Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation
Abstract Background Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood...
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2018-04-01
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Online Access: | http://link.springer.com/article/10.1186/s12864-018-4652-7 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Stephanie H. Witt Josef Frank Maria Gilles Maren Lang Jens Treutlein Fabian Streit Isabell A. C. Wolf Verena Peus Barbara Scharnholz Tabea S. Send Stefanie Heilmann-Heimbach Sugirthan Sivalingam Helene Dukal Jana Strohmaier Marc Sütterlin Janine Arloth Manfred Laucht Markus M. Nöthen Michael Deuschle Marcella Rietschel |
spellingShingle |
Stephanie H. Witt Josef Frank Maria Gilles Maren Lang Jens Treutlein Fabian Streit Isabell A. C. Wolf Verena Peus Barbara Scharnholz Tabea S. Send Stefanie Heilmann-Heimbach Sugirthan Sivalingam Helene Dukal Jana Strohmaier Marc Sütterlin Janine Arloth Manfred Laucht Markus M. Nöthen Michael Deuschle Marcella Rietschel Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation BMC Genomics DNA methylation Smoking Birth weight Mediation analysis |
author_facet |
Stephanie H. Witt Josef Frank Maria Gilles Maren Lang Jens Treutlein Fabian Streit Isabell A. C. Wolf Verena Peus Barbara Scharnholz Tabea S. Send Stefanie Heilmann-Heimbach Sugirthan Sivalingam Helene Dukal Jana Strohmaier Marc Sütterlin Janine Arloth Manfred Laucht Markus M. Nöthen Michael Deuschle Marcella Rietschel |
author_sort |
Stephanie H. Witt |
title |
Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation |
title_short |
Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation |
title_full |
Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation |
title_fullStr |
Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation |
title_full_unstemmed |
Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation |
title_sort |
impact on birth weight of maternal smoking throughout pregnancy mediated by dna methylation |
publisher |
BMC |
series |
BMC Genomics |
issn |
1471-2164 |
publishDate |
2018-04-01 |
description |
Abstract Background Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic “smoking methylation pattern”, and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. Methods Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. Results Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top “smoking methylation pattern” genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns. Conclusion The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight. |
topic |
DNA methylation Smoking Birth weight Mediation analysis |
url |
http://link.springer.com/article/10.1186/s12864-018-4652-7 |
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doaj-0c1a0994909f453f9bb40ad194fab9492020-11-25T01:14:47ZengBMCBMC Genomics1471-21642018-04-0119111010.1186/s12864-018-4652-7Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylationStephanie H. Witt0Josef Frank1Maria Gilles2Maren Lang3Jens Treutlein4Fabian Streit5Isabell A. C. Wolf6Verena Peus7Barbara Scharnholz8Tabea S. Send9Stefanie Heilmann-Heimbach10Sugirthan Sivalingam11Helene Dukal12Jana Strohmaier13Marc Sütterlin14Janine Arloth15Manfred Laucht16Markus M. Nöthen17Michael Deuschle18Marcella Rietschel19Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergInstitute of Human Genetics, University of BonnInstitute of Human Genetics, University of BonnDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Gynecology and Obstetrics, Faculty of Medicine Mannheim, University of HeidelbergDepartment of Translational Research in Psychiatry, Max Planck Institute of PsychiatryDepartment of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergInstitute of Human Genetics, University of BonnDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergAbstract Background Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic “smoking methylation pattern”, and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. Methods Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. Results Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top “smoking methylation pattern” genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns. Conclusion The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight.http://link.springer.com/article/10.1186/s12864-018-4652-7DNA methylationSmokingBirth weightMediation analysis |