DNA methylation links prenatal smoking exposure to later life health outcomes in offspring

Clinical Epigenetics

  ^{1    2    3    4    5    5    5    6    7    7    7    8    9    1,10    1,11} 

[1] 0000 0001 0941 4873, grid.10858.34, Center for Life Course Health Research, University of Oulu, Oulu, Finland;0000 0001 0941 4873, grid.10858.34, Center for Life Course Health Research, University of Oulu, Oulu, Finland;0000 0001 0941 4873, grid.10858.34, Institute of Biomedicine and Biocenter of Oulu, Oulu, Finland;0000 0001 2113 8111, grid.7445.2, Department for Genomics of Common Diseases, School of Medicine, Imperial College London, London, UK;0000 0001 0941 4873, grid.10858.34, Center for Life Course Health Research, University of Oulu, Oulu, Finland;0000 0001 2113 8111, grid.7445.2, Department of Epidemiology and Biostatistics, Imperial College London, London, UK;0000 0001 1013 7965, grid.9681.6, Department of Health Sciences, University of Jyvaskyla, Jyvaskyla, Finland;0000 0001 0941 4873, grid.10858.34, Center for Life Course Health Research, University of Oulu, Oulu, Finland;0000 0001 2113 8111, grid.7445.2, Department of Epidemiology and Biostatistics, Imperial College London, London, UK;0000 0004 4685 4917, grid.412326.0, Oulu University Hospital, Oulu, Finland;0000 0001 0941 4873, grid.10858.34, Institute of Biomedicine and Biocenter of Oulu, Oulu, Finland;0000 0001 2113 8111, grid.7445.2, MRC-PHE Centre for Environment and Health, Imperial College London, W2 1PG, London, UK;0000 0001 0724 6933, grid.7728.a, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK;0000 0001 2113 8111, grid.7445.2, Department of Epidemiology and Biostatistics, Imperial College London, London, UK;0000 0001 2113 8111, grid.7445.2, Department of Epidemiology and Biostatistics, Imperial College London, London, UK;0000 0004 0420 4262, grid.36511.30, School of Psychology, University of Lincoln, Lincoln, UK;0000 0004 1936 7603, grid.5337.2, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK;0000 0004 1936 9297, grid.5491.9, Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK;0000 0004 1936 9297, grid.5491.9, Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK;0000 0004 1936 9297, grid.5491.9, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK;Medical Research Center Oulu, Oulu, Finland;0000 0004 4685 4917, grid.412326.0, Oulu University Hospital, Oulu, Finland;0000 0001 0941 4873, grid.10858.34, Institute of Biomedicine and Biocenter of Oulu, Oulu, Finland;0000 0001 2205 0971, grid.22254.33, Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland;Medical Research Center Oulu, Oulu, Finland;0000 0004 4685 4917, grid.412326.0, Oulu University Hospital, Oulu, Finland;0000 0001 0941 4873, grid.10858.34, Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland;

关键词: Maternal smoking;    Pregnancy;    DNA methylation;    Persistence;    Mediation;    Disease;    Causality;    Life course;   

DOI  :  10.1186/s13148-019-0683-4

来源: publisher

【 摘 要 】

BackgroundMaternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship.MethodsWe examined the association of prenatal maternal smoking with offspring blood DNA methylation in 2821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess whether methylation markers have causal effects on disease outcomes in the offspring.ResultsWe identify 69 differentially methylated CpGs in 36 genomic regions (P value < 1 × 10−7) associated with exposure to maternal smoking in adolescents and adults. Mendelian randomization analyses provided evidence for a causal role of four maternal smoking-related CpG sites on an increased risk of inflammatory bowel disease or schizophrenia. Further mediation analyses showed some evidence of cg25189904 in GNG12 gene mediating the effect of exposure to maternal smoking on schizophrenia-related outcomes.ConclusionsDNA methylation may represent a biological mechanism through which maternal smoking is associated with increased risk of psychiatric morbidity in the exposed offspring.

【 授权许可】

CC BY