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Type: Journal article
Title: Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight
Author: Tyrrell, J.
Huikari, V.
Christie, J.
Cavadino, A.
Bakker, R.
Brion, M.
Geller, F.
Paternoster, L.
Myhre, R.
Potter, C.
Johnson, P.
Ebrahim, S.
Feenstra, B.
Hartikainen, A.
Hattersley, A.
Hofman, A.
Kaakinen, M.
Lowe, L.
Magnus, P.
McConnachie, A.
et al.
Citation: Human Molecular Genetics, 2012; 21(24):5344-5358
Publisher: Oxford University Press
Issue Date: 2012
ISSN: 0964-6906
Statement of
Jessica Tyrrell ... Debbie A. Lawlor ... et al. for the Early Growth Genetics (EGG) Consortium
Abstract: Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P = 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P = 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: -4 to 14 g; P = 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight.
Keywords: Early Growth Genetics (EGG) Consortium
Receptors, Nicotinic
Rights: © The Author 2012. Published by Oxford University Press. All rights reserved. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI: 10.1093/hmg/dds372
U01 DK062418
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