ИСТИНА

Background: Family social factors affect the life-course of offspring, particularly until young adulthood. We investigated the association of parental education and family income with subsequent human sperm DNA methylation. Design and Methods: The Russian Children’s Study is a prospective cohort of 516 boys who were enrolled at 8-9 years of age, completed family’s detailed questionnaire and provided semen samples at 18-19 years. Maximum parental education was dichotomized as high or low, for family income we used cut-off as 5000 rub/month at enrollment stage. RRBS of 34 sperm samples from fractionated ejaculates was conducted using HiSeq2000. DMRcate was used to identify differentially methylated regions (DMR) in multivariate regression analysis followed by enrichment analyses by Metascape. Main Results: 14 (41%) families had higher education, while 9 (27%) had an income less than 5000 rub/month. In multivariate regression models adjusted for peripubertal exposure to dioxins and lead, birthweight, subject’s BMI, smoking, analytical batch and semen quality we found 62 and 58 DMRs for parental education and baseline family income, respectively. Ontology analyses revealed that mitotic prometaphase and microtubule-based processes were top scoring networks for parental education and regulation of macroautophagy for family income. Conclusions: Findings from our prospective study suggest that social determinants are associated with sperm DNA methylation in young adults. Funding: Epigenetic part of study was supported by Russian Science Foundation (RSF) [grant numbers 14-45-00065 and 18-15-00202]; parent RCS was supported by US EPA [grant number R82943701] and by NIEHS [grant number R01 ES014370].