Modeling Environment Through a General Exposome Factor in Two Independent Adolescent Cohorts


 Exposures to perinatal, familial, social, and physical environmental stimuli can have substantial effects on human development. We aimed to generate a single measure that capture’s the complex network structure of the environment (i.e., exposome) using multi-level data (participant’s report, parent report and geocoded measures) of environmental exposures (primarily from the psychosocial environment) in two independent adolescent cohorts: The Adolescent Brain Cognitive Development Study (ABCD Study, N = 11,235, mean age 10.9 years, 47.7% females) and an age- and sex-matched sample from the Philadelphia Neurodevelopmental Cohort (PNC, N = 4,993). We conducted a series of data-driven iterative factor analyses and bifactor modeling in the ABCD Study, reducing dimensionality from 348 variables tapping to environment to six orthogonal exposome subfactors and a general (adverse) exposome factor. The general exposome factor was associated with overall psychopathology (B = 0.28, 95%CI 0.26-0.3) and key health-related outcomes: obesity (OR = 1.4, 95%CI 1.3-1.5) and advanced pubertal development (OR = 1.3, 95%CI 1.2-1.5). A similar approach in PNC reduced dimensionality of environment from 29 variables to four exposome subfactors and a general exposome factor. PNC analyses yielded consistent associations of the general exposome factor with psychopathology (B = 0.15, 95%CI 0.13-0.17), obesity (OR = 1.4, 95%CI 1.3-1.6) and advanced pubertal development (OR = 1.3, 95%CI 1-1.6). In both cohorts, inclusion of exposome factors greatly increased variance explained in overall psychopathology compared to models relying solely on demographics and parental education (from <4% to > 38% in ABCD; from <4% to > 18.5% in PNC). Findings suggest that a general exposome factor capturing multi-level environmental exposures can be derived and can consistently explain variance in youth’s mental and general health.