Association of exposure to second-hand smoke during childhood with blood DNA methylation

Marta Cosin-Tomas; Thanh Hoang; Cancan Qi; Giulietta S Monasso; Ryan Langdon; Simon Kebede Merid; Lucinda Calas; Paula de Prado-Bert; Rebecca Richmond; Vincent Vw Jaddoe; Liesbeth Duijts; John Wright; Isabella Annesi-Maesano; Regina Grazuleviciene; Marianna Karachaliou; Gerard H Koppelman; Erik Melén; Olena Gruzieva; Martine Vrijheid; Paul Yousefi; Janine F Felix; Stephanie J London; Mariona Bustamante; Pregnancy And Childhood Epigenetics (PACE) Consortium

doi:10.1016/j.envint.2024.109204

Association of exposure to second-hand smoke during childhood with blood DNA methylation

Environ Int. 2024 Dec 10:195:109204. doi: 10.1016/j.envint.2024.109204. Online ahead of print.

Authors

Marta Cosin-Tomas¹, Thanh Hoang², Cancan Qi³, Giulietta S Monasso⁴, Ryan Langdon⁵, Simon Kebede Merid⁶, Lucinda Calas⁷, Paula de Prado-Bert⁸, Rebecca Richmond⁵, Vincent Vw Jaddoe⁴, Liesbeth Duijts⁹, John Wright¹⁰, Isabella Annesi-Maesano⁷, Regina Grazuleviciene¹¹, Marianna Karachaliou¹², Gerard H Koppelman¹³, Erik Melén¹⁴, Olena Gruzieva¹⁵, Martine Vrijheid⁸, Paul Yousefi¹⁶, Janine F Felix¹⁷, Stephanie J London¹⁸, Mariona Bustamante⁸; Pregnancy And Childhood Epigenetics (PACE) Consortium

Affiliations

¹ 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. Electronic address: [email protected].
² 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.
³ Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands; Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Microbiome Medicine Center, Department of Laboratory Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou, China.
⁴ The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁵ Medical Research Council Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Bristol, UK; Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
⁶ Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
⁷ Université Paris Cité and Université Sorbonne Paris Nord, Inserm, INRAE, Center for Research in Epidemiology and StatisticS (CRESS), F-75004, Paris, France.
⁸ 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.
⁹ The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Neonatal and Pediatric Intensive Care, division of Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
¹⁰ Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
¹¹ Department of Environmental Sciences, Vytautas Magnus University, Kaunas, Lithuania.
¹² ISGlobal, Barcelona, Catalonia, Spain; Clinic of preventive and Social Medicine, Medical School, University of Crete, Iraklio, Greece.
¹³ Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands; Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
¹⁴ Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Sachs' Children's Hospital, Stockholm, Sweden.
¹⁵ Centre for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
¹⁶ Medical Research Council Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Bristol, UK; Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK; NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol, Bristol, UK.
¹⁷ The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. Electronic address: [email protected].
¹⁸ Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.

PMID: 39693780
DOI: 10.1016/j.envint.2024.109204

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: 450K array; Children; DNA methylation; Maternal smoking during pregnancy; Passive smoking; Postnatal exposure; blood DNA methylation.