Tyrrell, Jessica4; Huikari, Ville4; Christie, Jennifer T4; Cavadino, Alana4; Bakker, Rachel4; Brion, Marie-Jo A4; Geller, Frank4; Paternoster, Lavinia4; Myhre, Ronny4; Potter, Catherine4; Johnson, Paul C D4; Ebrahim, Shah4; Feenstra, Bjarke4; Hartikainen, Anna-Liisa4; Hattersley, Andrew T4; Hofman, Albert4; Kaakinen, Marika4; Lowe, Lynn P4; Magnus, Per4; McConnachie, Alex4; Melbye, Mads4; Ng, Jane W Y4; Nohr, Ellen A4; Power, Chris4; Ring, Susan M4; Sebert, Sylvain P4; Sengpiel, Verena4; Taal, H Rob4; Watt, Graham C M4; Sattar, Naveed4; Relton, Caroline L4; Jacobsson, Bo5; Frayling, Timothy M4; Sørensen, Thorkild I A6; Murray, Jeffrey C4; Lawlor, Debbie A4; Pennell, Craig E4; Jaddoe, Vincent W V4; Hypponen, Elina4; Lowe, William L4; Jarvelin, Marjo-Riitta4; Davey Smith, George4; Freathy, Rachel M4
1 Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet2 Section for Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet3 Department of Public Health, Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet4 unknown5 Klinisk Epidemiologisk Afdeling6 Section for Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet
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.
Human Molecular Genetics, 2012, Vol 21, Issue 24, p. 5344-58