{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:53:22Z","timestamp":1761720802596,"version":"build-2065373602"},"reference-count":43,"publisher":"CSIRO Publishing","issue":"7","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":1204,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,12]]},"abstract":"<jats:p>Maternal tobacco smoking during pregnancy is a large driver of health inequalities and a higher prevalence of conduct problem (CP) has been observed in exposed offspring. Further, maternal tobacco use during pregnancy can also alter offspring DNA methylation. However, currently, limited molecular evidence has been found to support this observation. Thus we aim to examine the association between maternal tobacco use in pregnancy and offspring CP, to determine whether offspring CP is mediated by tobacco exposure-induced DNA methylation differences. Understanding the etiology of the association between maternal tobacco use and offspring CP will be crucial in the early identification and treatment of CP in children and adolescents. Here, a sub group of N\u00a0=\u00a096 individuals was sourced from the Christchurch Health and Development Study, a longitudinal birth cohort studied for over 40 years in New Zealand. Whole blood samples underwent bisulphite-based amplicon sequencing at 10 loci known to play a role in neurodevelopment, or which had associations with CP phenotypes. We identified significant (P\u00a0&amp;lt;\u00a00.05) differential DNA methylation at specific CpG sites in CYP1A1, ASH2L and MEF2C in individuals with CP who were exposed to tobacco in utero. We conclude that environmentally-induced DNA methylation differences could play a role in the observed link between maternal tobacco use during pregnancy and childhood\/adolescent CP. However, larger sample sizes are needed to produce an adequate amount of power to investigate this interaction further.<\/jats:p>","DOI":"10.1071\/rd21108","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T17:15:30Z","timestamp":1644254130000},"page":"540-548","source":"Crossref","is-referenced-by-count":4,"title":["DNA methylation analysis using bisulphite-based amplicon sequencing of individuals exposed to maternal tobacco use during pregnancy, and offspring conduct problems in childhood and adolescence\u2020"],"prefix":"10.1071","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7380-2248","authenticated-orcid":true,"given":"Alexandra J.","family":"Noble","sequence":"first","affiliation":[{"name":"ASchool of Biological Sciences, University of Canterbury, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John F.","family":"Pearson","sequence":"additional","affiliation":[{"name":"BDepartment of Pathology and Biomedical Sciences, University of Otago, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2292-8216","authenticated-orcid":true,"given":"Alasdair D.","family":"Noble","sequence":"additional","affiliation":[{"name":"CAgResearch, Lincoln Research Centre, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph M.","family":"Boden","sequence":"additional","affiliation":[{"name":"DDepartment of Psychological Medicine, University of Otago, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. John","family":"Horwood","sequence":"additional","affiliation":[{"name":"DDepartment of Psychological Medicine, University of Otago, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin A.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"BDepartment of Pathology and Biomedical Sciences, University of Otago, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy J.","family":"Osborne","sequence":"additional","affiliation":[{"name":"ASchool of Biological Sciences, University of Canterbury, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"67","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"key":"2025102820251684800_R1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/01.GIM.0000110413.07490.0B","article-title":"Attention deficit\/hyperactivity disorder (ADHD): complex phenotype, simple genotype?","volume":"6","author":"Acosta","year":"2004","journal-title":"Genetics in Medicine"},{"key":"2025102820251684800_R2","doi-asserted-by":"publisher","DOI":"10.1186\/1744-9081-3-30","article-title":"A gene\u00a0\u00d7\u00a0gene interaction between DRD2 and DRD4 is associated with conduct disorder and antisocial behavior in males.","volume":"3","author":"Beaver","year":"2007","journal-title":"Behavioral and Brain Functions"},{"key":"2025102820251684800_R3","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.earlhumdev.2007.03.009","article-title":"Maternal smoking during pregnancy and behaviour problems in a birth cohort of 2-year-old Pacific children in New Zealand.","volume":"84","author":"Carter","year":"2008","journal-title":"Early Human Development"},{"key":"2025102820251684800_R4","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.12688\/f1000research.13196.1","article-title":"Differential methylation analysis of reduced representation bisulfite sequencing experiments using edger.","volume":"6","author":"Chen","year":"2017","journal-title":"F1000Res"},{"key":"2025102820251684800_R5","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1176\/ajp.126.6.884","article-title":"A teacher rating scale for use in drug studies with children.","volume":"126","author":"Conners","year":"1969","journal-title":"American Journal of Psychiatry"},{"key":"2025102820251684800_R6","doi-asserted-by":"publisher","first-page":"667","DOI":"10.2307\/1127215","article-title":"Symptom patterns in hyperkinetic, neurotic, and normal children.","volume":"41","author":"Conners","year":"1970","journal-title":"Child Development"},{"key":"2025102820251684800_R7","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-485","article-title":"SolexaQA: at-a-glance quality assessment of Illumina second-generation sequencing data.","volume":"11","author":"Cox","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2025102820251684800_R8","doi-asserted-by":"publisher","first-page":"14461","DOI":"10.3390\/ijerph121114461","article-title":"Assessment of offspring DNA methylation across the lifecourse associated with prenatal maternal smoking using Bayesian mixture modelling.","volume":"12","author":"De Vocht","year":"2015","journal-title":"International Journal of Environmental Research and Public Health"},{"issue":"1","key":"2025102820251684800_R45","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41588-018-0269-7","article-title":"Discovery of the first genome-wide significant risk loci for attention deficit\/hyperactivity disorder.","volume":"51","author":"Demontis","year":"2019","journal-title":"Nature Genetics"},{"key":"2025102820251684800_R10","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1111\/j.1469-7610.1991.tb00305.x","article-title":"Confirmatory factor models of attention deficit and conduct disorder.","volume":"32","author":"Fergusson","year":"1991","journal-title":"Journal of Child Psychology and Psychiatry, and Allied Disciplines"},{"key":"2025102820251684800_R11","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1111\/j.1469-7610.2004.00387.x","article-title":"Show me the child at seven: the consequences of conduct problems in childhood for psychosocial functioning in adulthood.","volume":"46","author":"Fergusson","year":"2005","journal-title":"Journal of Child Psychology and Psychiatry, and Allied Disciplines"},{"key":"2025102820251684800_R12","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.20059","article-title":"MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders.","volume":"5","author":"Harrington","year":"2016","journal-title":"eLife"},{"key":"2025102820251684800_R13","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1093\/ntr\/ntq157","article-title":"CYP1A1 modifies the effect of maternal exposure to environmental tobacco smoke on child behavior.","volume":"12","author":"Hsieh","year":"2010","journal-title":"Nicotine & Tobacco Research"},{"key":"2025102820251684800_R14","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.186","article-title":"Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer\u2019s disease.","volume":"6","author":"Jiao","year":"2016","journal-title":"Translational Psychiatry"},{"key":"2025102820251684800_R15","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-016-1007-2","article-title":"Prenatal smoking exposure and neuropsychiatric comorbidity of ADHD: a finnish nationwide population-based cohort study.","volume":"16","author":"Joelsson","year":"2016","journal-title":"BMC Psychiatry"},{"key":"2025102820251684800_R16","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1289\/ehp.1205412","article-title":"450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy.","volume":"120","author":"Joubert","year":"2012","journal-title":"Environmental Health Perspectives"},{"key":"2025102820251684800_R17","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.ajhg.2016.02.019","article-title":"DNA methylation in newborns and maternal smoking in pregnancy: genome-wide consortium meta-analysis.","volume":"98","author":"Joubert","year":"2016","journal-title":"The American Journal of Human Genetics"},{"key":"2025102820251684800_R18","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1038\/nn.4315","article-title":"An epigenetic mechanism mediates developmental nicotine effects on neuronal structure and behavior.","volume":"19","author":"Jung","year":"2016","journal-title":"Nature Neuroscience"},{"key":"2025102820251684800_R19","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/nature03701","article-title":"Oxytocin increases trust in humans.","volume":"435","author":"Kosfeld","year":"2005","journal-title":"Nature"},{"key":"2025102820251684800_R20","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1093\/bioinformatics\/btr167","article-title":"Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications.","volume":"27","author":"Krueger","year":"2011","journal-title":"Bioinformatics"},{"key":"2025102820251684800_R21","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1001\/jama.279.21.1703","article-title":"Socioeconomic factors, health behaviors, and mortality results from a nationally representative prospective study of US Adults\u2019.","volume":"279","author":"Lantz","year":"1998","journal-title":"JAMA"},{"key":"2025102820251684800_R22","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1289\/ehp.1408614","article-title":"Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age.","volume":"123","author":"Lee","year":"2015","journal-title":"Environmental Health Perspectives"},{"key":"2025102820251684800_R23","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1016\/j.celrep.2019.06.055","article-title":"The COMPASS family protein ASH2L mediates corticogenesis via transcriptional regulation of wnt signaling.","volume":"28","author":"Li","year":"2019","journal-title":"Cell Reports"},{"key":"2025102820251684800_R24","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.mce.2018.06.013","article-title":"Oxytocin alters the morphology of hypothalamic neurons via the transcription factor myocyte enhancer factor 2A (MEF-2A).","volume":"477","author":"Meyer","year":"2018","journal-title":"Molecular and Cellular Endocrinology"},{"key":"2025102820251684800_R25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21062200","article-title":"Myocyte Enhancer Factor 2A (MEF2A) defines oxytocin-induced morphological effects and regulates mitochondrial function in neurons.","volume":"21","author":"Meyer","year":"2020","journal-title":"International Journal of Molecular Sciences"},{"key":"2025102820251684800_R26","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1097\/00004583-200204000-00009","article-title":"Case-control study of attention-deficit hyperactivity disorder and maternal smoking, alcohol use, and drug use during pregnancy.","volume":"41","author":"Mick","year":"2002","journal-title":"Journal of the American Academy of Child & Adolescent Psychiatry"},{"key":"2025102820251684800_R46","doi-asserted-by":"publisher","first-page":"e10762","DOI":"10.7717\/peerj.10762","article-title":"A validation of Illumina EPIC array system with bisulfite-based amplicon sequencing.","volume":"9","author":"Noble","year":"2021","journal-title":"PeerJ"},{"key":"2025102820251684800_R29","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00770","article-title":"Maternal smoking during pregnancy induces persistent epigenetic changes into adolescence, independent of postnatal smoke exposure and is associated with cardiometabolic risk.","volume":"10","author":"Rauschert","year":"2019","journal-title":"Frontiers in Genetics"},{"key":"2025102820251684800_R30","doi-asserted-by":"publisher","first-page":"2201","DOI":"10.1093\/hmg\/ddu739","article-title":"Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC).","volume":"24","author":"Richmond","year":"2015","journal-title":"Human Molecular Genetics"},{"key":"2025102820251684800_R31","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1093\/ije\/dyy091","article-title":"DNA methylation as a marker for prenatal smoke exposure in adults.","volume":"47","author":"Richmond","year":"2018","journal-title":"International Journal of Epidemiology"},{"key":"2025102820251684800_R32","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1007\/s00787-014-0627-7","article-title":"GRIN2B predicts attention problems among disadvantaged children.","volume":"24","author":"Riva","year":"2015","journal-title":"European Child & Adolescent Psychiatry"},{"key":"2025102820251684800_R33","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-016-3310-1","article-title":"Maternal smoking impacts key biological pathways in newborns through epigenetic modification in utero.","volume":"17","author":"Rotroff","year":"2016","journal-title":"BMC Genomics"},{"key":"2025102820251684800_R34"},{"key":"2025102820251684800_R35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0155554","article-title":"Maternal smoking during pregnancy and DNA-methylation in children at age 5.5 years: epigenome-wide-analysis in the European Childhood Obesity Project (CHOP)-study.","volume":"11","author":"Rzehak","year":"2016","journal-title":"PLoS ONE"},{"key":"2025102820251684800_R36","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.neubiorev.2016.06.034","article-title":"Genetic influences on conduct disorder.","volume":"91","author":"Salvatore","year":"2018","journal-title":"Neuroscience & Biobehavioral Reviews"},{"key":"2025102820251684800_R37","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.psychres.2017.06.048","article-title":"Locus-specific DNA methylation changes and phenotypic variability in children with attention-deficit hyperactivity disorder.","volume":"256","author":"Sengupta","year":"2017","journal-title":"Psychiatry Research"},{"key":"2025102820251684800_R38","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-019-0587-2","article-title":"Reduced neonatal brain-derived neurotrophic factor is associated with autism spectrum disorders.","volume":"9","author":"Skogstrand","year":"2019","journal-title":"Translational Psychiatry"},{"key":"2025102820251684800_R39","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1016\/j.metabol.2010.01.013","article-title":"In utero tobacco exposure epigenetically modifies placental CYP1A1 expression.","volume":"59","author":"Suter","year":"2010","journal-title":"Metabolism-Clinical and Experimental"},{"key":"2025102820251684800_R40","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1080\/15592294.2017.1325065","article-title":"Maternal cigarette smoking during pregnancy and offspring DNA methylation in midlife.","volume":"13","author":"Tehranifar","year":"2018","journal-title":"Epigenetics"},{"key":"2025102820251684800_R41","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1080\/15592294.2017.1361592","article-title":"Locus-specific DNA methylation in the placenta is associated with levels of pro-inflammatory proteins in cord blood and they are both independently affected by maternal smoking during pregnancy.","volume":"12","author":"van Otterdijk","year":"2017","journal-title":"Epigenetics"},{"key":"2025102820251684800_R42","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.devcel.2007.03.007","article-title":"The transcription factor MEF2C is required for craniofacial development.","volume":"12","author":"Verzi","year":"2007","journal-title":"Developmental Cell"},{"key":"2025102820251684800_R43","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1001\/archpsyc.1997.01830190098010","article-title":"Maternal smoking during pregnancy and the risk of conduct disorder in boys.","volume":"54","author":"Wakschlag","year":"1997","journal-title":"Archives of General Psychiatry"},{"key":"2025102820251684800_R44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001128","article-title":"Oxytocin increases generosity in humans.","volume":"2","author":"Zak","year":"2007","journal-title":"PLoS ONE"}],"container-title":["Reproduction, Fertility and Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/connectsci.au\/rd\/article-pdf\/34\/7\/540\/319206\/rd21108.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/connectsci.au\/rd\/article-pdf\/34\/7\/540\/319206\/rd21108.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:25:25Z","timestamp":1761697525000},"score":1,"resource":{"primary":{"URL":"https:\/\/connectsci.au\/rd\/article\/34\/7\/540\/50936\/DNA-methylation-analysis-using-bisulphite-based"}},"subtitle":[],"editor":[{"given":"Alison","family":"Care","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,2,8]]},"references-count":43,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,4,12]]}},"URL":"https:\/\/doi.org\/10.1071\/rd21108","relation":{},"ISSN":["1031-3613","1448-5990"],"issn-type":[{"type":"print","value":"1031-3613"},{"type":"electronic","value":"1448-5990"}],"subject":[],"published":{"date-parts":[[2022,2,8]]}}}