DNA Methylation as a Mediator of the Association Between Cognitive Ability and Neighborhood Air Pollution in the Fragile Families and Child Wellbeing Study

Abstract

Exposure to environmental pollutants, especially air pollutants, has been associated with adverse development to humans early in life. Current research suggests that the genetic mechanisms controlling neurological function may be negatively impacted upon exposure to air pollution. However, these studies have been limited by sample size, number of pollutants studied, and timing of the exposure examined. To address these concerns, this study analyzed the cumulative effects of 178 pollutants on participants from a large longitudinal cohort study. The purpose of this study is to assess the mediating role of an epigenetic modification, specifically toxin-induced DNA methylation changes, in the association between cognitive ability and children’s exposure to airborne toxins in large cities in the United States. We find that children who grow up in neighborhoods with higher levels of neurologically hazardous air pollution score lower on measures of academic and intellectual ability at age 9 and have significantly accelerated methylation ages, a calculation of “cellular aging”. Additionally, we identify two differentially methylated regions in the promoters of HOXA4 and MGRN1, in the association between cognitive ability and cumulative neurological pollution exposure. Exploring DNA methylation as a mediator of the association between air pollution exposure and lower cognitive ability may establish a more direct link and thus provide insight into the biological mechanisms involved in the effects of environmental toxins on changes in the central nervous system.