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
Tyrrell, Jessica S.
Hattersley, Andrew T.
Frayling, Timothy M.
Davey Smith, G
Early Growth Genetics (EGG) Consortium
Human Molecular Genetics
Oxford University Press
Reason for embargo
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.
notes: PMCID: PMC3516066
This is a pre-copyedited, author-produced PDF of an article accepted for publication in Human Molecular Genetics following peer review. The definitive publisher-authenticated version is available online at: http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=22956269.
The Supplementary File contains: i) Supplementary Table 1: Genotyping quality control data by study. ii) Supplementary Table 2: Associations between maternal rs1051730 genotype and birth weight in the individual studies, stratified by pregnancy smoking status. iii) Supplementary Figure 1: Meta-analysis plot of the association between fetal rs1051730 genotype and offspring birth weight, stratified by maternal smoking status. iv) Supplementary Note: List of members of the Early Growth Genetics (EGG) Consortium, and their affiliations.
Vol. 21, Issue 24, pp. 5344 - 5358
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