published adult studies of

health. This application is poised to make rapid scientific progress as all measures, including biological specimens, are either already available or already being collected as part of separately funded projects.