Extension of a Typology of Alcohol Dependence Based on Relative Genetic and Environmental Loading

Johnson, Eric O.; Bree, Marianne Bernadette van den; Gupman, Anne E.; Pickens, Roy W.

doi:10.1111/j.1530-0277.1998.tb03930.x

Cited by 25 publications

(9 citation statements)

References 30 publications

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“…If early onset alcohol use is associated with the more genetically determined form of alcoholism (Pickens et al, 1991; Johnson et al, 1998; Dick et al, 2007; Chen et al, 2011) then it would be expected that genetic factors leading to early drinking and dependence would be manifest. Our results are consistent with this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Genetic and Neurophysiological Correlates of the Age of Onset of Alcohol Use Disorders in Adolescents and Young Adults

et al. 2013

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Discrete time survival analysis (DTSA) was used to assess the age-specific association of event related oscillations (EROs) and CHRM2 gene variants on the onset of regular alcohol use and alcohol dependence. The subjects were 2938 adolescents and young adults ages 12 to 25. Results showed that the CHRM2 gene variants and ERO risk factors had hazards which varied considerably with age. The bulk of the significant age-specific associations occurred in those whose age of onset was under 16. These associations were concentrated in those subjects who at some time took an illicit drug. These results are consistent with studies which associate greater rates of alcohol dependence among those who begin drinking at an early age. The age specificity of the genetic and neurophysiological factors is consistent with recent studies of adolescent brain development, which locate an interval of heightened vulnerability to substance use disorders in the early to mid teens.

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Section: Discussionmentioning

confidence: 99%

Genetic and Neurophysiological Correlates of the Age of Onset of Alcohol Use Disorders in Adolescents and Young Adults

et al. 2013

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“…Most interestingly, common environmental influences played a greater role in use than abuse/dependence, suggesting that the severity of any RDS behavior may have a stronger genetic contribution relative to less severe forms. Moreover, this same group [156] in another study, among Caucasians with alcohol dependence characterized subtypes by differential loading on three dimensions: genetic, general environmental, and dyssocial environmental symptom scales. The mild subtype (60% of men and 66% of women) was distinguished by low mean scores on all three scales; the dyssocial subtype (24% of men and 20% of women) by low mean genetic and general environmental scores but high mean dyssocial environmental scores; and the severe subtype (16% of men and 14% of women) by high scores on the genetic and general environmental scales.…”

Section: Discussionmentioning

confidence: 99%

Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS) Subjects: Selecting Appropriate Phenotypes for Reward Dependence Behaviors

Blum

Chen

Oscar‐Berman

et al. 2011

IJERPH

113

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Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic). Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]). Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants. Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific “reward” phenotype may be a paradigm shift in future association and linkage studies involving dopaminergic polymorphisms and other neurotransmitter gene candidates.

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“…Genetic risk is also clearly conditional upon multiple environmental circumstances, making it difficult to estimate any particular individual's specific risk (Johnson et al 1998). Studies of gene-environment interaction are in theory much easier to perform with suitable animal models, where matings can be arranged and environmental control is relatively easy.…”

Section: Introductionmentioning

confidence: 99%

The Complexity of Alcohol Drinking: Studies in Rodent Genetic Models

2010

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Risk for alcohol dependence in humans has substantial genetic contributions. Successful rodent models generally attempt to address only selected features of the human diagnosis. Most such models target the phenotype of oral administration of alcohol solutions, usually consumption of or preference for an alcohol solution versus water. Data from rats and mice for more than 50 years have shown genetic influences on preference drinking and related phenotypes. This paper summarizes some key findings from that extensive literature. Much has been learned, including the genomic location and possible identity of several genes influencing preference drinking. We report new information from congenic lines confirming QTLs for drinking on mouse chromosomes 2 and 9. There are many strengths of the various phenotypic assays used to study drinking, but there are also some weaknesses. One major weakness, the lack of drinking excessively enough to become intoxicated, has recently been addressed with a new genetic animal model, mouse lines selectively bred for their high and intoxicating blood alcohol levels after a limited period of drinking in the circadian dark. We report here results from a second replicate of that selection and compare them with the first replicate.

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Extension of a Typology of Alcohol Dependence Based on Relative Genetic and Environmental Loading

Cited by 25 publications

References 30 publications

Genetic and Neurophysiological Correlates of the Age of Onset of Alcohol Use Disorders in Adolescents and Young Adults

Genetic and Neurophysiological Correlates of the Age of Onset of Alcohol Use Disorders in Adolescents and Young Adults

Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS) Subjects: Selecting Appropriate Phenotypes for Reward Dependence Behaviors

The Complexity of Alcohol Drinking: Studies in Rodent Genetic Models

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