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

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 Aagaard Nøhr, 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, Early Growth Genetics (EGG) Consortium

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Abstrakt

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.
OriginalsprogEngelsk
TidsskriftHuman Molecular Genetics
Vol/bind21
Udgave nummer24
Sider (fra-til)5344-58
Antal sider15
ISSN0964-6906
DOI
StatusUdgivet - dec. 2012
Udgivet eksterntJa

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  • Citationsformater

    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., ... Early Growth Genetics (EGG) Consortium (2012). 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. Human Molecular Genetics, 21(24), 5344-58. https://doi.org/10.1093/hmg/dds372