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.
paper
Cited
Public
- Authors
- Freathy, Rachel M; Ring, Susan M; Shields, Beverley; Galobardes, Bruna; Knight, Beatrice; Weedon, Michael N; Smith, George Davey; Frayling, Timothy M; Hattersley, Andrew T
- Year
- 2009
- Journal
- Human molecular genetics
- PMID
- 19429911
- DOI
- 10.1093/hmg/ddp216
- PMCID
- PMC2706684
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.
No figures extracted from this document.
1β20 of 26
Next β
| Name | Type |
|---|---|
| 1649 mothers local | cohort |
| adoptive families cohort local | cohort |
| age | phenotype |
| Age started smoking local | phenotype |
| ALSPAC | cohort |
| Avon Longitudinal Study of Parents and Children (ALSPAC) | cohort |
| birth weight | phenotype |
| BMI | phenotype |
| Chrna3 | gene |
| CHRNA5 | gene |
| CHRNA5-CHRNA3-CHRNB4 cluster | gene |
| Chrnb4 | gene |
| cigarettes | phenotype |
| common variants | cohort |
| continued smoking local | phenotype |
| continued smoking in pregnancy local | phenotype |
| continuing to smoke in pregnancy local | phenotype |
| cotinine | drug |
| educational attainment | phenotype |
| EFSOCH local | cohort |
| Europeans | cohort |
| European women local | cohort |
| Exeter Family Study of Childhood Health local | cohort |
| Fetal growth restriction local | phenotype |
| first trimester smoking local | phenotype |
| first trimester smoking quantity local | phenotype |
| FTO | gene |
| FTO common variant | variant |
| heavy smoking | phenotype |
| light smokers | phenotype |
| low birth weight | phenotype |
| lung cancer | phenotype |
| maternal age | phenotype |
| maternal genotype local | variant |
| maternal risk allele local | variant |
| maternal smoking | phenotype |
| metabolic traits | phenotype |
| nicotine | drug |
| nicotine dependence | phenotype |
| nicotinic agonist | drug |
| Non-responders | phenotype |
| non-smokers | phenotype |
| nonβsmoking women local | cohort |
| obesity | phenotype |
| Occupational position local | phenotype |
| parity | phenotype |
| partner's smoking local | phenotype |
| Partner's smoking status local | phenotype |
| pregnancy | phenotype |
| pregnancy complications | phenotype |
| pregnant women | cohort |
| Pre-pregnancy smokers local | phenotype |
| pre-pregnancy smoking quantity local | phenotype |
| preterm birth | phenotype |
| Responders | phenotype |
| risk allele | cohort |
| rs1051730 | variant |
| rs16969968 | variant |
| smoking | phenotype |
| smoking behaviour | phenotype |
| smoking cessation | phenotype |
| smoking cessation in pregnancy local | phenotype |
| Smoking cessation in pregnancy local | phenotype |
| smoking mothers (first/third trimester) local | cohort |
| smoking prevalence | phenotype |
| smoking quantity | phenotype |
| smoking quantity before pregnancy local | phenotype |
| smoking quantity in first trimester local | phenotype |
| socioeconomic position local | phenotype |
| stopped smoking local | phenotype |
| Sweden | cohort |
| Third trimester local | phenotype |
| third trimester smokers local | cohort |
| third trimester smoking local | phenotype |
| third trimester smoking quantity local | phenotype |
| Townsend deprivation score local | phenotype |
| United Kingdom | cohort |
| USA | cohort |
No uploaded files.
Not in any collection.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Biochemical Diagnosis in Substance and Non-substance Addiction. | Shen W et al. | β | 2025 | β |
| Exploring and Accounting for Genetically Driven Effect Heterogeneity in Mendelian Randomization. | Jaitner A et al. | β | 2025 | β |
| Relationship between tobacco smoking and metabolic syndrome: a Mendelian randomization analysis. | Lin CC et al. | β | 2025 | β |
| Addressing causal relationship between drinking behavior and metabolic syndrome: one-sample Mendelian randomization analysis. | Yang CW et al. | β | 2024 | β |
| A multi-ancestry cerebral cortex transcriptome-wide association study identifies genes associated with smoking behaviors. | Tan Q et al. | β | 2024 | β |
| Smoking during pregnancy and its effect on placental weight: a Mendelian randomization study. | Jaitner A et al. | β | 2024 | β |
| CHRNA5-A3-B4 and DRD2 Genes and Smoking Cessation Throughout Adulthood: A Longitudinal Study of Women. | Jones SK et al. | β | 2023 | β |
| Genetic Associations with Smoking Relapse and Proportion of Follow-up in Smoking Relapse throughout Adulthood in Pre- and Postmenopausal Women. | Jones SK et al. | β | 2023 | β |
| A systematic review of genetic variation within nicotinic acetylcholine receptor genes and cigarette smoking cessation. | Jones SK et al. | β | 2022 | β |
| Efficient estimation of indirect effects in case-control studies using a unified likelihood framework. | Satten GA et al. | β | 2022 | β |
| <i>CHRNA5</i> rs16969968 and <i>CHRNA3</i> rs578776 polymorphisms are associated with multiple nicotine dependence phenotypes in Bangladeshi smokers. | Chaity NI et al. | β | 2022 | β |
| The potential of DNA methylation as a biomarker for obesity and smoking. | Heikkinen A et al. | β | 2022 | β |
| The translational challenges of precision oncology. | Pich O et al. | β | 2022 | β |
| Efficient Estimation of Indirect Effects in Case-Control Studies Using a Unified Likelihood Framework | Satten GA et al. | β | 2021 | β |
| Multidimensional Intersection of Nicotine, Gene Expression, and Behavior. | Sherafat Y et al. | β | 2021 | β |
| Nicotinic acetylcholine gene cluster CHRNA5-A3-B4 variants influence smoking status in a Bangladeshi population. | Chaity NI et al. | β | 2021 | β |
| The Intergenerational Transmission of Developmental Nicotine Exposure-Induced Neurodevelopmental Disorder-Like Phenotypes is Modulated by the Chrna5 D397N Polymorphism in Adolescent Mice. | Buck JM et al. | β | 2021 | β |
| Nicotinic acetylcholine receptors and nicotine addiction: A brief introduction. | Wittenberg RE et al. | β | 2020 | β |
| Association Between rs1051730 and Smoking During Pregnancy in Dutch Women. | Mbarek H et al. | β | 2019 | β |
| Associations of maternal quitting, reducing, and continuing smoking during pregnancy with longitudinal fetal growth: Findings from Mendelian randomization and parental negative control studies. | Brand JS et al. | β | 2019 | β |
| Chronic Obstructive Pulmonary Disease Risk and Smoking Cessation Changes Induced by <i>CHRNA5-A3</i> and <i>CHRNB3-A6</i> Variation in a Chinese Male Population. | Zhao L et al. | β | 2019 | β |
| Using genomic profiling for understanding and improving response to smoking cessation treatment. | Bierut LJ | β | 2019 | β |
| Cholinergic receptor nicotinic alpha 5 subunit polymorphisms are associated with smoking cessation success in women. | Tomaz PRX et al. | β | 2018 | β |
| Maternal smoking during pregnancy and autism: using causal inference methods in a birth cohort study. | Caramaschi D et al. | β | 2018 | β |
| Pathways to precision medicine in smoking cessation treatments. | Chen LS et al. | β | 2018 | β |
| Preparing the Way: Exploiting Genomic Medicine to Stop Smoking. | Bierut LJ et al. | β | 2018 | β |
| The interaction of the Chrna5 D398N variant with developmental nicotine exposure. | O'Neill HC et al. | β | 2018 | β |
| The role of nicotinic receptor genes (CHRN) in the pathways of prenatal tobacco exposure on smoking behavior among young adult light smokers. | Selya AS et al. | β | 2018 | β |
| The Value of Biosamples in Smoking Cessation Trials: A Review of Genetic, Metabolomic, and Epigenetic Findings. | Saccone NL et al. | β | 2018 | β |
| Toward the implementation of genomic applications for smoking cessation and smoking-related diseases. | Ramsey AT et al. | β | 2018 | β |
| Biochemical Diagnosis in Substance and Non-substance Addiction. | Shen W et al. | β | 2017 | β |
| Early Life Exposures and Adult Cancer Risk. | Clarke MA et al. | β | 2017 | β |
| Evaluation of a Novel Difficulty of Smoking Cessation Phenotype Based on Number of Quit Attempts. | Stevens VL et al. | β | 2017 | β |
| Genome-wide association studies of cancer: current insights and future perspectives. | Sud A et al. | β | 2017 | β |
| Pharmacotherapy for smoking cessation: effects by subgroup defined by genetically informed biomarkers. | Schuit E et al. | β | 2017 | β |
| Using Mendelian randomization to determine causal effects of maternal pregnancy (intrauterine) exposures on offspring outcomes: Sources of bias and methods for assessing them. | Lawlor D et al. | β | 2017 | β |
| Causal Inference in Developmental Origins of Health and Disease (DOHaD) Research. | Gage SH et al. | β | 2016 | β |
| CHRNA5/CHRNA3 Locus Associates with Increased Mortality among Smokers. | Kupiainen H et al. | β | 2016 | β |
| Contribution of Variants in CHRNA5/A3/B4 Gene Cluster on Chromosome 15 to Tobacco Smoking: From Genetic Association to Mechanism. | Wen L et al. | β | 2016 | β |
| Converging findings from linkage and association analyses on susceptibility genes for smoking and other addictions. | Yang J et al. | β | 2016 | β |
| High Prevalence of Smoking in the Roma Population Seems to Have No Genetic Background. | Fiatal S et al. | β | 2016 | β |
| How can we Improve on Modeling Nicotine Addiction to Develop Better Smoking Cessation Treatments? | Shoaib M et al. | β | 2016 | β |
| Nicotinic acetylcholine receptors: upregulation, age-related effects and associations with drug use. | Melroy-Greif WE et al. | β | 2016 | β |
| Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence. | Zuo L et al. | β | 2016 | β |
| Testing Causal Effects of Maternal Smoking During Pregnancy on Offspring's Externalizing and Internalizing Behavior. | Dolan CV et al. | β | 2016 | β |
| A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans. | Jensen KP et al. | β | 2015 | β |
| Ancestral experience as a game changer in stress vulnerability and disease outcomes. | Metz GA et al. | β | 2015 | β |
| Association between genetic variants on chromosome 15q25 locus and several nicotine dependence traits in Polish population: a case-control study. | Buczkowski K et al. | β | 2015 | β |
| Candidate gene study for smoking, alcohol use, and body weight in a sample of pregnant women. | Wehby GL et al. | β | 2015 | β |
| CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis--a meta-analysis. | Chen LS et al. | β | 2015 | β |
| Effect of smoking on physical and cognitive capability in later life: a multicohort study using observational and genetic approaches. | North TL et al. | β | 2015 | β |
| Effect of the rs1051730-rs16969968 variant and smoking cessation treatment: a meta-analysis. | Leung T et al. | β | 2015 | β |
| Examination of the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) Factor Structure in a Sample of Pregnant Smokers. | Parrott CE et al. | β | 2015 | β |
| Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation. | Chen LS et al. | β | 2015 | β |
| Lack of Associations of CHRNA5-A3-B4 Genetic Variants with Smoking Cessation Treatment Outcomes in Caucasian Smokers despite Associations with Baseline Smoking. | Tyndale RF et al. | β | 2015 | β |
| Nicotinic receptors in non-human primates: Analysis of genetic and functional conservation with humans. | Shorey-Kendrick LE et al. | β | 2015 | β |
| Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC). | Richmond RC et al. | β | 2015 | β |
| The value of control conditions for evaluating pharmacogenetic effects. | Chen LS et al. | β | 2015 | β |
| ADHD diagnosis may influence the association between polymorphisms in nicotinic acetylcholine receptor genes and tobacco smoking. | Polina ER et al. | β | 2014 | β |
| A glimpse into the future - Personalized medicine for smoking cessation. | Bierut LJ et al. | β | 2014 | β |
| Association of CHRNA5-A3-B4 SNP rs2036527 with smoking cessation therapy response in African-American smokers. | Zhu AZ et al. | β | 2014 | β |
| CHRNA5 variant predicts smoking cessation in patients with acute myocardial infarction. | Chen LS et al. | β | 2014 | β |
| Commentary: Does mortality from smoking have implications for future Mendelian randomization studies? | Taylor AE et al. | β | 2014 | β |
| Interplay of genetic risk (CHRNA5) and environmental risk (partner smoking) on cigarette smoking reduction. | Chen LS et al. | β | 2014 | β |
| Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium. | Taylor AE et al. | β | 2014 | β |
| Maternal smoking during pregnancy and offspring smoking initiation: assessing the role of intrauterine exposure. | Taylor AE et al. | β | 2014 | β |
| Mendelian randomization in health research: using appropriate genetic variants and avoiding biased estimates. | Taylor AE et al. | β | 2014 | β |
| Partner smoking and maternal cotinine during pregnancy: implications for negative control methods. | Taylor AE et al. | β | 2014 | β |
| Variants in two adjacent genes, EGLN2 and CYP2A6, influence smoking behavior related to disease risk via different mechanisms. | Bloom AJ et al. | β | 2014 | β |
| Approaches for strengthening causal inference regarding prenatal risk factors for childhood behavioural and psychiatric disorders. | Lewis SJ et al. | β | 2013 | β |
| Cohort Profile: the Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort. | Fraser A et al. | β | 2013 | β |
| Genetic instrumental variable studies of effects of prenatal risk factors. | Wehby GL et al. | β | 2013 | β |
| Genomics and personalized medicine: <i>CHRNA5-CHRNA3-CHRNB4</i> and smoking cessation treatment. | Chen LS et al. | β | 2013 | β |
| Nicotinic acetylcholine receptor variation and response to smoking cessation therapies. | Bergen AW et al. | β | 2013 | β |
| The causal role of smoking in anxiety and depression: a Mendelian randomization analysis of the HUNT study. | BjΓΈrngaard JH et al. | β | 2013 | β |
| The Ξ±5 subunit regulates the expression and function of Ξ±4*-containing neuronal nicotinic acetylcholine receptors in the ventral-tegmental area. | Chatterjee S et al. | β | 2013 | β |
| Using Mendelian randomisation to infer causality in depression and anxiety research. | Gage SH et al. | β | 2013 | β |
| A common genetic variant at 15q25 modifies the associations of maternal smoking during pregnancy with fetal growth: the generation R study. | Leermakers ET et al. | β | 2012 | β |
| Alpha-5 and -3 nicotinic receptor gene variants predict nicotine dependence but not cessation: findings from the COMMIT cohort. | Bousman CA et al. | β | 2012 | β |
| Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure. | MunafΓ² MR et al. | β | 2012 | β |
| From men to mice: CHRNA5/CHRNA3, smoking behavior and disease. | Ware JJ et al. | β | 2012 | β |
| 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. | Tyrrell J et al. | β | 2012 | β |
| Interplay of genetic risk factors (CHRNA5-CHRNA3-CHRNB4) and cessation treatments in smoking cessation success. | Chen LS et al. | β | 2012 | β |
| Maternal and paternal smoking during pregnancy and risk of ADHD symptoms in offspring: testing for intrauterine effects. | Langley K et al. | β | 2012 | β |
| Parent of origin effects. | Guilmatre A et al. | β | 2012 | β |
| Pharmacogenetics of smoking cessation: role of nicotine target and metabolism genes. | Gold AB et al. | β | 2012 | β |
| Smoking and body weight: evidence using genetic instruments. | Wehby GL et al. | β | 2012 | β |
| Smoking cessation pharmacogenetics: analysis of varenicline and bupropion in placebo-controlled clinical trials. | King DP et al. | β | 2012 | β |
| The CHRNA5-A3-B4 gene cluster in nicotine addiction. | Berrettini WH et al. | β | 2012 | β |
| A genetic instrumental variables analysis of the effects of prenatal smoking on birth weight: evidence from two samples. | Wehby GL et al. | β | 2011 | β |
| A genetic perspective on nutritional profiles: do we still need them? | Gregori D et al. | β | 2011 | β |
| Association of the CHRNA5-A3-B4 gene cluster with heaviness of smoking: a meta-analysis. | Ware JJ et al. | β | 2011 | β |
| CHRNA3 rs1051730 genotype and short-term smoking cessation. | MunafΓ² MR et al. | β | 2011 | β |
| Chromosome 15q25 (CHRNA3-CHRNA5) variation impacts indirectly on lung cancer risk. | Wang Y et al. | β | 2011 | β |
| Dopamine-related genes and spontaneous smoking cessation in ever-heavy smokers. | Breitling LP et al. | β | 2011 | β |
| GENES AS INSTRUMENTS FOR STUDYING RISK BEHAVIOR EFFECTS: AN APPLICATION TO MATERNAL SMOKING AND OROFACIAL CLEFTS. | Wehby G et al. | β | 2011 | β |
| Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index. | Freathy RM et al. | β | 2011 | β |
| Markers in the 15q24 nicotinic receptor subunit gene cluster (CHRNA5-A3-B4) predict severity of nicotine addiction and response to smoking cessation therapy. | Sarginson JE et al. | β | 2011 | β |
| Partial agonists of the Ξ±3Ξ²4* neuronal nicotinic acetylcholine receptor reduce ethanol consumption and seeking in rats. | Chatterjee S et al. | β | 2011 | β |
| Smoking is associated with, but does not cause, depressed mood in pregnancy--a mendelian randomization study. | Lewis SJ et al. | β | 2011 | β |
| TTC12-ANKK1-DRD2 and CHRNA5-CHRNA3-CHRNB4 influence different pathways leading to smoking behavior from adolescence to mid-adulthood. | Ducci F et al. | β | 2011 | β |
| ASCL1 regulates the expression of the CHRNA5/A3/B4 lung cancer susceptibility locus. | Improgo MR et al. | β | 2010 | β |
| Commentary: gene-environment interactions and smoking-related cancers. | Thorgeirsson TE et al. | β | 2010 | β |
| Convergence of genetic findings for nicotine dependence and smoking related diseases with chromosome 15q24-25. | Bierut LJ | β | 2010 | β |
| From smoking to lung cancer: the CHRNA5/A3/B4 connection. | Improgo MR et al. | β | 2010 | β |
| Genetics of addictions. | Hartz SM et al. | β | 2010 | β |
| Genetics of addictions. | Hartz SM et al. | β | 2010 | β |
| Genetic variation in three candidate genes and nicotine dependence, withdrawal and smoking cessation in hospitalized patients. | De Ruyck K et al. | β | 2010 | β |
| Low-moderate prenatal alcohol exposure and risk to child behavioural development: a prospective cohort study. | Robinson M et al. | β | 2010 | β |
| Meta-analysis of 15 genome-wide linkage scans of smoking behavior. | Han S et al. | β | 2010 | β |
| Multiple cholinergic nicotinic receptor genes affect nicotine dependence risk in African and European Americans. | Saccone NL et al. | β | 2010 | β |
| Preclinical data elucidate molecular and neural mechanisms of perinatal nicotine effects on neurodevelopment and behavior: translational opportunities and implications. | Lerman C | β | 2010 | β |
| Resequencing of nicotinic acetylcholine receptor genes and association of common and rare variants with the FagerstrΓΆm test for nicotine dependence. | Wessel J et al. | β | 2010 | β |
| Role of 5p15.33 (TERT-CLPTM1L), 6p21.33 and 15q25.1 (CHRNA5-CHRNA3) variation and lung cancer risk in never-smokers. | Wang Y et al. | β | 2010 | β |
| The impact of smoking in Crohn's disease: no smoke without fire. | Aldhous MC et al. | β | 2010 | β |
| The nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster: dual role in nicotine addiction and lung cancer. | Improgo MR et al. | β | 2010 | β |
| Variation in nicotinic acetylcholine receptor genes is associated with multiple substance dependence phenotypes. | Sherva R et al. | β | 2010 | β |
| A non-synonymous variant in ADH1B is strongly associated with prenatal alcohol use in a European sample of pregnant women. | Zuccolo L et al. | β | 2009 | β |
| Commentary: 'Smoking and lung cancer'--the embryogenesis of modern epidemiology. | Vandenbroucke JP | β | 2009 | β |
| Nicotine dependence and genetic variation in the nicotinic receptors. | Bierut LJ | β | 2009 | β |
| Smoking and lung cancer: causality, Cornfield and an early observational meta-analysis. | Smith GD | β | 2009 | β |