Compositional Outcomes and Environmental Mixtures: the Dirichlet Bayesian Weighted Quantile Sum Regression

Abstract: Environmental mixture approaches do not accommodate compositional outcomes, consisting of vectors constrained onto the unit simplex. This limitation poses challenges in effectively evaluating the associations between multiple concurrent environmental exposures and their respective impacts on this type of outcomes. As a result, there is a pressing need for the development of analytical methods that can more accurately assess the complexity of these relationships. Here, we extend the Bayesian weighted quantile sum regression (BWQS) framework for jointly modeling compositional outcomes and environmental mixtures using a Dirichlet distribution with a multinomial logit link function. The proposed approach, named Dirichlet-BWQS (DBWQS), allows for the simultaneous estimation of mixture weights associated with each exposure mixture component as well as the association between the overall exposure mixture index and each outcome proportion. We assess the performance of DBWQS regression on extensive simulated data and a real scenario where we investigate the associations between environmental chemical mixtures and DNA methylation-derived placental cell composition, using publicly available data (GSE75248). We also compare our findings with results considering environmental mixtures and each outcome component. Finally, we developed an R package "xbwqs" where we made our proposed method publicly available (https://github.com/hasdk/xbwqs).