Genetic and neurophysiological correlates of the age of onset of alcohol use disorders in adolescents and young adults.

Discrete time survival analysis 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 2,938 adolescents and young adults ages 12-25. Results showed that the CHRM2 gene variants and ERO risk factors had hazards which varied considerably with age.

Genome-wide association study of alcohol dependence implicates a region on chromosome 11.

Background: Alcohol dependence is a complex disease, and although linkage and candidate gene studies have identified several genes associated with the risk for alcoholism, these explain only a portion of the risk.

Methods: We carried out a genome-wide association study (GWAS) on a case-control sample drawn from the families in the Collaborative Study on the Genetics of Alcoholism. The cases all met diagnostic criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition; controls all consumed alcohol but were not dependent on alcohol or illicit drugs.

GABRR1 and GABRR2, encoding the GABA-A receptor subunits rho1 and rho2, are associated with alcohol dependence.

The genes encoding several GABA-A receptor subunits, including GABRA2, have been associated with alcoholism, suggesting that variations in gaba signaling contribute to risk. Therefore, as part of a comprehensive evaluation of the GABA receptor genes, we evaluated the potential association of GABRR1 and GABRR2, which encode the rho1 and rho2 subunits of the pentameric GABA-A/GABA-C receptors. GABRR1 and GABRR2 lie in a head to tail orientation spanning 137 kb on chromosome 6q14-16.

Association of NFKB1, which encodes a subunit of the transcription factor NF-kappaB, with alcohol dependence.

A broad region on chromosome 4q has been linked to alcohol dependence (alcoholism). We hypothesized that such broad linkage regions represent the combined action of multiple genes. Seeking to identify genes within that region that are associated with alcoholism, we have tested the association of NFKB1, located at 4q24, with alcoholism.

The relationship between alcohol problems and dependence, conduct problems and diagnosis, and number of sex partners in a sample of young adults.

Background: Heavy drinking is associated with an increased number of sexual partners. This study examined the extent to which alcohol dependence and conduct disorder are associated with the number of sexual partners and membership in a risk group of having a high number of sexual partners (10 or more).

Methods: Data were obtained by personal interview from 601 relatives (aged 18 to 25 years) of alcohol-dependent probands who participated in the Collaborative Study on the Genetics of Alcoholism (COGA) project.

Family-based association analyses of alcohol dependence phenotypes across DRD2 and neighboring gene ANKK1.

Background: There is an extensive and inconsistent literature on the association of the dopamine D2 receptor gene (DRD2) with alcohol dependence. Conflicting results have been attributed to differences in the severity of the alcohol dependence phenotype across studies, failure to exclude related disorders from comparison groups, and artifacts of population-stratification. Recently the genetic polymorphism most widely analyzed in DRD2, Taq1A, has been discovered to reside in a neighboring gene, ankyrin repeat and kinase domain containing 1 (ANKK1), located 10 kb downstream from DRD2.

Association analyses of the serotonin transporter gene with lifetime depression and alcohol dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample.

The objective of this study was to analyze association of the serotonin transporter gene 5-HTTLPR polymorphism on lifetime depression and alcohol dependence in the Collaborative Study on the Genetics of Alcoholism sample. We conducted family-based association analyses in 1913 Caucasians genotyped for the 5-HTTLPR polymorphism. We found evidence for association of the short allele with depression, but no evidence of association with alcohol dependence.

Association of CHRM2 with IQ: converging evidence for a gene influencing intelligence.

The cholinergic neurotransmitter system is thought to be involved in many aspects of memory, attention, and higher cognition. In the Collaborative Study on the Genetics of Alcoholism (COGA) sample, we have previously reported linkage and association to the cholinergic muscarinic 2 receptor gene (CHRM2) on chromosome 7 with evoked EEG oscillations (Jones et al. 2004), providing evidence that this gene may be involved in human brain dynamics and cognition.

Linkage analyses of IQ in the collaborative study on the genetics of alcoholism (COGA) sample.

Intelligence, as measured by standardized psychological tests, has been shown to be highly heritable, though identifying specific genes influencing general intelligence has proven difficult. We conducted genome-wide linkage analyses to identify chromosomal regions containing genes influencing intelligence, as measured by WAIS full-scale IQ (FSIQ), performance IQ (PIQ) and verbal IQ (VIQ). Non-parametric multipoint linkage analyses were conducted with Merlin-regress software, using a sample of 1,111 genotyped and phenotyped individuals from 201 families, ascertained as part of the Collaborative Study on the Genetics of Alcoholism (COGA).

Evaluation of a level of response to alcohol-based structural equation model in adolescents.

Objective: A low level of response (LR) to alcohol relates to a family history of alcoholism and predicts future heavier drinking and alcohol-related problems. The current analyses evaluate how LR functions within the context of a Social Information Processing Model, using 238 subjects aged 13 to 19 years from the Collaborative Study on the Genetics of Alcoholism (COGA).

Method: A structural equation model (SEM) was used to evaluate the relationship among (1) a family history (FH) of alcoholism, (2) the LR to alcohol, (3) expectations as measured by the Alcohol Expectancy Questionnaire and (4) the recent pattern of drinking among parents in the home as predictors of the maximum recent quantity of drinking, the maximum number of drinks ever consumed in 24 hours and the number of alcohol problems in the teenage subjects.

Association of GABRG3 with alcohol dependence.

Background: Evidence from human, animal, and in vitro cell models suggests that gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the human central nervous system, is involved in many of the neurochemical pathways that affect alcohol use, abuse, and dependence. Both linkage and association to the region on chromosome 15q that contains a cluster of GABAA receptor genes have previously been reported, but the role of these genes in alcoholism remains inconclusive.

Methods: We conducted family-based association analyses by using a large sample of multiplex alcoholic families collected as part of the Collaborative Study on the Genetics of Alcoholism, to test for an association between alcohol dependence and the GABAA receptor genes clustered on chromosome 15q.

Theta power in the EEG of alcoholics.

Background: In this study, the magnitude and spatial distribution of theta power in the resting EEG were examined to explore the changes in the neurophysiological status of the alcoholic brain. Some state- and trait-related issues of theta power increases in the EEG of alcoholics were also examined.

Methods: Absolute theta (3-7 Hz) power in eyes-closed EEGs of 307 alcohol-dependent subjects and 307 age- and gender-matched unaffected controls were compared by using a repeated-measures ANOVA for the entire region and three subregions (frontal, central, and parietal) separately.