Abstract: Genome-wide association studies with transcript abundance in peripheral blood samples or derivative cell lines have demonstrated a preponderance of regulatory polymorphisms, also known as eSNPs, which impact the expression of several percent of all genes. Several of these highlight associations that contribute to a variety of disease conditions, but the question arises as to how the associations are affected by the environment. We have addressed the robustness of eSNP associations to decanalization of the transcriptome in the face of different biotic and abiotic challenges faced in different geographic locations. I will describe a gene expression GWAS that controls for population structure and lifestyle, in a comparison of Arab and Amazigh individuals from a city and two villages in southern Morocco. Approximately 400 genomewide significant associations are observed in leukocyte samples obtained from 194 individuals, the vast majority in cis, and all are consistent across the three sample locations and after controlling for ethnicity and relatedness, despite substantial divergence in the structure of the transcriptome in rural villagers. No evidence for large-effect trans-acting mediators of the pervasive environmental influence is found and instead genetic and environmental factors appear to act in a largely additive manner. I will discuss the implications for the origins of complex disease in human societies undergoing profound transitions where genotype-by-environment interactions might be expected to influence disease risk.