Genetic and environmental contributions to smoking

True, William R.; Heath, Andrew C.; Scherrer, Jeffrey F.; Waterman, Brian; Goldberg, Jack; Lin, Nong; Eisen, Seth A.; Lyons, Michael J.; Tsuang, Ming T.

doi:10.1046/j.1360-0443.1997.921012775.x

Cited by 97 publications

(134 citation statements)

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Section: Vulnerability To Addiction and Allostasis: Genetic Contributsupporting

confidence: 75%

“…For example, using multiple logistic regression analyses predicting persistence in smoking among smokers, the odds ratios are significantly higher for monozygotic twins than for dizygotic twins (Heath and Madden 1998). Similar conclusions have been drawn using a genetic liability model approach with monozygotic and dizygotic twins (True et al 1997).One untested hypothesis is that individuals at risk for drug abuse in fact have a biological vulnerability within the same domains as those biological changes hypothesized to develop over the course of heavy drug intake regardless of genetic history (see above). In the study of the genetics of alcoholism, there is evidence of genetic control over various aspects of drinking but to a modest degree for any one dimension.…”

supporting

confidence: 59%

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Drug Addiction, Dysregulation of Reward, and Allostasis

Koob

Moal

2001

Neuropsychopharmacology

2,561

1,962

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This paper reviews recent developments in the neurocircuitry and neurobiology of addiction from a perspective of allostasis. A model is proposed for brain changes that occur during the development of addiction that explain the persistent vulnerability to relapse long after drug-taking has ceased. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in the compulsive use and loss of control over drug-taking. The development of addiction recruits different sources of reinforcement, different neuroadaptive mechanisms, and different neurochemical changes to dysregulate the brain reward system. Counteradaptive processes such as opponent-process that are part of normal homeostatic limitation of reward function fail to return within the normal homeostatic range and are hypothesized to form an allostatic state. Allostasis from the addiction perspective is defined as the process of maintaining apparent reward function stability by changes in brain reward mechanisms. The allostatic state represents a chronic deviation of reward set point and is fueled not only by dysregulation of reward circuits per se, but also by the activation of brain and hormonal stress responses. The manifestation of this allostatic state as compulsive drugtaking and loss of control over drug-taking is hypothesized to be expressed through activation of brain circuits involved in compulsive behavior such as the cortico-striatal-thalamic loop. The view that addiction is the pathology that results from an allostatic mechanism using the circuits established for natural rewards provides a realistic approach to BACKGROUNDDrug addiction is a chronically relapsing disorder that is defined by two major characteristics: a compulsion to take the drug with a narrowing of the behavioral repertoire toward excessive drug intake, and a loss of control in limiting intake (American Psychiatric Association 1994; World Health Organization 1992). An important challenge for neurobiological research is to understand the neuroadaptive differences between controlled drug use and loss of control, and by extension, the molecular, cellular and system processes that lead to addiction (Koob and Le Moal 1997).Animal models are critical for understanding the neuropharmacological mechanisms involved in the development of addiction. While there are no complete animal models of addiction, animal models do exist for many elements of the syndrome. These elements can be derived from symptoms or diagnostic criteria for addiction or conceptual frameworks such as different sources of reinforcement (American Psychiatric Association 1994; World Health Organization 1992). Linking neu- 24 , NO . 2 ropharmacological events to animal models can occur at multiple levels of analysis -molecular, cellular and system -and it will only be the integration of these changes across dimensions of analysis that will allow a full understanding of the neurobiology of drug addiction.Advances in neuroscience research are rapidly unr...

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Section: Vulnerability To Addiction and Allostasis: Genetic Contributsupporting

confidence: 75%

supporting

confidence: 59%

Drug Addiction, Dysregulation of Reward, and Allostasis

Koob

Moal

2001

Neuropsychopharmacology

2,561

1,962

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“…[3][4][5][6] Many twin studies have revealed that there is a strong genetic component in nicotine dependence. [7][8][9][10][11][12][13][14][15][16] Meta-analysis of reported twin studies indicated that genetics accounts for at least 50% of the liability to this disorder. 17,18 Thus, identifying the genes predisposing to nicotine dependence and understanding of its molecular mechanism will be of great interest to effectively prevent or treat it.…”

Section: Introductionmentioning

confidence: 99%

Mapping and verification of susceptibility loci for smoking quantity using permutation linkage analysis

Wang

2005

Pharmacogenomics J

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Nicotine dependence is the most prevalent form of drug addiction in the US and throughout the world. Epidemiological studies demonstrate that genetics accounts for at least 50% of the liability to nicotine dependence. However, there have been very limited linkage studies providing convincing evidence of susceptibility genomic loci for this disorder. In this study, we conducted genome-wide permutation linkage analyses on the smoking data collected between 1970 and 1972 of the Framingham Heart Study (FHS) to account for the abnormality associated with the smoking quantity (defined as the number of cigarettes smoked per day). We used empirical thresholds obtained from permutation tests to determine the significance of each genomic region. The variance component method implemented in SOLAR was used for the analysis. Under the empirical genome-wide thresholds determined specifically for the FHS smoking data, we found two highly or near-highly significant linkages of nicotine dependence on chromosomes 1 and 4 (P ¼ 0.001) and eight significant linkages on chromosomes 3,7,8,9,11,16,17, and 20 (Po0.05). These findings strongly indicate that some of these regions may harbor susceptibility loci for nicotine dependence. Further analysis of these positive regions by fine mapping and/or association analysis is warranted. To our knowledge, this study presents the most convincing linkage evidence for nicotine dependence in the field.

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“…long-term continuous tobacco use), number of cigarettes smoked daily, and diagnosed nicotine dependence. Heritability estimates for these smoking phenotypes range from 39 -82% for persistent smoking [93,100,101,175], 45 -86% for number of cigarettes smoked daily [65,83,164,178], and 31 -75% for nicotine dependence [80,115,176,179]. In addition, genetic factors also influence nicotine withdrawal symptoms and failed smoking cessation: heritability estimates for nicotine withdrawal symptoms range from 29 -53%, whereas estimates for smoking cessation are 51 -54% [91,127,188,189].…”

Section: Introductionmentioning

confidence: 99%

Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: Converging evidence from human and animal research

Portugal

Gould

2008

Behavioural Brain Research

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Tobacco smoking is a leading preventable cause of death in the United States and produces a major health and economic burden. Although the majority of smokers want to quit, few are successful. These data highlight the need for additional research into the neurobiology of tobacco dependence. Addiction to nicotine, the main psychoactive component of tobacco, is influenced by multiple factors that include individual differences in genetic makeup. Twin studies have demonstrated that genetic factors can influence vulnerability to nicotine addiction, and subsequent research has identified genes that may alter sensitivity to nicotine. In humans, genome-wide and candidate gene association studies have demonstrated that genes encoding nicotinic acetylcholine receptor (nAChR) proteins are associated with multiple smoking phenotypes. Similarly, research in mice has provided evidence that naturally occurring variability in nAChR genes is associated with changes in nicotine sensitivity. Furthermore, the use of genetic knockout mice has allowed researchers to determine the nAChR genes that mediate the effects of nicotine, whereas research with knockin mice has demonstrated that changes to nAChR genes can dramatically alter nicotine sensitivity. This review will examine the genetic factors that alter susceptibility to nicotine addiction, with an emphasis on the genes that encode nAChR proteins.

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Genetic and environmental contributions to smoking

Cited by 97 publications

References 0 publications

Drug Addiction, Dysregulation of Reward, and Allostasis

Drug Addiction, Dysregulation of Reward, and Allostasis

Mapping and verification of susceptibility loci for smoking quantity using permutation linkage analysis

Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: Converging evidence from human and animal research

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