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 language | English (US) |
|---|---|
| Pages (from-to) | 5344-5358 |
| Number of pages | 15 |
| Journal | Human molecular genetics |
| Volume | 21 |
| Issue number | 24 |
| DOIs | |
| State | Published - Dec 2012 |
Funding
HAPO: This study was funded by grants R01-HD34242 and R01-HD34243 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Diabetes, Digestive, and Kidney Diseases, U01 HG004415 from the National Human Genome Research Institute, M01-RR00048 and M01-RR00080 by the National Center for Research Resources and by the American Diabetes Association. Genotyping was funded by Diabetes UK grant RD08/0003692. Researchers were funded by the European Centre for the Environment and Human Health (part of the Peninsula College of Medicine and Dentistry, which is a joint entity of the University of Exeter, the University of Plymouth and the NHS in the southwest) and is supported by investment from the European Regional Development Fund (ERDF) and the European Social Fund (ESF) Convergence Programme for Cornwall and the Isles of Scilly (J.T.); The Dutch Kidney Foundation (C08.2251) (H.R.T.); the Netherlands Organization for Health Research and Development (ZonMw 90700303, 916.10159) (V.W.V.J.); the Higher Education Funding Council for England (C.L.R.); National Institute for Health Research (A.T.H. and C.P.); the University of British Columbia, Clinician Investigator Program (J.W.Y.N.); UK Medical Research Council and University of Bristol (D.A.L. and G.D.S.); Wellcome Trust [WT 084762MA (L.P.), 085541/Z/ 08/Z (R.M.F.) and 085515 (M.-J.A.B.)]. Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust. EFSOCH: The Exeter Family Study of Childhood Health (EFSOCH) was supported by South West NHS Research and Development, Exeter NHS Research and Development, the Darlington Trust and the Peninsula National Institute of Health Research (NIHR) Clinical Research Facility at the University of Exeter. The opinions given in this paper do not necessarily represent those of NIHR, the NHS or the Department of Health. BWHHS: The British Women\u2019s Heart and Health Study (BWHHS) is funded by the Department of Health (England) Policy Research Programme and the British Heart Foundation. Raine: We gratefully acknowledge the Raine Study participants and their families and the Raine Study Team for cohort co-ordination and data collection. We also thank the NHMRC for their long-term contribution to funding the study and the Telethon Institute for Child Health Research for long-term support of the study. Core management for the Raine study is funded by The University of Western Australia (UWA), Telethon Institute for Child Health Research, Raine Medical Research Foundation, UWA Faculty of Medicine, Dentistry and Health Sciences, Curtin University and the Women and Infants Research Foundation. Collection, extraction and geno-typing of maternal and child DNA in Raine was funded by the Australian National Health and Medical Research Council and the Women and Infants Research Foundation. Antenatal data collection was supported by the Raine Medical Research Foundation. DNBC: The DNBC was established with major funding from the Danish National Research Foundation. Additional support for the DNBC has been obtained from the Danish Pharmacists\u2019 Fund, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation and the Health Fund of the Danish Health Insurance Societies. Generation R: The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. We gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives and pharmacies in Rotterdam. The generation and management of GWAS genotype data for the Generation R Study were done at the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Netherlands. We would like to thank Karol Estrada, Dr Tobias A. Knoch, Anis Abuseiris, Luc V. de Zeeuw and Rob de Graaf for their help in creating GRIMP, BigGRID, MediGRID and Services@MediGRID/ D-Grid (funded by the German Bundesministerium fuer For-schung und Technology; grants 01 AK 803 A-H, 01 IG 07015 G) for access to their grid computing resources. We thank Mila Jhamai, Manoushka Ganesh, Pascal Arp, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters for their help in creating, managing and QC of the GWAS database. Also, we thank Karol Estrada and Carolina Medina-Gomez for their support in the creation and analysis of imputed data. The Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development (ZonMw 21000074). DNBC-PTB: The GWAS data for the DNBC study of preterm birth was done within the Gene, Environment Association Studies (GENEVA) consortium, with funding provided through the US National Institutes of Health (NIH) Genes, Environment and Health Initiative (GEI; U01HG004423). Assistance with genotype cleaning and general study coordination for the preterm birth project were provided by the GENEVA Coordinating Center (U01HG004446). Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research, with support from the NIH GEI (U01HG004438). MoBa: The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and the Ministry of Education and Research, NIH/NIEHS (contract no NO-ES-75558), NIH/NINDS (grant no. 1 UO1 NS 047537-01) and the Norwegian Research Council/FUGE (grant no. 151918/S10 and no 183220/S10), Norwegian Research Council, Oslo, Norway (FUGE 183220/S10). Swedish government grants to researchers in public health service (ALF) (ALFGBG-136431), Sahlgrenska University Hospital, Sahlgrenska Academy, Gothenburg, Sweden, Swedish Medical Society, Stockholm, Sweden (2008-21198) and Jane and Dan Olsson Research Foundation, Gothenburg, Sweden. NFBC1966: We thank Professor Paula Rantakallio (launch of NFBC1966 and initial data collection), Ms Sarianna Vaara (data collection), Ms Tuula Ylitalo (administration), Mr Markku Koiranen (data management), Ms Outi Tornwall and Ms Minttu Jussila (DNA biobanking). This work was supported by the Academy of Finland (project grants 104781, 120315, 129418 and Center of Excellence in Complex Disease Genetics and SALVE), University Hospital Oulu, Bio-center, University of Oulu, Finland (75617), the European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643), NHLBI (5R01HL087679-02) through the STAMPEED programme (1RL1MH083268-01), NIH/NIMH (5R01MH63706:02), ENGAGE project and grant agreement (HEALTH-F4-2007-201413) and the Medical Research Council, UK (G0500539, G0600705, Pre-vMetSyn/SALVE). This research used resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the 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 and Juvenile Diabetes Research Foundation International (JDRF) and supported by U01 DK062418. This study makes use of data generated by the Wellcome Trust Case-Control Consortium II (083948). The Medical Research Council provides funds for the MRC Centre of Epidemiology for Child Health. 1958BC_T1DGC and 1958BC_WTCCC2: Dr Sue Ring and Dr Wendy McArdle (University of Bristol) and Mr Jon Johnson (Centre for Longitudinal Studies, Institute of Education, London) are thanked for help with data linkage. The study was supported by the Medical Research Council (MRC G0601653 and SALVE/PrevMedsyn). Collection of DNA in the 1958 Birth Cohort was funded by the MRC grant G0000934 and the Wellcome Trust grant 068545/Z/02. ALSPAC: This publication is the work of the authors, and Rachel Freathy, Debbie Lawlor and George Davey Smith will serve as guarantors for the contents of this paper. The Avon Longitudinal Study of Parents and Children (ALSPAC) has core support provided by the UK Medical Research Council, the Wellcome Trust (grant ref: 092731) and the University of Bristol. DNBC-GOYA: The DNBC-GOYA study was supported by the Wellcome Trust (grant WT084762).
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Genetics(clinical)