Abstract
Background: Nicotine exposure can affect the epigenome of germ cells but little is known about routes of transmission or functional relevance in offspring Aim: To investigate associations between fathers´smoking and changes in offspring DNA methylation, and explore biological impact of methylated loci and annotated genes. Methods: DNA methylation (DNAm) of participants from multigenerational databases (Bergen centre ECRHS/RHINESSA n=98/95) was quantified in whole blood using the Illumina Infinium MethylationEPIC BeadChip. Robust multivariate linear model was used with offspring DNAm as outcome and paternal smoking as exposure, including relevant covariates (offspring/maternal smoking) and cell type proportion. ToppGene and topKEGG was used for pathway analysis. Results: Ever-smoking prevalence was 54% in offspring (mean age 31.3 years) and 42.1% in fathers. At False Discovery Rate (FDR) Conclusion: Fathers´smoking was associated with differential methylation in their children, in particular located to genes involved in Tobacco Use Disorder and ADHD, suggesting an epigenetic contribution and a paternal role in addiction susceptibility and behavioral dysfuntion. (Funding EU Grant 633212, HV)
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