@article{815f1e07980c4b09af882d037e01b302,
title = "DNA methylation links prenatal smoking exposure to later life health outcomes in offspring",
abstract = "BACKGROUND: Maternal 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.METHODS: We 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.RESULTS: We 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. CONCLUSIONS: DNA methylation may represent a biological mechanism through which maternal smoking is associated with increased risk of psychiatric morbidity in the exposed offspring.",
keywords = "Causality, DNA methylation, Disease, Life course, Maternal smoking, Mediation, Persistence, Pregnancy, Schizophrenia/chemically induced, Prospective Studies, Epigenesis, Genetic, Humans, Middle Aged, Smoking/adverse effects, Young Adult, DNA Methylation, Prenatal Exposure Delayed Effects/chemically induced, Mendelian Randomization Analysis, Adult, Female, Maternal Exposure/adverse effects, GTP-Binding Protein gamma Subunits/genetics, Genome-Wide Association Study, Adolescent, CpG Islands, Longitudinal Studies, Cohort Studies",
author = "Petri Wiklund and Ville Karhunen and Richmond, {Rebecca C.} and Priyanka Parmar and Alina Rodriguez and Silva, {Maneka De} and Matthias Wielscher and Rezwan, {Faisal I} and Richardson, {Tom G.} and Juha Veijola and Karl-Heinz Herzig and Holloway, {John W.} and Relton, {Caroline L.} and Sylvain Sebert and Marjo-Riitta J{\"a}rvelin",
note = "Funding Information: This project was supported by the Academy of Finland EGEA-project (285547), Biocenter, University of Oulu, Finland (75617), NHLBI grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01), ERDF European Regional Development Fund grant no. 539/2010 A31592, the EU H2020--PHC-2014 DynaHEALTH action (grant agreements no. 633595), EU H2020-HCO-2004 iHEALTH Action (grant agreement 643774), EU H2020-PHC-2014 ALEC Action (grant agreement no. 633212), EU H2020-SC1-2016-2017 LifeCycle Action (grant agreement no. 733206), EU H2020-MSCA-ITN-2016 CAPICE Action (grant agreement 721567) and MRC grant no. MR/M013138/1. The Isle of Wight Birth Cohort study has been supported by the National Institutes of Health USA (grant no. R01 HL082925 (PI: Arshad), R01 AI091905 and R01 HL132321 (PI: Karmaus), and R01 AI121226 (MPI: Zhang and Holloway) and Asthma UK (grant no. 364). JWH and FIR are supported by the Ageing Lungs in European Cohorts (ALEC) Study (www.alecstudy.org), which has been funded by the European Union{\textquoteright}s Horizon 2020 Research and Innovation programme under grant agreement no. 633212. Data contributions by the ALSPAC study were supported by the Integrative Epidemiology Unit, which receives funding from the UK Medical Research Council and the University of Bristol (MC_UU_12013_1 and MC_UU_12013_2). This work was also supported by CRUK (grant number C18281/A19169) and the ESRC (grant number ES/N000498/1). The UK Medical Research Council and the Wellcome Trust (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. The Accessible Resource for Integrated Epigenomics Studies (ARIES) was funded by the UK Biotechnology and Biological Sciences Research Council (BB/I025751/1 and BB/I025263/1). R.C.R is a de Pass VC Research Fellow at the University of Bristol. T.G.R is a UKRI Innovation Research Fellow (MR/S003886/1). GWAS data used to identify the mQTLs for the ALSPAC offspring was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. Genotyping for the ALSPAC women was supported by the Wellcome Trust (grant reference WT088806). A comprehensive list of grant funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/ documents/grant-acknowledgements.pdf). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2019 The Author(s).",
year = "2019",
month = jul,
day = "1",
doi = "10.1186/s13148-019-0683-4",
language = "English",
volume = "11",
journal = "Clinical epigenetics",
issn = "1868-7083",
publisher = "Springer Nature",
number = "1",
}