“…One such avenue of untangling GxE from cohort studies is through identifying the interaction between PGS, widely used to define genotype–phenotype relationships, and the exposome. , In a toxicology context, human-induced pluripotent stem cells (iPSCs) represent a new approach methodology (NAM) to reduce animal testing in human toxicology screens (in this case, secondary laboratory testing using iPSCs and the models derived from them (e.g., organoids)). With emerging opportunities to derive primary cells from a range of biosamples (e.g., peripheral blood mononuclear cells relevant to the immune responses, hair keratinocytes, and urine that can subsequently be reprogrammed to differentiate into multiple cell types (e.g., urine-derived iPSCs can be reprogrammed to urinary epithelial cells, endothelial cells, nerve cells, skeletal myogenic cells, osteoblasts, adipocytes, and chondrocytes)), this provides a promising opportunity to test GxE.…”