Cosin-Tomas Marta, Hoang Thanh, Qi Cancan, Monasso Giulietta S, Langdon Ryan, Kebede Merid Simon, Calas Lucinda, de Prado-Bert Paula, Richmond Rebecca, Jaddoe Vincent Vw, Duijts Liesbeth, Wright John, Annesi-Maesano Isabella, Grazuleviciene Regina, Karachaliou Marianna, Koppelman Gerard H, Melén Erik, Gruzieva Olena, Vrijheid Martine, Yousefi Paul, Felix Janine F, London Stephanie J, Bustamante Mariona
ISGlobal, Barcelona, Catalonia, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain; Centro de investigación biomédica en red en epidemiología y salud pública (CIBERESP), Madrid, Spain.
Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA; Department of Pediatrics, Division of Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA; Cancer and Hematology Center, Texas Children's Hospital, Houston, TX, USA.
Environ Int. 2025 Jan;195:109204. doi: 10.1016/j.envint.2024.109204. Epub 2024 Dec 10.
By recent estimates, 40% of children worldwide are exposed to second-hand smoke (SHS), which has been associated with adverse health outcomes. While numerous studies have linked maternal smoking during pregnancy (MSDP) to widespread differences in child blood DNA methylation (DNAm), research specifically examining postnatal SHS exposure remains sparse. To address this gap, we conducted epigenome-wide meta-analyses to identify associations of postnatal SHS and child blood DNAm.
Six cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium (total N = 2,695), with SHS data and child blood DNAm (aged 7-9 years) measured with the Illumina 450K array were included in the meta-analysis. Linear regression models adjusted for covariates were fitted to examine the association between the number of household smokers in postnatal life (0, 1, 2+) and child blood DNAm. Sensitivity models without adjusting for MSDP and restricted to mothers who did not smoke during pregnancy were evaluated.
Our analysis revealed significant associations (False Discovery Rate < 0.05) between household postnatal SHS exposure and DNAm at 11 CpGs in exposed children. Nine CpGs were mapped to genes (MYO1G, FAM184B, CTDSPL2, LTBP3, PDE10A, and FIBCD1), while 2 CpGs were located in open sea regions. Notably, all except 2 CpGs (mapped to FIBCD1 and CTDSPL2) have previously been linked to either personal smoking habits or in utero exposure to smoking. The models restricted to non-smoking mothers provided similar results. Importantly, several of these CpGs and their associated genes are implicated in conditions exacerbated by or directly linked to SHS.
Our findings highlight the potential biological effects of SHS on blood DNAm. These findings support further research on epigenetic factors mediating deleterious effects of SHS on child health and call for public health policies aimed at reducing exposure, particularly in environments where children are present.
据近期估计，全球40%的儿童暴露于二手烟（SHS）中，这与不良健康后果相关。虽然众多研究已将孕期母亲吸烟（MSDP）与儿童血液DNA甲基化（DNAm）的广泛差异联系起来，但专门研究产后二手烟暴露的研究仍然很少。为了填补这一空白，我们进行了全表观基因组荟萃分析，以确定产后二手烟暴露与儿童血液DNAm之间的关联。
来自妊娠与儿童表观遗传学（PACE）联盟的六个队列（总计N = 2695）被纳入荟萃分析，这些队列具有二手烟数据以及使用Illumina 450K芯片测量的儿童血液DNAm（年龄7 - 9岁）。拟合调整协变量的线性回归模型，以检验产后家庭吸烟者数量（0、1、2+）与儿童血液DNAm之间的关联。评估了未调整MSDP且仅限于孕期不吸烟母亲的敏感性模型。
我们的分析揭示了产后家庭二手烟暴露与受暴露儿童中11个CpG位点的DNAm之间存在显著关联（错误发现率<0.05）。9个CpG位点映射到基因（MYO1G、FAM184B、CTDSPL2、LTBP3、PDE10A和FIBCD1），而2个CpG位点位于基因荒漠区域。值得注意的是，除了2个CpG位点（映射到FIBCD1和CTDSPL2）外，所有其他位点此前都与个人吸烟习惯或子宫内吸烟暴露有关。仅限于不吸烟母亲的模型提供了类似的结果。重要的是，这些CpG位点中的几个及其相关基因与二手烟加剧或直接相关的疾病有关。
我们的研究结果突出了二手烟对血液DNAm的潜在生物学影响。这些发现支持进一步研究介导二手烟对儿童健康有害影响的表观遗传因素，并呼吁制定旨在减少暴露的公共卫生政策，特别是在有儿童的环境中。
