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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

Lookup NU author(s): Dr Kate Potter, Dr Jane Ng, Professor Caroline Relton

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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): 436 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: 4to 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.

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Author(s): Tyrrell J, Huikari V, Christie JT, Cavadino A, Bakker R, Brion MJA, Geller F, Paternoster L, Myhre R, Potter C, Johnson PCD, Ebrahim S, Feenstra B, Hartikainen AL, Hattersley AT, Hofman A, Kaakinen M, Lowe LP, Magnus P, McConnachie A, Melbye M, Ng JWY, Nohr EA, Power C, Ring SM, Sebert SP, Sengpiel V, Taal HR, Watt GCM, Sattar N, Relton CL, Jacobsson B, Frayling TM, Srensen TIA, Murray JC, Lawlor DA, Pennell CE, Jaddoe VWV, Hypponen E, Lowe WL, Jarvelin MR, Smith GD, Freathy RM, Early Growth Genetics EGG

Publication type: Article

Publication status: Published

Journal: Human Molecular Genetics

Year: 2012

Volume: 21

Issue: 24

Pages: 5344-5358

Print publication date: 05/09/2012

ISSN (print): 0964-6906

ISSN (electronic): 1460-2083

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/hmg/dds372

DOI: 10.1093/hmg/dds372

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