Using a DNA-methylation smoking score to assess the association between maternal smoking during pregnancy and neurodevelopmental disorder in childhood.

Summary
Maternal smoking during pregnancy has been related to lower child neurodevelopment and higher behavioural problems. This project will assess the relationship between maternal smoking, using a DNA-methylated score during pregnancy on various aspect of child cognitive and behavioural development.

Background and rationale
Researchers now recognize that many of the mechanisms whereby maternal smoke exposure may affect key pathways crucial for proper brain development are epigenetically based {Knopik, 2012 #30}. Indeed, Cigarette smoke is a potent environmental modifier of DNA methylation {Wiklund, 2019 #92}{Joelsson, 2016 #91}. Therefore, a possible mechanism by which early-life environmental exposures such as maternal smoking influence the onset of neurodevelopmental onset later in life has been proposed to act through epigenetic changes via altered DNA methylation and microRNA expression{ndre Sourander, #95} j{Jirtle, 2007 #1}{Lan Huang, #94}{Joubert, 2016 #97}. The harmonization of mental health problems in several population-based birth cohorts will allow us to perform trajectory analyses with specific mental health domains.

Overall, in this study, we will study the association of a machine learning-based DNA-methylation smoking score during pregnancy for fetal exposure to maternal smoking during pregnancy and the trajectories of childhood neurodevelopment (outcomes include internalisation and externalisation, autism and ADHD) at different ages.

This study will use harmonized data (by mapping individual instruments, domain types and age groups) from various large birth cohorts across Europe and Australia.