title: 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.
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): 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.
authors.affiliation: European Centre for Environment and Human Health, University of Exeter, The Knowledge Spa, Truro, UK.
authors.forename: Jessica
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authors.lastname: Tyrrell
authors.forename: Ville
authors.initials: V
authors.lastname: Huikari
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Christie
authors.forename: Alana
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authors.lastname: Cavadino
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authors.lastname: Bakker
authors.forename: Marie-Jo A
authors.initials: MJ
authors.lastname: Brion
authors.forename: Frank
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authors.lastname: Geller
authors.forename: Lavinia
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authors.lastname: Paternoster
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authors.lastname: Myhre
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authors.lastname: Ebrahim
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authors.lastname: Feenstra
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authors.lastname: Hartikainen
authors.forename: Andrew T
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authors.lastname: Hattersley
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authors.lastname: Hofman
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authors.lastname: Kaakinen
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Lowe
authors.forename: Per
authors.initials: P
authors.lastname: Magnus
authors.forename: Alex
authors.initials: A
authors.lastname: McConnachie
authors.forename: Mads
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authors.lastname: Melbye
authors.forename: Jane W Y
authors.initials: JW
authors.lastname: Ng
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Nohr
authors.forename: Chris
authors.initials: C
authors.lastname: Power
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: Sylvain P
authors.initials: SP
authors.lastname: Sebert
authors.forename: Verena
authors.initials: V
authors.lastname: Sengpiel
authors.forename: H Rob
authors.initials: HR
authors.lastname: Taal
authors.forename: Graham C M
authors.initials: GC
authors.lastname: Watt
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Relton
authors.forename: Bo
authors.initials: B
authors.lastname: Jacobsson
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.forename: Craig E
authors.initials: CE
authors.lastname: Pennell
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.forename: Elina
authors.initials: E
authors.lastname: Hypponen
authors.forename: William L
authors.initials: WL
authors.lastname: Lowe
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Jarvelin
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Freathy
mesh_terms: D001724:Birth Weight / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007223:Infant; D009419:Nerve Tissue Proteins / Q000235:genetics; D011247:Pregnancy; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human