A Genome-Wide Gene Expression Signature of Environmental Geography in Leukocytes of Moroccan Amazighs

Abstract

The different environments that humans experience are likely to impact physiology and disease susceptibility. In order to estimate the magnitude of the impact of environment on transcript abundance, we examined gene expression in peripheral blood leukocyte samples from 46 desert nomadic, mountain agrarian and coastal urban Moroccan Amazigh individuals. Despite great expression heterogeneity in humans, as much as one third of the leukocyte transcriptome was found to be associated with differences among regions. Genome-wide polymorphism analysis indicates that genetic differentiation in the total sample is limited and is unlikely to explain the expression divergence. Methylation profiling of 1,505 CpG sites suggests limited contribution of methylation to the observed differences in gene expression. Genetic network analysis further implies that specific aspects of immune function are strongly affected by regional factors and may influence susceptibility to respiratory and inflammatory disease. Our results show a strong genome-wide gene expression signature of regional population differences that presumably include lifestyle, geography, and biotic factors, implying that these can play at least as great a role as genetic divergence in modulating gene expression variation in humans. The incidence of complex diseases such as diabetes, asthma, and depression is almost epidemic in many countries and coincides with transition in lifestyles. Clearly this is a result of interaction between modern cultural and environmental factors with the genetic legacy of human history. To estimate the extent of the effects of environmental factors, including lifestyle and geography, on gene expression, we examined gene expression differentiation in peripheral blood leukocyte samples from three Moroccan Amazigh groups leading distinct ways of life: desert nomadic, mountain agrarian and coastal urban. Our data shows that as much as one third of the leukocyte transcriptome is associated with differences among the three regions. Network analysis implies that specific aspects of immune function are strongly affected by regional factors and may influence disease susceptibility. Genetic and methylation differentiation between the three regions is limited and is unlikely to explain the extent of the observed gene expression differentiation. Insight gained from this study highlights the impact transitions from traditional to modern lifestyles likely have on human disease susceptibility and further warrant the need to incorporate gene expression profiling alongside genetic association studies for the prediction of disease susceptibility.