Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5- CHRNA3-CHRNB4) interacts with maternal selfreported smoking status during pregnancy to influence birth weight

Jessica Tyrrell, Ville Huikari, Jennifer T. Christie, Alana Cavadino, Rachel Bakker, Marie Jo A. Brion, Frank Geller, Lavinia Paternoster, Ronny Myhre, Catherine Potter, Paul C.D. Johnson, Shah Ebrahim, Bjarke Feenstra, Anna Liisa Hartikainen, Andrew T. Hattersley, Albert Hofman, Marika Kaakinen, Lynn P. Lowe, Per Magnus, Alex McConnachieMads Melbye, Jane W.Y. Ng, Ellen A. Nohr, Chris Power, Susan M. Ring, Sylvain P. Sebert, Verena Sengpiel, H. Rob Taal, Graham C.M. Watt, Naveed Sattar, Caroline L. Relton, Bo Jacobsson, Timothy M. Frayling, Thorkild I.A. Sørensen, Jeffrey C. Murray, Debbie A. Lawlor, Craig E. Pennell, Vincent W.V. Jaddoe, Elina Hypponen, William L. Lowe, Marjo Riitta Jarvelin, George Davey Smith, Rachel M. Freathy*

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Scopus citations

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 5 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 5 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: 24 to 14 g; P 5 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.

Original languageEnglish (US)
Article numberdds372
Pages (from-to)5344-5358
Number of pages15
JournalHuman molecular genetics
Volume21
Issue number24
DOIs
StatePublished - Dec 1 2012

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Tyrrell, J., Huikari, V., Christie, J. T., Cavadino, A., Bakker, R., Brion, M. J. A., Geller, F., Paternoster, L., Myhre, R., Potter, C., Johnson, P. C. D., Ebrahim, S., Feenstra, B., Hartikainen, A. L., Hattersley, A. T., Hofman, A., Kaakinen, M., Lowe, L. P., Magnus, P., ... Freathy, R. M. (2012). Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5- CHRNA3-CHRNB4) interacts with maternal selfreported smoking status during pregnancy to influence birth weight. Human molecular genetics, 21(24), 5344-5358. [dds372]. https://doi.org/10.1093/hmg/dds372