4.6 Article

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

期刊

CLINICAL EPIGENETICS
卷 11, 期 -, 页码 -

出版社

BMC
DOI: 10.1186/s13148-019-0683-4

关键词

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

资金

  1. Academy of Finland EGEA-project [285547]
  2. Biocenter, University of Oulu, Finland [75617]
  3. NHLBI grant through the STAMPEED program [5R01HL087679-02, 1RL1MH083268-01]
  4. ERDF European Regional Development Fund [539/2010 A31592]
  5. EU H2020-PHC-2014 DynaHEALTH action [633595]
  6. EU H2020-HCO-2004 iHEALTH Action [643774]
  7. EU H2020-PHC-2014 ALEC Action [633212]
  8. EU H2020-SC1-2016-2017 LifeCycle Action [733206]
  9. EU H2020-MSCA-ITN-2016 CAPICE Action [721567]
  10. MRC [MR/M013138/1]
  11. National Institutes of Health USA [R01 HL082925, R01 AI091905, R01 HL132321, R01 AI121226]
  12. Asthma UK [364]
  13. Ageing Lungs in European Cohorts (ALEC) Study - European Union's Horizon 2020 Research and Innovation programme [633212]
  14. Integrative Epidemiology Unit - UK Medical Research Council
  15. University of Bristol [MC_UU_12013_1, MC_UU_12013_2]
  16. CRUK [C18281/A19169]
  17. ESRC [ES/N000498/1]
  18. UK Medical Research Council [102215/2/13/2]
  19. Wellcome Trust [102215/2/13/2, WT088806]
  20. UK Biotechnology and Biological Sciences Research Council [BB/I025751/1, BB/I025263/1]
  21. BBSRC [BB/I025751/1, BB/I025263/1] Funding Source: UKRI
  22. ESRC [ES/N000498/1] Funding Source: UKRI
  23. MRC [MR/M013138/2, MC_UU_00011/1, MR/S003886/1, MC_UU_12013/2, MR/M013138/1, MC_UU_00011/5, MC_PC_19009] Funding Source: UKRI
  24. Academy of Finland (AKA) [285547, 285547] Funding Source: Academy of Finland (AKA)

向作者/读者索取更多资源

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 48years) 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 x 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.

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