Prenatal cannabis exposure (PCE) is of increasing concern globally, due to the potential impact on offspring neurodevelopment, and its association with childhood and adolescent brain development and cognitive function. 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 y), 7 y and 15–17 y (ALSPAC), and ~27 y (CHDS). Our findings reveal genome-wide significant DNA methylation differences in offspring at 0 y, 7 y, 15–17 y, and 27 y associated with PCE alone, and co-exposure with tobacco. Importantly, we identified significantly differentially methylated CpG sites within the genes LZTS2, NPSR1, NT5E, CRIP2, DOCK8, COQ5, and LRP5 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.

产前大麻暴露 （PCE） 在全球范围内越来越受到关注，因为它对后代神经发育的潜在影响，以及它与儿童和青少年大脑发育和认知功能的关联。然而，目前缺乏解决 PCE 分子影响的研究，这可能有助于阐明 PCE 与神经发育之间的关联。为了解决这一知识差距，我们在这里提供了跨多个时间点的表观基因组范围关联研究数据，使用两项纵向研究，即雅芳父母和儿童纵向研究 （ALSPAC） 和基督城健康与发展研究 （CHDS） 在出生时 （0 y）、7 y 和 15-17 y （ALSPAC）， 和 ~27 y （CHDS）。我们的研究结果揭示了后代在 0 年、7 年、15-17 年和 27 年时全基因组显着的 DNA 甲基化差异，这些差异与单独 PCE 以及与烟草的共同暴露有关。重要的是，我们在基因 LZTS2 、 NPSR1 、 NT5E 、 CRIP2 、 DOCK8 、 COQ5 和 LRP5 中鉴定了显著差异化的 CpG 位点，这些位点在整个子代发育过程中的不同时间点之间共享。值得注意的是，功能通路分析显示神经发育、神经传递和神经元结构通路中差异 DNA 甲基化的富集，这在两个队列的所有时间点都是一致的。鉴于越来越多的流行病学证据表明 PCE 与暴露后代的不良神经发育结果之间存在联系，这项工作强调了进一步调查 PCE 的必要性，尤其是在较大的队列中。