Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure.
- Authors
- MunafΓ², Marcus R; Timofeeva, Maria N; Morris, Richard W; Prieto-Merino, David; Sattar, Naveed; Brennan, Paul; Johnstone, Elaine C; Relton, Caroline; Johnson, Paul C D; Walther, Donna; Whincup, Peter H; Casas, Juan P; Uhl, George R; Vineis, Paolo; Padmanabhan, Sandosh; Jefferis, Barbara J; Amuzu, Antoinette; Riboli, Elio; Upton, Mark N; Aveyard, Paul; Ebrahim, Shah; Hingorani, Aroon D; Watt, Graham; Palmer, Tom M; Timpson, Nicholas J; EPIC Study Group; Davey Smith, George
- Year
- 2012
- Journal
- Journal of the National Cancer Institute
- PMID
- 22534784
- DOI
- 10.1093/jnci/djs191
- PMCID
- PMC3352832
BACKGROUND: Two single-nucleotide polymorphisms, rs1051730 and rs16969968, located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q25 locus, are associated with heaviness of smoking, risk for lung cancer, and other smoking-related health outcomes. Previous studies have typically relied on self-reported smoking behavior, which may not fully capture interindividual variation in tobacco exposure. METHODS: We investigated the association of rs1051730 and rs16969968 genotype (referred to as rs1051730-rs16969968, because these are in perfect linkage disequilibrium and interchangeable) with both self-reported daily cigarette consumption and biochemically measured plasma or serum cotinine levels among cigarette smokers. Summary estimates and descriptive statistical data for 12β364 subjects were obtained from six independent studies, and 2932 smokers were included in the analyses. Linear regression was used to calculate the per-allele association of rs1051730-rs16969968 genotype with cigarette consumption and cotinine levels in current smokers for each study. Meta-analysis of per-allele associations was conducted using a random effects method. The likely resulting association between genotype and lung cancer risk was assessed using published data on the association between cotinine levels and lung cancer risk. All statistical tests were two-sided. RESULTS: Pooled per-allele associations showed that current smokers with one or two copies of the rs1051730-rs16969968 risk allele had increased self-reported cigarette consumption (mean increase in unadjusted number of cigarettes per day per allele = 1.0 cigarette, 95% confidence interval [CI] = 0.57 to 1.43 cigarettes, P = 5.22 Γ 10(-6)) and cotinine levels (mean increase in unadjusted cotinine levels per allele = 138.72 nmol/L, 95% CI = 97.91 to 179.53 nmol/L, P = 2.71 Γ 10(-11)). The increase in cotinine levels indicated an increased risk of lung cancer with each additional copy of the rs1051730-rs16969968 risk allele (per-allele odds ratio = 1.31, 95% CI = 1.21 to 1.42). CONCLUSIONS: Our data show a stronger association of rs1051730-rs16969968 genotype with objective measures of tobacco exposure compared with self-reported cigarette consumption. The association of these variants with lung cancer risk is likely to be mediated largely, if not wholly, via tobacco exposure.
Meta-analysis of association of rs1051730βrs16969968 risk allele with cigarette consumption in current smokers. Data from six independent studies contributed to the meta-analysis. Cotinine levels and self-reported cigarette consumption differed in current smoker case subjects (EPIC Case) and control subjects (EPIC Control) in the EPIC study, so they were analyzed separately. In each study, linear regression was used to calculate per-allele association of rs1051730βrs16969968 genotype with daily cigarette consumption. Units represent cigarettes per day. Unadjusted and adjusted (for cotinine levels) analyses are shown. The I2 statistic was used to estimate the percentage of total variation in study estimates resulting from between-study heterogeneity. Individual study regression coefficients were combined using random effects methods. Squares represent per-allele regression coefficients, which represent mean increase in number of cigarettes per day per allele; size of the square represents inverse of the variance of the regression coefficient; horizontal lines represent 95% CIs; diamonds represent summary estimate combining the study-specific estimates using a random effects model; solid vertical line represents a regression coefficient of 0. P for heterogeneity was derived from the Cochran Q test (one-sided). All other statistical tests were two-sided, and statistical significance required a P value of .05 or less. BRHS = British Regional Heart Study; BWHHS = British Womenβs Heart and Health Study; CI = confidence interval; EPIC = European Prospective Investigation into Cancer and Nutrition; PiP = Patch in Practice.
Meta-analysis of association of rs1051730βrs16969968 risk allele with cotinine levels in current smokers. Data from six independent studies contributed to the meta-analysis. Cotinine levels and self-reported cigarette consumption differed in current smoker case subjects (EPIC Case) and control subjects (EPIC Control) in the EPIC study, so they were analyzed separately. In each study, linear regression was used to calculate per-allele association of rs1051730βrs16969968 genotype with cotinine levels. Units represent nmol/L. Unadjusted and adjusted (for cigarette consumption) analyses are shown. The I2 statistic was used to estimate the percentage of total variation in study estimates resulting from between-study heterogeneity. Individual study regression coefficients were combined using random effects methods. Squares represent per allele regression coefficient, which represents mean increase in cotinine levels per allele; size of the square represents inverse of the variance of the regression coefficient; horizontal lines represent 95% CIs; diamonds represent summary estimate combining the study-specific estimates with a random effects model; solid vertical line represents a regression coefficient of 0. P for heterogeneity was derived from the Cochran Q test (one-sided). All other statistical tests were two-sided, and statistical significance required a P value of .05 or less. BRHS = British Regional Heart Study; BWHHS = British Womenβs Heart and Health Study; CI = confidence interval; EPIC = European Prospective Investigation into Cancer and Nutrition; PiP = Patch in Practice.
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| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Estimating Causal Effects on a Disease Progression Trait Using Bivariate Mendelian Randomisation. | Cai S et al. | β | 2025 | β |
| Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking. | He W et al. | β | 2025 | β |
| Consumption of ultra-processed foods could influence the metabolic syndrome odds: A cross-sectional study. | Mehrabani S et al. | β | 2024 | β |
| Exploring the Bidirectional Causal Pathways Between Smoking Behaviors and Headache: A Mendelian Randomization Study. | Lloyd K et al. | β | 2024 | β |
| Nicotinic Receptor Alpha-5 Subunit Gene Polymorphism is Associated With Heavy Smoking Under a Range of Nicotine Dosing Conditions. | Zuo Y et al. | β | 2024 | β |
| Associations between health behaviours, fertility and reproductive outcomes: triangulation of evidence in the Norwegian Mother, Father and Child Cohort Study (MoBa). | Wootton RE et al. | β | 2023 | β |
| Chance, ignorance, and the paradoxes of cancer: Richard Peto on developing preventative strategies under uncertainty. | Davey Smith G et al. | β | 2023 | β |
| Genetics and epidemiology of mutational barcode-defined clonal hematopoiesis. | Stacey SN et al. | β | 2023 | β |
| Proxy gene-by-environment Mendelian randomization study of the association between cigarette smoking during pregnancy and offspring mental health. | Sallis HM et al. | β | 2023 | β |
| AHRR (cg05575921) Methylation Safely Improves Specificity of Lung Cancer Screening Eligibility Criteria: A Cohort Study. | Jacobsen KK et al. | β | 2022 | β |
| Causal relationship from coffee consumption to diseases and mortality: a review of observational and Mendelian randomization studies including cardiometabolic diseases, cancer, gallstones and other diseases. | Nordestgaard AT | β | 2022 | β |
| Epigenome-wide scan identifies differentially methylated regions for lung cancer using pre-diagnostic peripheral blood. | Zhao N et al. | β | 2022 | β |
| Research Review: How to interpret associations between polygenic scores, environmental risks, and phenotypes. | Pingault JB et al. | β | 2022 | β |
| Self-reported and genetically predicted coffee consumption and smoking in dementia: A Mendelian randomization study. | Nordestgaard AT et al. | β | 2022 | β |
| Dissecting polygenic signals from genome-wide association studies on human behaviour. | Abdellaoui A et al. | β | 2021 | β |
| Pharmacogenetics factors influencing smoking cessation success; the importance of nicotine metabolism. | Perez-Paramo YX et al. | β | 2021 | β |
| SNPs within CHRNA5-A3-B4 and CYP2A6/B6, nicotine metabolite concentrations and nicotine dependence treatment success in smokers. | Hubacek JA et al. | β | 2021 | β |
| Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study. | Wootton RE et al. | β | 2020 | β |
| Examining the effect of smoking on suicidal ideation and attempts: triangulation of epidemiological approaches. | Harrison R et al. | β | 2020 | β |
| Exploring the Effects of Cigarette Smoking on Inflammatory Bowel Disease Using Mendelian Randomization. | Jones DP et al. | β | 2020 | β |
| Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals. | Xu K et al. | β | 2020 | β |
| Proxy gene-by-environment Mendelian randomization study confirms a causal effect of maternal smoking on offspring birthweight, but little evidence of long-term influences on offspring health. | Yang Q et al. | β | 2020 | β |
| Translational Molecular Approaches in Substance Abuse Research. | Fulton SL et al. | β | 2020 | β |
| Appraising the causal relevance of DNA methylation for risk of lung cancer. | Battram T et al. | β | 2019 | 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 |
| Exploration of the role of <i>CHRNA5-A3-B4</i> genotype in smoking behaviours | Lassi G et al. | β | 2019 | β |
| Genome-wide association study in Finnish twins highlights the connection between nicotine addiction and neurotrophin signaling pathway. | HΓ€llfors J et al. | β | 2019 | β |
| Global Epidemiology of Lung Cancer. | Barta JA et al. | β | 2019 | β |
| Polymorphisms of CHRNA3 and CHRNA5: Head and neck cancer and cigarette consumption intensity in a Brazilian population. | Silva MR et al. | β | 2019 | β |
| Smoking and Increased White and Red Blood Cells. | Pedersen KM et al. | β | 2019 | β |
| Smoking, Systemic Inflammation, and Airflow Limitation: A Mendelian Randomization Analysis of 98Β 085 Individuals From the General Population. | Γolak Y et al. | β | 2019 | β |
| The effect of smoking intensity on all-cause and cause-specific mortality-a Mendelian randomization analysis. | Vie GΓ et al. | β | 2019 | β |
| Tobacco Smoking: Risk to Develop Addiction, Chronic Obstructive Pulmonary Disease, and Lung Cancer. | Santoro A et al. | β | 2019 | β |
| Association of Combined Patterns of Tobacco and Cannabis Use in Adolescence With Psychotic Experiences. | Jones HJ et al. | β | 2018 | β |
| CHRNA5 and CHRNA3 polymorphism and lung cancer susceptibility in Palestinian population. | Ayesh BM et al. | β | 2018 | β |
| Genetic polymorphisms associated with smoking behaviour predict the risk of surgery in patients with Crohn's disease. | Lang BM et al. | β | 2018 | β |
| Genetics of biologically based psychological differences. | Sallis H et al. | β | 2018 | β |
| Human Genetics of Addiction: New Insights and Future Directions. | Hancock DB et al. | β | 2018 | β |
| Is smoking heaviness causally associated with alcohol use? A Mendelian randomization study in four European cohorts. | Taylor M et al. | β | 2018 | β |
| Pleiotropy-robust Mendelian randomization. | van Kippersluis H et al. | β | 2018 | β |
| The causal role of smoking on the risk of headache. A Mendelian randomization analysis in the HUNT study. | Johnsen MB 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 |
| Using genetic data to strengthen causal inference in observational research. | Pingault JB et al. | β | 2018 | β |
| A Novel Tobacco Use Phenotype Suggests the 15q25 and 19q13 Loci May be Differentially Associated With Cigarettes per Day and Tobacco-Related Problems. | Richmond-Rakerd LS et al. | β | 2017 | β |
| Genetic epidemiology and Mendelian randomization for informing disease therapeutics: Conceptual and methodological challenges. | Paternoster L et al. | β | 2017 | β |
| Heavier smoking increases coffee consumption: findings from a Mendelian randomization analysis. | BjΓΈrngaard JH et al. | β | 2017 | β |
| <i>AHRR</i> (cg05575921) hypomethylation marks smoking behaviour, morbidity and mortality. | Bojesen SE et al. | β | 2017 | β |
| Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium. | Skaaby T et al. | β | 2017 | β |
| Lung cancer, genetic predisposition and smoking: the Nordic Twin Study of Cancer. | Hjelmborg J et al. | β | 2017 | β |
| Pharmacogenetic Optimization of Smoking Cessation Treatment. | Chenoweth MJ et al. | β | 2017 | β |
| Pharmacotherapy for smoking cessation: effects by subgroup defined by genetically informed biomarkers. | Schuit E et al. | β | 2017 | β |
| The causal role of smoking on the risk of hip or knee replacement due to primary osteoarthritis: a Mendelian randomisation analysis of the HUNT study. | Johnsen MB et al. | β | 2017 | β |
| Uncovering the transcriptomic and epigenomic landscape of nicotinic receptor genes in non-neuronal tissues. | Zhang B 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 |
| Association Between CHRNA3 and CHRNA5 Nicotine Receptor Subunit Gene Variants and Nicotine Dependence in an Isolated Populationof Kashubians in Poland. | Kita-Milczarska K et al. | β | 2016 | β |
| Being overweight in early adulthood is associated with increased mortality in middle age. | Carslake D et al. | β | 2016 | β |
| Best (but oft-forgotten) practices: the design, analysis, and interpretation of Mendelian randomization studies. | Haycock PC et al. | β | 2016 | β |
| Causal Inference in Developmental Origins of Health and Disease (DOHaD) Research. | Gage SH et al. | β | 2016 | β |
| Causal inference-so much more than statistics. | Pearce N et al. | β | 2016 | β |
| Causation, mediation and explanation. | Pearce N et al. | β | 2016 | β |
| CHRNA5/CHRNA3 Locus Associates with Increased Mortality among Smokers. | Kupiainen H et al. | β | 2016 | β |
| Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma. | Naka T 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 |
| Genome-Wide Meta-Analysis of Cotinine Levels in Cigarette Smokers Identifies Locus at 4q13.2. | Ware JJ et al. | β | 2016 | β |
| G = E: What GWAS Can Tell Us about the Environment. | Gage SH et al. | β | 2016 | β |
| High body mass index and cancer risk-a Mendelian randomisation study. | Benn 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 |
| Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans. | Olfson E et al. | β | 2016 | β |
| Schizophrenia and neighbourhood deprivation. | Gage SH et al. | β | 2016 | β |
| Snus use and risk of schizophrenia and non-affective psychosis. | MunafΓ² MR et al. | β | 2016 | β |
| The CHRNA5-A3-B4 Gene Cluster and Smoking: From Discovery to Therapeutics. | Lassi G et al. | β | 2016 | β |
| Analyzing large-scale samples confirms the association between the rs1051730 polymorphism and lung cancer susceptibility. | Han Z et al. | β | 2015 | β |
| A preliminary exploration of college smokers' reactions to nicotine dependence genetic susceptibility feedback. | Lipkus IM 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 |
| Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomization Meta-Analysis in the CARTA Consortium. | Linneberg A 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 |
| Gene promoter methylation and DNA repair capacity in monozygotic twins with discordant smoking habits. | Ottini L et al. | β | 2015 | β |
| Genetic risks to nicotine dependence predict negative mood and affect in current non-smokers. | Chen X et al. | β | 2015 | β |
| Genetics of smoking behaviour. | Ware JJ et al. | β | 2015 | β |
| Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence. | Hancock DB et al. | β | 2015 | β |
| Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium. | Morris RW 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 |
| Mendelian Randomization: New Applications in the Coming Age of Hypothesis-Free Causality. | Evans DM et al. | β | 2015 | β |
| Nicotinic receptor contributions to smoking: insights from human studies and animal models. | Brunzell DH 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 |
| Pharmacogenetics of nicotine and associated smoking behaviors. | Tanner JA et al. | β | 2015 | β |
| Rethinking the association between smoking and schizophrenia. | Gage SH et al. | β | 2015 | β |
| The association of rs1051730 genotype on adherence to and consumption of prescribed nicotine replacement therapy dose during a smoking cessation attempt. | Ware JJ et al. | β | 2015 | β |
| The SNP rs931794 in 15q25.1 Is Associated with Lung Cancer Risk: A Hospital-Based Case-Control Study and Meta-Analysis. | Wang Q et al. | β | 2015 | β |
| Tobacco smoking is causally associated with antipsychotic medication use and schizophrenia, but not with antidepressant medication use or depression. | Wium-Andersen MK et al. | β | 2015 | β |
| Total Exposure Study Analysis consortium: a cross-sectional study of tobacco exposures. | Bergen AW et al. | β | 2015 | β |
| A glimpse into the future - Personalized medicine for smoking cessation. | Bierut LJ et al. | β | 2014 | β |
| A recall-by-genotype study of CHRNA5-A3-B4 genotype, cotinine and smoking topography: study protocol. | Ware JJ et al. | β | 2014 | β |
| Assessing the utility of intermediate phenotypes for genetic mapping of psychiatric disease. | Flint J 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 |
| Beyond cigarettes per day. A genome-wide association study of the biomarker carbon monoxide. | Bloom AJ et al. | β | 2014 | β |
| Causal associations of tobacco smoking with cardiovascular risk factors: a Mendelian randomization analysis of the HUNT Study in Norway. | Γ svold BO et al. | β | 2014 | β |
| Curious cases: Altered dose-response relationships in addiction genetics. | Uhl GR et al. | β | 2014 | β |
| Determining the causes and consequences of nicotine dependence: emerging genetic research methods. | Ware JJ et al. | β | 2014 | β |
| Finding genomic function for genetic associations in nicotine addiction research: the ENCODE project's role in future pharmacogenomic analysis. | Vandenbergh DJ et al. | β | 2014 | β |
| Genetics and smoking. | Loukola A et al. | β | 2014 | β |
| Genetics of alcoholism. | Edenberg HJ et al. | β | 2014 | β |
| Genome-wide association study of smoking behaviours among Bangladeshi adults. | Argos M et al. | β | 2014 | β |
| Genome-wide association study on detailed profiles of smoking behavior and nicotine dependence in a twin sample. | Loukola A et al. | β | 2014 | β |
| High tobacco consumption is causally associated with increased all-cause mortality in a general population sample of 55,568 individuals, but not with short telomeres: a Mendelian randomization study. | Rode L 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 |
| Metabolites of tobacco smoking and colorectal cancer risk. | Cross AJ et al. | β | 2014 | β |
| Phenotype refinement strengthens the association of AHR and CYP1A1 genotype with caffeine consumption. | McMahon G et al. | β | 2014 | β |
| Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers. | Taylor AE et al. | β | 2014 | β |
| The genetic architecture of psychophysiological phenotypes. | MunafΓ² MR et al. | β | 2014 | β |
| Variation in the Ξ± 5 nicotinic acetylcholine receptor subunit gene predicts cigarette smoking intensity as a function of nicotine content. | Macqueen DA 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 |
| CHRNA5-A3-B4 genetic variants alter nicotine intake and interact with tobacco use to influence body weight in Alaska Native tobacco users. | Zhu AZ et al. | β | 2013 | β |
| Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility. | Siedlinski M et al. | β | 2013 | β |
| Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking. | Shenker NS et al. | β | 2013 | β |
| Functional characterization of SNPs in CHRNA3/B4 intergenic region associated with drug behaviors. | Flora AV et al. | β | 2013 | β |
| Genetics. Herit-ability. | Flint J et al. | β | 2013 | β |
| High expression of CHRNA1 is associated with reduced survival in early stage lung adenocarcinoma after complete resection. | Chang PM et al. | β | 2013 | β |
| Substance use disorders: a theory-driven approach to the integration of genetics and neuroimaging. | Karoly HC et al. | β | 2013 | β |
| The ability of plasma cotinine to predict nicotine and carcinogen exposure is altered by differences in CYP2A6: the influence of genetics, race, and sex. | Zhu AZ 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 effect of nicotine on sensorimotor gating is modulated by a CHRNA3 polymorphism. | Petrovsky N et al. | β | 2013 | β |
| Update in lung cancer and mesothelioma 2012. | Powell CA et al. | β | 2013 | β |
| Using Mendelian randomisation to infer causality in depression and anxiety research. | Gage SH et al. | β | 2013 | β |
| Cotinine conundrum--a step forward but questions remain. | Spitz MR et al. | β | 2012 | β |
| From men to mice: CHRNA5/CHRNA3, smoking behavior and disease. | Ware JJ et al. | β | 2012 | β |
| Genetic association analysis of complex diseases incorporating intermediate phenotype information. | Li Y 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 |
| Method for evaluating multiple mediators: mediating effects of smoking and COPD on the association between the CHRNA5-A3 variant and lung cancer risk. | Wang J et al. | β | 2012 | β |
| Twins and the mystery of missing heritability: the contribution of gene-environment interactions. | Kaprio J | β | 2012 | β |