RESUMO
Population-level analyses are inherently complex due to a myriad of latent confounding effects that underlie the interdisciplinary topics of research interest. Despite the mounting demand for generative population models, the limited generalizability to underrepresented groups hinders their widespread adoption in downstream applications. Interpretability and reliability are essential for clinicians and policymakers, while accuracy and precision are prioritized from an engineering standpoint. Thus, in domains such as population neuroscience, the challenge lies in determining a suitable approach to model population data effectively. Notably, the traditional strata-agnostic nature of existing methods in this field reveals a pertinent gap in quantitative techniques that directly capture major sources of population stratification. The emergence of population-scale cohorts, like the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study, provides unparalleled opportunities to explore and characterize neurobehavioral and sociodemographic relationships comprehensively. We propose diversity-aware population modeling, a framework poised to standardize systematic incorporation of diverse attributes, structured with respect to intrinsic population stratification to obtain holistic insights. Here, we leverage Bayesian multilevel regression and poststratification, to elucidate inter-individual differences in the relationships between socioeconomic status (SES) and cognitive development. We constructed 14 varying-intercepts and varying-slopes models to investigate 3 cognitive phenotypes and 5 sociodemographic variables (SDV), across 17 US states and 5 race subgroups. SDVs exhibited systemic socio-spatial effects that served as fundamental drivers of variation in cognitive outcomes. Low SES was disproportionately associated with cognitive development among Black and Hispanic children, while high SES was a robust predictor of cognitive development only among White and Asian children, consistent with the minorities' diminished returns (MDRs) theory. Notably, adversity-susceptible subgroups demonstrated an expressive association with fluid cognition compared to crystallized cognition. Poststratification proved effective in correcting group attribution biases, particularly in Pennsylvania, highlighting sampling discrepancies in US states with the highest percentage of marginalized participants in the ABCD Study©. Our collective analyses underscore the inextricable link between race and geographic location within the US. We emphasize the importance of diversity-aware population models that consider the intersectional composition of society to derive precise and interpretable insights across applicable domains.
RESUMO
Our genetic makeup, together with environmental and social influences, shape our brain's development. Yet, the imaging genetics field has struggled to integrate all these modalities to investigate the interplay between genetic blueprint, environment, human health, daily living skills and outcomes. Hence, we interrogated the Adolescent Brain Cognitive Development (ABCD) cohort to outline the effects of rare high-effect genetic variants on brain architecture and corresponding implications on cognitive, behavioral, psychosocial, and socioeconomic traits. Specifically, we designed a holistic pattern-learning algorithm that quantitatively dissects the impacts of copy number variations (CNVs) on brain structure and 962 behavioral variables spanning 20 categories in 7,657 adolescents. Our results reveal associations between genetic alterations, higher-order brain networks, and specific parameters of the family well-being (increased parental and child stress, anxiety and depression) or neighborhood dynamics (decreased safety); effects extending beyond the impairment of cognitive ability or language capacity, dominantly reported in the CNV literature. Our investigation thus spotlights a far-reaching interplay between genetic variation and subjective life quality in adolescents and their families.