Dataset Information

Determining the causes and consequences of nicotine dependence: emerging genetic research methods.

ABSTRACT: Tobacco use remains the leading cause of preventable death worldwide. Establishing the genetic aetiology of tobacco use and dependence is an important first step in understanding the neurobiological mechanisms of tobacco use, and in turn the development of effective treatments. In addition, whilst the effects of tobacco use on a broad range of physical illnesses (e.g. lung cancer, respiratory disease, cardiovascular disease) are now well-established, the causal effects of tobacco use on a number of other outcomes remains to be established. Determining the causes and consequences of tobacco use therefore continues to be both a scientific and a public health priority. Here we review emerging methods in genetic research that allow stronger causal inferences to be drawn from observational data.

SUBMITTER: Ware JJ

PROVIDER: S-EPMC4959570 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Determining the causes and consequences of nicotine dependence: emerging genetic research methods.

Ware Jennifer J JJ Munafò Marcus R MR

Current psychiatry reports 20141001 10

Tobacco use remains the leading cause of preventable death worldwide. Establishing the genetic aetiology of tobacco use and dependence is an important first step in understanding the neurobiological mechanisms of tobacco use, and in turn the development of effective treatments. In addition, whilst the effects of tobacco use on a broad range of physical illnesses (e.g. lung cancer, respiratory disease, cardiovascular disease) are now well-established, the causal effects of tobacco use on a number ...[more]

PMID: 25135777

Similar Datasets

Project description:Technological advances have led to the discovery of genetic variants that contribute to many illnesses including nicotine dependence. A multi-stage model of the development of nicotine dependence underlies these genetic studies, and it includes a progression through several stages of smoking behavior from never smoking to nicotine dependence. The final step in this model of dependence is the progression from established smoking behavior to the development of nicotine dependence. Contrasting individuals who smoke only a few cigarettes per day, or "chippers", to heavy smoking, nicotine dependent subjects, focuses a genetic study on the transition from smoking to nicotine dependence. This approach has identified distinct genetic variants that contribute to nicotine dependence on chromosome 15 in the region of the alpha5-alpha3-beta4 family of nicotinic receptor genes. This region of association includes an amino acid change in the alpha5 nicotinic receptor protein, which is most likely a biological variant altering the risk of developing dependence. There is also evidence that other variants alter alpha5 nicotinic receptor gene expression and potentially the risk of smoking. The discovery of these genetic variants and their contribution to the development of nicotine dependence highlight some of the many challenges in genetic studies. The first is that the prevalence of risk alleles can vary across populations so that a genetic risk factor can have a larger or small effect in a population depending on its frequency. The second challenge is that the risk that each genetic variant contributes in the development of a disorder is small and so it is many genes along with environmental risk factors that contribute to the development of a disorder. Interestingly, recent genetic studies of lung cancer and chronic obstructive pulmonary disease demonstrate that this same region has an important genetic influence on these disorders. Finally, there are differences in the risk of developing nicotine dependence based on gender and socioeconomic status. As our understanding of the genetic contributions of nicotine dependence increases, we may improve and personalize our treatments for smoking cessation and enhance our knowledge of other smoking related diseases in those who are at high risk for the many adverse consequences of smoking.

Project description:BackgroundWhile the heritability of cigarette smoking and nicotine dependence (ND) is well-documented, the contribution of specific genetic variants to specific phenotypes has not been closely examined. The objectives of this study were to test the associations between 321 tagging single-nucleotide polymorphisms (SNPs) that capture common genetic variation in 24 genes, and early smoking and ND phenotypes in novice adolescent smokers, and to assess if genetic predictors differ across these phenotypes.MethodsIn a prospective study of 1294 adolescents aged 12-13 years recruited from ten Montreal-area secondary schools, 544 participants who had smoked at least once during the 7-8 year follow-up provided DNA. 321 single-nucleotide polymorphisms (SNPs) in 24 candidate genes were tested for an association with number of cigarettes smoked in the past 3 months, and with five ND phenotypes (a modified version of the Fagerstrom Tolerance Questionnaire, the ICD-10 and three clusters of ND symptoms representing withdrawal symptoms, use of nicotine for self-medication, and a general ND/craving symptom indicator).ResultsThe pattern of SNP-gene associations differed across phenotypes. Sixteen SNPs in seven genes (ANKK1, CHRNA7, DDC, DRD2, COMT, OPRM1, SLC6A3 (also known as DAT1)) were associated with at least one phenotype with a p-value <0.01 using linear mixed models. After permutation and FDR adjustment, none of the associations remained statistically significant, although the p-values for the association between rs557748 in OPRM1 and the ND/craving and self-medication phenotypes were both 0.076.ConclusionsBecause the genetic predictors differ, specific cigarette smoking and ND phenotypes should be distinguished in genetic studies in adolescents. Fifteen of the 16 top-ranked SNPs identified in this study were from loci involved in dopaminergic pathways (ANKK1/DRD2, DDC, COMT, OPRM1, and SLC6A3).ImpactDopaminergic pathways may be salient during early smoking and the development of ND.

Dataset Information

Determining the causes and consequences of nicotine dependence: emerging genetic research methods.

Publications

Determining the causes and consequences of nicotine dependence: emerging genetic research methods.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets