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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

Lookup NU author(s): Dr Kate Potter, Dr Jane Ng, Professor Caroline Relton


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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): 436 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: 4to 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.

Publication metadata

Author(s): Tyrrell J, Huikari V, Christie JT, Cavadino A, Bakker R, Brion MJA, Geller F, Paternoster L, Myhre R, Potter C, Johnson PCD, Ebrahim S, Feenstra B, Hartikainen AL, Hattersley AT, Hofman A, Kaakinen M, Lowe LP, Magnus P, McConnachie A, Melbye M, Ng JWY, Nohr EA, Power C, Ring SM, Sebert SP, Sengpiel V, Taal HR, Watt GCM, Sattar N, Relton CL, Jacobsson B, Frayling TM, Srensen TIA, Murray JC, Lawlor DA, Pennell CE, Jaddoe VWV, Hypponen E, Lowe WL, Jarvelin MR, Smith GD, Freathy RM, Early Growth Genetics EGG

Publication type: Article

Publication status: Published

Journal: Human Molecular Genetics

Year: 2012

Volume: 21

Issue: 24

Pages: 5344-5358

Print publication date: 05/09/2012

ISSN (print): 0964-6906

ISSN (electronic): 1460-2083

Publisher: Oxford University Press


DOI: 10.1093/hmg/dds372


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Funder referenceFunder name
Academy of Finland (SALVE)
Augustinus Foundation
Danish Pharmacists' Fund
Darlington Trust
Egmont Foundation
ENGAGE project
Erasmus University Rotterdam
European Centre for the Environment and Human Health (part of the Peninsula College of Medicine and Dentistry)
European Regional Development Fund (ERDF)
European Social Fund (ESF) Convergence Programme for Cornwall
Jane and Dan Olsson Research Foundation, Gothenburg, Sweden
Medical Research Council (SALVE/PrevMedsyn)
MRC Centre of Epidemiology for Child Health
NHS Cardiovascular Research and Development Programme
Norwegian Ministry of Health
Peninsula National Institute of Health Research (NIHR) Clinical Research Facility at the University of Exeter
Raine Medical Research Foundation
Telethon Institute for Child Health Research
UK Medical Research Council
University Hospital Oulu
University of British Columbia
UWA Faculty of Medicine, Dentistry and Health Sciences
Academy of Finland (Center of Excellence in Complex Disease Genetics)
American Diabetes Association
Australian National Health and Medical Research Council
British Heart Foundation
Curtin University
Danish National Research Foundation
Department of Health (England)
Exeter NHS Research and Development
Health Fund of the Danish Health Insurance Societies
Higher Education Funding Council for England
Isles of Scilly
Juvenile Diabetes Research Foundation International (JDRF)
March of Dimes Birth Defects Foundation
Ministry of Education and Research
National Institute for Health Research
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases, National Human Genome Research Institute, National Institute of Child Health and Human Development
National Institute of Diabetes, Digestive, and Kidney Diseases
Sahlgrenska University Hospital, Sahlgrenska Academy, Gothenburg, Sweden
South West NHS Research and Development
University of Bristol
University of Western Australia (UWA)
Women and Infants Research Foundation
01 AK 803 A-HGerman Bundesministerium fuer Forschung und Technology
01 IG 07015 GGerman Bundesministerium fuer Forschung und Technology
068545/Z/02Wellcome Trust
085515Wellcome Trust
085541/Z/08/ZWellcome Trust
092731Wellcome Trust
1 UO1 NS 047537-01NIH/NINDS
129418Academy of Finland
104781Academy of Finland
151918/S10Norwegian Research Council/FUGE
183220/S10Norwegian Research Council/FUGE
120315Academy of Finland
2008-21198Swedish Medical Society, Stockholm, Sweden
75617Biocenter, University of Oulu, Finland
C08.2251Dutch Kidney Foundation
916.10159Netherlands Organization for Health Research and Development
ALFGBG-136431Swedish government
G0500539Medical Research Council, UK
FUGE 183220/S10Norwegian Research Council, Oslo, Norway
G0000934Medical Research Council
G0600705Medical Research Council, UK
M01-RR00048National Center for Research Resources
M01-RR00080National Center for Research Resources
MRC G0601653Medical Research Council
QLG1-CT-2000-01643European Commission (EURO-BLCS)
R01-HD34242Eunice Kennedy Shriver National Institute of Child Health and Human Development
R01-HD34243Eunice Kennedy Shriver National Institute of Child Health and Human Development
RD08/0003692Diabetes UK
U01 DK062418
U01 HG004415National Human Genome Research Institute
ZonMw 21000074Netherlands Organization for Health Research and Development
U01HG004423US National Institutes of Health (NIH) Genes, Environment and Health Initiative (GEI)
U01HG004438NIH GEI
WT 084762MAWellcome Trust
WT084762Wellcome Trust
ZonMw 90700303Netherlands Organization for Health Research and Development