NDLI: Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation

Content Provider	Springer Nature : BioMed Central
Author	Witt, Stephanie H. Frank, Josef Gilles, Maria Lang, Maren Treutlein, Jens Streit, Fabian Wolf, Isabell A. C. Peus, Verena Scharnholz, Barbara Send, Tabea S. Heilmann-Heimbach, Stefanie Sivalingam, Sugirthan Dukal, Helene Strohmaier, Jana Sütterlin, Marc Arloth, Janine Laucht, Manfred Nöthen, Markus M. Deuschle, Michael Rietschel, Marcella
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.
Related Links	https://bmcgenomics.biomedcentral.com/counter/pdf/10.1186/s12864-018-4652-7.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	14712164
DOI	10.1186/s12864-018-4652-7
Journal	BMC Genomics
Issue Number	1
Volume Number	19
Language	English
Publisher	BioMed Central
Publisher Date	2018-04-25
Access Restriction	Open
Subject Keyword	Life Sciences Microarrays Proteomics Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics DNA methylation Smoking Birth weight Mediation analysis
Content Type	Text
Resource Type	Article
Subject	Biotechnology Genetics
Journal Impact Factor	3.5/2023
5-Year Journal Impact Factor	4.1/2023

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