DNA methylation analysis using bisulphite-based amplicon sequencing of individuals exposed to maternal tobacco use during pregnancy, and offspring conduct problems in childhood and adolescence

Abstract

Maternal tobacco smoking during pregnancy is a large driver of health inequalities and a higher prevalence of conduct problem (CP) has been observed in exposed offspring. Further, maternal tobacco use during pregnancy can also alter offspring DNA methylation. However, currently, limited molecular evidence has been found to support this observation. Thus we aim to examine the association between maternal tobacco use in pregnancy and offspring CP, to determine whether offspring CP is mediated by tobacco exposure-induced DNA methylation differences. Understanding the etiology of the association between maternal tobacco use and offspring CP will be crucial in the early identification and treatment of CP in children and adolescents. Here, a sub group of N = 96 individuals was sourced from the Christchurch Health and Development Study, a longitudinal birth cohort studied for over 40 years in New Zealand. Whole blood samples underwent bisulphite-based amplicon sequencing at 10 loci known to play a role in neurodevelopment, or which had associations with CP phenotypes. We identified significant (P < 0.05) differential DNA methylation at specific CpG sites in CYP1A1, ASH2L and MEF2C in individuals with CP who were exposed to tobacco in utero. We conclude that environmentally-induced DNA methylation differences could play a role in the observed link between maternal tobacco use during pregnancy and childhood/adolescent CP. However, larger sample sizes are needed to produce an adequate amount of power to investigate this interaction further.