The Early Life Course of Body Weight and Gene Expression Signatures for Disease

Abstract

This study examines how body weight patterns through the first four decades of life relate to gene expression signatures of common forms of morbidity, including cardiovascular diseases (CVD), type 2 diabetes (T2D), and inflammation. As part of Wave V of the nationally representative National Longitudinal Study of Adolescent to Adult Health (1997-2018) in the United States, mRNA abundance data were collected from peripheral blood (n = 1,132). We use a Bayesian modeling strategy to examine the relative associations between body size at five life stages—birth, adolescence, early adulthood, young adulthood, and adulthood—and gene expression-based disease signatures. We compare life course models that consider critical or sensitive periods, as well as accumulation over the entire period. Our results are consistent with a sensitive period model when examining CVD and T2D gene expression signatures: birth weight has a prominent role for the CVD and T2D signatures (explaining 33.1 % and 22.1 %, respectively, of the total association accounted for by body size), while the most recent adult obesity status (age 33–39) is important for both of these gene expression signatures (24.3 % and 35.1%, respectively). Body size in all life stages was associated with inflammation, consistent with the accumulation model.