Tobacco smoke has been shown to cause highly reproducible changes to the methylome. This has been observed in response to own smoking but also in offspring exposed to maternal smoking in utero. Sustained maternal smoking during pregnancy is associated with aberrant DNA methylation reported in large-scale epigenome-wide association studies (EWAS) of cord blood (1,2). Associations are also seen with paternal smoking, although these largely attenuate when adjusted for maternal smoking (explained by the correlation of maternal and paternal smoking habits). However, all the EWAS for prenatal smoking exposure performed in cord blood to date have focused on autosomes and sex chromosomes have been previously excluded from the analysis. We propose that methylation changes induced in sex chromosomes may have biological importance and we seek to specifically analyse these in the Accessible Resource for Integrated Epigenomic Studies (ARIES).
We hypothesise that paternal and maternal exposure to cigarette smoke may lead to DNA methylation variation in the offspring sex chromosomes and these aberrations may increase the susceptibility of exposed offspring to adverse perinatal outcomes.

References:
1. Joubert BR, Felix JF, Yousefi P, Bakulski KM, Just AC, Breton C, et al. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis. Am J Hum Genet 2016;98(4):680-96.
2. Richmond RC, Simpkin AJ, Woodward G, Gaunt TR, Lyttleton O, McArdle WL, et al. Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC). Hum Mol Genet 2015;24(8):2201-17.