Modeling environment through a general exposome factor in two independent adolescent cohorts

Abstract

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.

Allostatic load in early adolescence: gene / environment contributions and relevance for mental health

“…92 Adoption of the exposome framework has allowed us to quantify exposomic burden in a single measure. 49 Here, we combine these tools and show not only additive polygenic and exposomic effects on AL in early adolescence, but also significant G X E interaction. This finding adds to the literature suggesting that genetic effects on youth health outcomes vary by environment.…”

“…Based on the conceptualization that AL is driven by cumulative stress exposure, we tested the longitudinal association of overall childhood exposomic burden, modeled using a single overall adverse exposome calculated at age 11 49 with AL in the diverse study sample (N=5,035, see Table 1 for detailed demographic characteristics). Exposomic burden was significantly associated with AL a year later (beta=0.25, 95%CI 0.22-0.29, P<.001; Figure 3A ).…”

“…This measure was calculated following dimensionality reduction of 348 environmental variables collected by the second ABCD assessment wave, as we previously described. 49 Briefly, we conducted iterative exploratory factor analyses on environmental measures and identified six domains of environment 54 ( household adversity factor, neighborhood environment factor, day-to-day experiences factor, state environment factor, family values factor, and pregnancy/birth complications factor). Thereafter, we estimated a bifactor model 55 that generated a general adverse exposome factor and six orthogonal subfactors.…”

“…46,47 Notably, gene-environment studies are complicated due to the large genotyped sample sizes needed for adequate power and the methodological challenge of measuring environmental exposures (i.e., exposome). Converging advances in (i) statistical genetics that enable the use of generalizable polygenic risk models 48 ; (ii) statistical methods that quantify aggregate environmental burden, 49 and (iii) the availability of large-scale data of genotyped youth cohorts with detailed phenotypic measures, create opportunities to unravel genetic and exposomic mechanisms in the development of AL. 50 Here, we leverage multimodal data on thousands of genotyped youths from the Adolescent Brain Cognitive Development SM Study (ABCD Study®) who were followed from late childhood into early adolescence.…”

Multilayer network associations between the exposome and childhood brain development

“…The exposome, defined as the totality of environmental exposures across the lifespan, was originally established to address the need for more comprehensive evaluation of environmental exposures in relation to epidemiological outcomes (Wild, 2012). Since then, psychiatry studies have investigated the exposome’s role in relation to psychopathological outcomes using factor analysis, which reduces multiple exposures to a few factors (e.g., Barzilay et al, 2021; Guloksuz et al, 2018; Moore et al, 2022; Pries et al, 2022; Sydnor et al, 2023). However, this approach alone might not be able to fully capture the complexity of relationships between environmental exposures and outcomes of interest.…”