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However, there is currently a lack of research addressing the molecular impact of PCE, that may help to clarify the association between PCE and neurodevelopment. To address this knowledge gap, here we present epigenome-wide association study data across multiple time points, examining the effect of PCE and co-exposure with tobacco using two longitudinal studies, the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Christchurch Health and Development Study (CHDS) at birth (0\u2009y), 7\u2009y and 15\u201317\u2009y (ALSPAC), and ~27\u2009y (CHDS). Our findings reveal genome-wide significant DNA methylation differences in offspring at 0\u2009y, 7\u2009y, 15\u201317\u2009y, and 27\u2009y associated with PCE alone, and co-exposure with tobacco. Importantly, we identified significantly differentially methylated CpG sites within the genes <jats:italic>LZTS2, NPSR1, NT5E<\/jats:italic>, <jats:italic>CRIP2, DOCK8, COQ5<\/jats:italic>, and <jats:italic>LRP5<\/jats:italic> that are shared between different time points throughout development in offspring. Notably, functional pathway analysis showed enrichment for differential DNA methylation in neurodevelopment, neurotransmission, and neuronal structure pathways, and this was consistent across all timepoints in both cohorts. Given the increasing volume of epidemiological evidence that suggests a link between PCE and adverse neurodevelopmental outcomes in exposed offspring, this work highlights the need for further investigation into PCE, particularly in larger cohorts.<\/jats:p>","DOI":"10.1038\/s41380-024-02752-w","type":"journal-article","created":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T16:02:01Z","timestamp":1726329721000},"page":"1418-1429","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Prenatal cannabis exposure is associated with alterations in offspring DNA methylation at genes involved in neurodevelopment, across the life course"],"prefix":"10.1038","volume":"30","author":[{"given":"Alexandra J.","family":"Noble","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex T.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Satsangi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1502-1608","authenticated-orcid":false,"given":"Joseph M.","family":"Boden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4943-3486","authenticated-orcid":false,"given":"Amy J.","family":"Osborne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,14]]},"reference":[{"key":"2752_CR1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ntt.2018.06.001","volume":"68","author":"VH Coleman-Cowger","year":"2018","unstructured":"Coleman-Cowger VH, Oga EA, Peters EN, Mark K. 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