Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Transl Psychiatry. 2022 Sep 30;12(1):418. doi: 10.1038/s41398-022-02195-3.
Prenatal tobacco exposure (PTE) and prenatal alcohol exposure (PAE) have been associated with an increased risk of delayed neurodevelopment in children as well as differential newborn DNA methylation (DNAm). However, the biological mechanisms connecting PTE and PAE, DNAm, and neurodevelopment are largely unknown. Here we aim to determine whether differential DNAm mediates the association between PTE and PAE and neurodevelopment at 6 (N = 112) and 24 months (N = 184) in children from the South African Drakenstein Child Health Study. PTE and PAE were assessed antenatally using urine cotinine measurements and the ASSIST questionnaire, respectively. Cord blood DNAm was measured using the EPIC and 450 K BeadChips. Neurodevelopment (cognitive, language, motor, adaptive behavior, socioemotional) was measured using the Bayley Scales of Infant and Toddler Development, Third Edition. We constructed methylation risk scores (MRS) for PTE and PAE and conducted causal mediation analysis (CMA) with these MRS as mediators. Next, we conducted a high-dimensional mediation analysis to identify individual CpG sites as potential mediators, followed by a CMA to estimate the average causal mediation effects (ACME) and total effect (TE). PTE and PAE were associated with neurodevelopment at 6 but not at 24 months. PTE MRS reached a prediction accuracy (R) of 0.23 but did not significantly mediate the association between PTE and neurodevelopment. PAE MRS was not predictive of PAE (R = 0.006). For PTE, 31 CpG sites and eight CpG sites were identified as significant mediators (ACME and TE P < 0.05) for the cognitive and motor domains at 6 months, respectively. For PAE, 16 CpG sites and 1 CpG site were significant mediators for the motor and adaptive behavior domains at 6 months, respectively. Several of the associated genes, including MAD1L1, CAMTA1, and ALDH1A2 have been implicated in neurodevelopmental delay, suggesting that differential DNAm may partly explain the biological mechanisms underlying the relationship between PTE and PAE and child neurodevelopment.
产前烟草暴露（PTE）和产前酒精暴露（PAE）与儿童神经发育延迟以及新生儿新生 DNA 甲基化（DNAm）的差异有关。然而，将 PTE 和 PAE、DNAm 和神经发育联系起来的生物学机制在很大程度上尚不清楚。在这里，我们旨在确定差异 DNAm 是否介导 PTE 和 PAE 与南非德肯斯坦儿童健康研究中 6 个月（N=112）和 24 个月（N=184）儿童神经发育之间的关联。PTE 和 PAE 分别在产前使用尿液可替宁测量和 ASSIST 问卷进行评估。使用 EPIC 和 450K BeadChips 测量脐带血 DNAm。使用贝利婴幼儿发展量表第三版测量神经发育（认知、语言、运动、适应行为、社会情感）。我们构建了 PTE 和 PAE 的甲基化风险评分（MRS），并使用这些 MRS 作为中介进行因果中介分析（CMA）。接下来，我们进行了高维中介分析，以确定潜在的中介 CpG 位点，然后进行 CMA 以估计平均因果中介效应（ACME）和总效应（TE）。PTE 和 PAE 与 6 个月时的神经发育有关，但与 24 个月时无关。PTE MRS 达到了 0.23 的预测准确性（R），但并未显著介导 PTE 与神经发育之间的关联。PAE MRS 不能预测 PAE（R=0.006）。对于 PTE，在 6 个月时，31 个 CpG 位点和 8 个 CpG 位点被确定为认知和运动领域的显著中介（ACME 和 TE P<0.05）。对于 PAE，在 6 个月时，16 个 CpG 位点和 1 个 CpG 位点分别为运动和适应行为领域的显著中介。一些相关基因，包括 MAD1L1、CAMTA1 和 ALDH1A2，已被牵连到神经发育迟缓中，这表明差异 DNAm 可能部分解释了 PTE 和 PAE 与儿童神经发育之间关系的生物学机制。
Zotero 插件
