Hypomethylation in FASTKD1 detected in the association between in utero tobacco exposure and conduct problem in a New Zealand longitudinal study

Abstract Despite the known adverse effects of in utero tobacco exposure on offspring health, maternal tobacco use during pregnancy remains prevalent and is a major driver of health inequalities. One such health inequality is the development of conduct problem (CP) in exposed offspring which may be mediated by methylation changes that persist into adulthood. Here we apply a genome-wide approach to probe the association between maternal tobacco use during pregnancy and CP outcomes in exposed offspring. We examined maternal tobacco use during pregnancy ( in utero exposure) in the Christchurch Health and Development Study, a longitudinal birth cohort studied for over 40 years. We then evaluated the interaction between methylation effects of in utero exposure and CP score. When modelling this interaction between in utero exposure and CP score we detected nominal DNA methylation differences, at FASTKD1 which has roles in early development. Our observations are consistent with DNA methylation mediating the development of CP following in utero tobacco exposure. In addition, we detected nominal significance in FRMDA4 and MYO1G between individuals exposed to tobacco in utero and those that were unexposed, however these did not reach significance after adjustment for multiple testing. However due to limited power in our analysis, further studies are needed to investigate the interaction between in utero tobacco exposure and high CP health outcomes.