Human Molecular Genetics Advance Access originally published online on May 9, 2009
Human Molecular Genetics 2009 18(15):2922-2927; doi:10.1093/hmg/ddp216
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A common genetic variant in the 15q24 nicotinic acetylcholine receptor gene cluster (CHRNA5–CHRNA3–CHRNB4) is associated with a reduced ability of women to quit smoking in pregnancy
1 Genetics of Complex Traits, Peninsula Medical School, Institute of Biomedical and Clinical Science, Magdalen Road, Exeter EX1 2LU, UK 2 Department of Social Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK 3 Peninsula National Institute for Health Research Clinical Research Facility, Peninsula Medical School, Barrack Road, Exeter EX2 5DW, UK 4 MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK
* To whom correspondence should be addressed. Tel: +44 1392406806; Fax: +44 1392406767; Email: andrew.hattersley{at}pms.ac.uk
Received March 1, 2009; Accepted May 5, 2009
Maternal smoking during pregnancy is associated with low birth weight and adverse pregnancy outcomes. Women are more likely to quit smoking during pregnancy than at any other time in their lives, but some pregnant women continue to smoke. A recent genome-wide association study demonstrated an association between a common polymorphism (rs1051730) in the nicotinic acetylcholine receptor gene cluster (CHRNA5–CHRNA3–CHRNB4) and both smoking quantity and nicotine dependence. We aimed to test whether the same polymorphism that predisposes to greater cigarette consumption would also reduce the likelihood of smoking cessation in pregnancy. We studied 7845 pregnant women of European descent from the South-West of England. Using 2474 women who smoked regularly immediately pre-pregnancy, we analysed the association between the rs1051730 risk allele and both smoking cessation during pregnancy and smoking quantity. Each additional copy of the risk allele was associated with a 1.27-fold higher odds (95% CI 1.11–1.45) of continued smoking during pregnancy (P = 0.0006). Adjustment for pre-pregnancy smoking quantity weakened, but did not remove this association [odds ratio (OR) 1.20 (95% CI 1.03–1.39); P = 0.018]. The same risk allele was also associated with heavier smoking before pregnancy and in the first, but not the last, trimester [OR for smoking 10+ cigarettes/day versus 1–9/day in first trimester = 1.30 (95% CI 1.13–1.50); P = 0.0003]. To conclude, we have found strong evidence of association between the rs1051730 variant and an increased likelihood of continued smoking in pregnancy and have confirmed the previously observed association with smoking quantity. Our data support the role of genetic factors in influencing smoking cessation during pregnancy.
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