Evidence map›Paper›PMID 29695247›Full record

ArticleBMC genomics2018

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

Stephanie H Witt, Josef Frank, Maria Gilles, Maren Lang, Jens Treutlein, Fabian Streit, Isabell A C Wolf, Verena Peus, Barbara Scharnholz, Tabea S Send and 10 more

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 5 pooled it
14.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 5 syntheses or guidelines pooled it, 67 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 5 institutions in 1 country.

Stephanie H WittDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. stephanie.witt@zi-mannheim.de.
Josef FrankDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Maria GillesDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Maren LangDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Jens TreutleinDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Fabian StreitDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Isabell A C WolfDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Verena PeusDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Barbara ScharnholzDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Tabea S SendDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Stefanie Heilmann-HeimbachInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Sugirthan SivalingamInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Helene DukalDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Jana StrohmaierDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Marc SütterlinDepartment of Gynecology and Obstetrics, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
Janine ArlothDepartment of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
Manfred LauchtDepartment of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
Markus M NöthenInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Michael DeuschleDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Marcella RietschelDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Central Institute of Mental Health · DEUniversity Hospital Heidelberg · DEHeidelberg University · DEUniversity of Bonn · DEMax Planck Institute of Psychiatry · DE

Funding

Bundesministerium für Bildung und Forschung 01ZX1314ABundesministerium für Bildung und Forschung 01ZX1314GDeutsche Forschungsgemeinschaft FOR2107; RI908/11-1Deutsche Forschungsgemeinschaft NO246/10-1Deutsche Forschungsgemeinschaft WI3429/3-1
6 · The paper itself

Abstract

backgroundCigarette 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.

methodsMethylation 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.

resultsFollowing 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.

conclusionThe 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.

Indexed as

DNA MethylationSmokingAdultBirth WeightCpG IslandsFemaleFetal BloodGenome-Wide Association StudyHumansInfant, NewbornIntegrin beta ChainsMaleMaternal ExposureMembrane ProteinsNerve Tissue ProteinsPregnancyCNTNAP2 protein, humanIntegrin beta ChainsMembrane ProteinsNerve Tissue ProteinsPIM1 protein, humanProto-Oncogene Proteins c-pim-1Birth weightDNA methylationMediation analysisSmoking

Identifiers

PMID29695247
PMCPMC5922319
OpenAlexW2804204989

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.