Reducing the complexity of high-dimensional environmental data: An analytical framework using LASSO with considerations of confounding for statistical inference

Purpose: Frameworks for selecting exposures in high-dimensional environmental datasets, while considering confounding, are lacking. We present a two-step approach for exposure selection with subsequent confounder adjustment for statistical inference. Methods: We measured cognitive ability in 338 children using the Woodcock-Muñoz General Intellectual Ability (GIA) score, and potential associated features across several environmental domains. Initially, 111 variables theoretically associated with GIA score were introduced into a Least Absolute Shrinkage and Selection Operator (LASSO) in a 50% feature selection subsample. Effect estimates for selected features were subsequently modeled in linear regressions in a 50% inference (hold out) subsample, first adjusting for sex and age and later for covariates selected via directed acyclic graphs (DAGs). All models were adjusted for clustering by school. Results: Of the 15 LASSO selected variables, eleven were not associated with GIA score following our inference modeling approach. Four variables were associated with GIA scores, including: serum ferritin adjusted for inflammation (inversely), mother's IQ (positively), father's education (positively), and hours per day the child works on homework (positively). Serum ferritin was not in the expected direction. Conclusions: Our two-step approach moves high-dimensional feature selection a step further by incorporating DAG-based confounder adjustment for statistical inference.