Alcohol Acceptance, Preference, and Sensitivity in Mice. II. Quantitative Trait Loci Mapping Analysis Using BXD Recombinant Inbred Strains

Quantitative trait loci (QTL) mapping of complex phenotypes has emerged as an important feature of the recombinant inbred (Rl) strain methodology. In this second study of our series on alcohol-related behaviors in mice, we examine alcohol acceptance, preference, and hypnotic dose sensitivity (HDS) to a standard dose of alcohol measured in BXD RI strains to identify candidate QTL regions responsible for their heritability. We detected highly significant marker associations for acceptance on chromosome 12 (Eif4e) , for preference on chromosome 1 (D1Rti2) and chromosome 7 (D7Mit7) , and for HDS on chromosome 7 (Mpmv1). These are the strongest QTL associations that we detected, but several other candidate QTL regions are reported. Given the limited number of BXD RI strains available, the large number of markers used herein, and the consequent chance of identifying false marker associations, these RI QTL mapping results must be seen as tentative, but an important first step toward identifying QTL for alcohol-related behaviors.     

Correlations of Alcohol Consumption with Related Covariates and Heritability Estimates in Older Adult Males Over a 14- to 18-Year Period: The NHLBI Twin Study

Consistent maximum-likelihood heritability estimates of consumption of alcoholic beverages were observed at three separate times during a 14- to 18-year period in adult twin males initially aged 42-–56 years in 1969–1973. Log transformation of the average number of drinks/ week of the returnees to all three examinations was examined relative to potential covariates representing both antecedents of drinking alcohol and consequences of alcohol consumption. Significant relationships were noted for 38 of the covariates at one or more of the separate examinations, including positive correlations with smoking, coffee consumption, high-density lipoprotein cholesterol, mean corpuscular volume, systolic blood pressure, uric acid and behavioral measures, and negative correlations with blood urea nitrogen, red blood cell count, tea consumption, and tricep skinfolds. Analysis of the average alcohol consumption adjusted for nine independent covariater selected from multiple stepwise regression resulted in a modest decline in maximum-likelihood heritability estimates compared with unadjusted data, but little difference from heritability estimates obtained when abstainers from alcohol (no alcoholic beverages consumed at all three examinations) were excluded. The most striking effect of omitting abstainers from alcohol was the decline in the intraclass correlations in dizygotic twins. Bivariate analyses of alcohol and individual covariates revealed the phenotypic correlation between alcohol consumption and a measure of hostility was primarily environmental, that for high-density lipoprotein, smoking and coffee drinking with alcohol was primarily genetic, and the phenotypic correlation between alcohol consumption and mean corpuscular volume had both significant genetic and environmental correlations. Comparison with other twin studies in males suggested relatively consistent estimates of genetic variance, despite wide variation in subject characteristics, study design and methods, and measure of alcohol consumption.     

The University of California, San Francisco Family Alcoholism Study. I. Design, methods, and demographics

BACKGROUND: The University of California, San Francisco (UCSF) Family Alcoholism Study is a project designed to identify genetic loci that influence susceptibility to alcohol dependence and related phenotypes. Evidence supports a substantial genetic contribution to alcoholism susceptibility. However, the genetic epidemiology of alcoholism is complex, and its clinical manifestation is heterogeneous, making phenotype definition and demonstration of linkage difficult. Despite these challenges, some progress has been made toward identifying genes. METHODS: The UCSF Family Alcoholism Study used a small family design, focusing primarily on sibling pairs and parent-child trios for linkage and association studies. Alcoholism-related phenotypes were assessed through interview and self-report questionnaires, with a focus on unidimensional and subphenotypical traits. Data-driven approaches to determining the most promising phenotypes for genetic analysis are being used. Both genome-wide scan and candidate gene approaches were used. RESULTS: The study enrolled 2154 individuals from 970 families from December 1995 through January 2003. Test-retest and interrater reliability for clinical data are very good, and power estimates suggest that this study will have adequate power by linkage analysis to detect loci with moderate effects. Design, methods, and sample demographics of the UCSF Family Study are presented, along with intrafamilial correlations for primary diagnostic phenotypes. CONCLUSIONS: Plans for genetic analysis, novel approaches to phenotype refinement, and the implications of ascertainment bias for heritability estimates are discussed.     

Common Genetic Contributions to Alcohol and Cannabis Use and Dependence Symptomatology

Background: Despite mounting evidence that use of and dependence on alcohol and cannabis are influenced by heritable factors, the extent to which heritable influences on these phenotypes overlap across the 2 substances has only rarely been explored. In the current study, we quantified cross‐substance overlap in sources of variance and estimated the degree to which within‐substance associations between use and dependence measures are attributable to common genetic and environmental factors for alcohol and cannabis. Methods: The sample was comprised of 6,257 individuals (2,761 complete twin pairs and 735 singletons) from the Australian Twin Registry, aged 24 to 36 years. Alcohol and cannabis use histories were collected via telephone diagnostic interviews and used to derive an alcohol consumption factor, a frequency measure for cannabis use, and DSM‐IV alcohol and cannabis dependence symptom counts. Standard genetic analyses were conducted to produce a quadrivariate model that provided estimates of overlap in genetic and environmental influences across the 4 phenotypes. Results: Over 60% of variance in alcohol consumption, cannabis use, and cannabis dependence symptoms, and just under 50% of variance in alcohol dependence (AD) symptoms were attributable to genetic sources. Shared environmental factors did not contribute significantly to the 4 phenotypes. Nearly complete overlap in heritable influences was observed for within‐substance measures of use and dependence symptoms. Genetic correlations across substances were 0.68 and 0.62 for use and dependence symptoms, respectively. Conclusions: Common heritable influences were evident for alcohol and cannabis use and for AD and cannabis dependence symptomatology, but findings indicate that substance‐specific influences account for the majority of the genetic variance in the cannabis use and dependence phenotypes. By contrast, the substantial correlations between alcohol use and AD symptoms and between cannabis use and cannabis dependence symptoms suggest that measures of heaviness of use capture much of the same genetic liability to alcohol‐ and cannabis‐related problems as dependence symptomatology.     

Subjective intoxication in response to alcohol challenge: heritability and covariation with personality,breath alcohol level,and drinking history

BACKGROUND: Numerous studies have identified differences in subjective response to alcohol in subjects differentiated by family history of alcoholism. Results suggest that genetic influences on individual variation in subjective response to alcohol may be a mechanism for genetic effects on alcohol problems. However, direct evidence for genetic effects on subjective response to alcohol is very limited. METHODS: In a sample of 99 adult twin pairs, we studied genetic influences on subjective intoxication after alcohol challenge. The twins ingested a standard dose of ethanol (0.70 g/kg for men/0.65 g/kg for women), and two measures of subjective response to alcohol were assessed. RESULTS: Genetic effects on variation in subjective intoxication reported 1 hr after drinking were significant and substantial: heritability was 0.60 for a 22-item scale and 0.48 for a brief 2-item measure. Self-report measures of neuroticism, psychasthenia, hostility, and family problems shared significant genetic covariation with subjective intoxication. Achieved breath alcohol level, rate of change in breath alcohol on the descending limb, and individual drinking history all shared familial variation with subjective intoxication. No significant genetic effects for subjective intoxication were found 2 hr after drinking, but familial influences remained present, and many of the same personality, drinking history, and breath alcohol variables were predictive of intoxication. CONCLUSIONS: Subjective response to alcohol is heritable, and genetic effects on subjective intoxication are partly shared with genetic effects on personality.     

A cross-generational comparison of alcohol challenges at about age 20 in 40 father-offspring pairs

BACKGROUND: A low level of response (LR) to alcohol is one of several genetically-influenced phenotypes associated with an elevated risk for heavy drinking and alcoholism. While most studies support the influence of genes for this characteristic, no data to date have addressed how LR established from alcohol challenges performs in similarly aged subjects across generations. METHODS: Between 1978 and 1988, 18-to-25-year-old non-alcohol-dependent Caucasian male drinkers participated in the San Diego Prospective Study alcohol challenges. The paradigms included self-reports of feelings of "High" and "Intoxication," as well as alcohol-related changes in body sway. In recent years, 40 18-to-29-year-old offspring of 25 of these original probands were tested using a similar protocol. RESULTS: Despite the passage of two decades between laboratory sessions across generations, for family history positive (FHP) subjects, significant positive correlations were observed for subjective feelings of intoxication and body sway after alcohol. Parent-offspring correlations were in the predicted direction for subjective feelings for family history negatives (FHNs), but were not significant. Across offspring, LR values were lower for FHPs overall, with significant differences at 60 or 90 min for five items. CONCLUSIONS: The similarities in LR across generations, while not proving heritability, are consistent with prior reports regarding genetic influences in the LR to alcohol. The significant correlations across generations and over two decades support the reliability of the alcohol challenge results.     

Measures of current alcohol consumption and problems: two independent twin studies suggest a complex genetic architecture

Background: Twin studies demonstrate that measures of alcohol consumption (AC) show evidence of genetic influence, suggesting they may be useful in gene identification efforts. The extent to which these phenotypes will be informative in identifying susceptibility genes involved in alcohol dependence depends on the extent to which genetic influences are shared across measures of AC and alcohol problems. Previous studies have demonstrated that AC reported for the period of heaviest lifetime drinking shows a large degree of genetic overlap with alcohol dependence; however, many studies with genetic material assess current AC. Further, there are many different aspects of AC that can be assessed (e.g., frequency of use, quantity of use, and frequency of intoxication). Methods: Here, we use data from 2 large, independent, population‐based twin samples, FinnTwin 16 and The Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, to examine the extent to which genetic influences are shared across many different measures of AC and alcohol problems. Results: Genetic correlations across current AC measures and alcohol problems were high across both samples. However, both samples suggest a complex genetic architecture with many different genetic factors influencing various aspects of current AC and problems. Conclusions: These results suggest that careful attention must be paid to the phenotype in efforts to “replicate” genetic effects across samples or combine samples for meta‐analyses of genetic effects influencing susceptibility to alcohol‐related outcomes.     

Genetic and environmental influences on the rate of progression to alcohol dependence in young women

Background: The development of alcohol dependence (AD) involves transitions through multiple stages of drinking behaviors and is shaped by both heritable and environmental influences. We attempted to capture this dynamic process by characterizing genetic and environmental contributions to the rate at which women progressed through 3 significant transitions along the pathway to AD: nonuse to initiation, initiation to onset of first alcohol‐related problem, and first problem to onset of AD. Methods: The sample consisted of 3,546 female twins from the Missouri Adolescent Female Twin Study. Participants ranged in age from 18 to 29 years. Retrospective reports of alcohol use histories were collected by telephone diagnostic interview and transition times between drinking milestones were coded ordinally. Standard genetic analyses were conducted in Mx to derive a trivariate model that provided estimates of genetic and environmental influences that were common as well as specific to the 3 transition times. Results: Heritable influences were found for rate of progression across all 3 transitions, accounting for 30 to 47% of the variance in transition times. Shared environmental contributions were evident only in rate of progression from nonuse to initiation (i.e., age at first drink). Heritable contributions to the rate of movement through successive drinking milestones were attributable to a common factor, whereas environmental influences were transition‐specific. Conclusions: The current study is unique in its use of a genetically informative design to document the rate of movement between drinking milestones in a female sample and to examine genetic contributions to multiple transition times over the course of AD development. Results indicate that an earlier report of heritability for males in rate of progression from regular drinking to AD generalizes to women and to other alcohol stage transitions. Findings also suggest the need to consider stage‐specific environmental contributions to alcohol outcomes in developing interventions.     

US state alcohol sales compared to survey data, 1993–2006

Aims Assess long‐term trends of the correlation between alcohol sales data and survey data. Design Analyses of state alcohol consumption data from the US Alcohol Epidemiologic Data System based on sales, tax receipts or alcohol shipments. Cross‐sectional, state annual estimates of alcohol‐related measures for adults from the US Behavioral Risk Factor Surveillance System using telephone surveys. Setting United States. Participants State alcohol tax authorities, alcohol vendors, alcohol industry (sales data) and randomly selected adults aged ≥ 18 years 1993–2006 (survey data). Measurements State‐level per capita annual alcohol consumption estimates from sales data. Self‐reported alcohol consumption, current drinking, heavy drinking, binge drinking and alcohol‐impaired driving from surveys. Correlation coefficients were calculated using linear regression models. Findings State survey estimates of consumption accounted for a median of 22% to 32% of state sales data across years. Nevertheless, state consumption estimates from both sources were strongly correlated with annual r‐values ranging from 0.55–0.71. State sales data had moderate‐to‐strong correlations with survey estimates of current drinking, heavy drinking and binge drinking (range of r‐values across years: 0.57–0.65; 0.33–0.70 and 0.45–0.61, respectively), but a weaker correlation with alcohol‐impaired driving (range of r‐values: 0.24–0.56). There were no trends in the magnitude of correlation coefficients. Conclusions Although state surveys substantially underestimated alcohol consumption, the consistency of the strength of the association between sales consumption and survey data for most alcohol measures suggest both data sources continue to provide valuable information. These findings support and extend the distribution of consumption model and single distribution theory, suggesting that both sales and survey data are useful for monitoring population changes in alcohol use.     

Indicators of Genetic and Environmental Influence in Alcohol-Dependent Individuals

Although much is known about genetic and environmental influences in alcohol dependence at the population level, little is known about the relative contribution of such influences on individuals. As an initial step toward individual assessment, concordance for the Diagnostic Interview Schedule, version III alcohol symptoms was determined in a sample ( n = 113) of male monozygotic (MZ) and dizygotic (DZ) twins. Items were assigned to a genetic or environmental scale on the basis of significant MZ/DZ differences in proband-wise concordance rates. Weights were assigned to items based on factor analyses. For the genetic scale, significant differences were found between MZ and DZ intraclass correlations. No significant differences were found between MZ and OZ correlations on the environmental scale. When scores on the environmental scale were controlled, genetic scale scores were correlated with earlier age of onset of alcohol problems and a shorter interval between first intoxication and onset of alcohol problems. When scores on the genetic scale were controlled, environmental scale scores were correlated with later age of onset of alcohol problems and a longer interval between first intoxication and onset of alcohol problems. These results suggest it is possible to assess relative influence of genetic and environmental factors in individual cases of alcohol dependence.     

Genetic and environmental influences on social support in later life: a longitudinal analysis.

The present study assessed the etiology of individual differences in social support over a six-year period. The availability of friend support, family support, and the perceived adequacy of the social support network was assessed three times using identical and same-gender fraternal twins reared together and reared apart from the Swedish Adoption/Twin Study of Aging. Results are based on the pairwise responses at the three occasions of measurement (labeled Q1, Q2, and Q3): 462 pairs at Q1 (assessed October 1984), 474 pairs at Q2 (October 1987), and 431 pairs at Q3 (October 1990). The longitudinal phenotypic correlations (ranging from .49 to .77) indicate that social support is a moderately stable characteristic. Qualitative genetic model-fitting analyses resulted in significant heritability estimates for the social support measures at all three measurement occasions. Results also indicate considerable stability in genetic effects across measurement occasions, with genetic correlations ranging from .65 to .97. Nonshared environmental influences were substantial contributors to social support, but were less stable across the measurement occasions, with correlations ranging from .07 to .52.     

Analysis of heritability of hormonal responses to alcohol in twins: beta-endorphin as a potential biomarker of genetic risk for alcoholism

BACKGROUND: Hormonal responses to alcohol have been reported to differ in subjects with and without a family history of alcoholism which suggests that alcohol-induced hormonal changes might be used to identify individuals who are at elevated genetic risk for developing alcoholism. However, before a biological response can be used as a marker of genetic risk for disease, it must first be demonstrated that the response is, in fact, heritable. The present study was designed to determine whether hormonal responses to alcohol are heritable. METHODS: The adrenocorticotropic hormone (ACTH), beta-endorphin (beta-E), cortisol (CORT), and prolactin (PRL) responses to alcohol were examined in male and female identical (monozygotic or MZ) and fraternal (dizygotic or DZ) twin pairs. Male subjects consumed 0.35 g ethanol/kg body weight (BW) and females consumed 0.325 g ethanol/kg BW in each of two alcohol drinking sessions administered 1 hr apart (total dose of 0.7 g/kg BW in males and 0.65 g/kg BW in females). Plasma hormone content was analyzed in samples collected before (resting conditions) and at 15, 60, 75, 120, 180, and 240 min after onset of drinking. Hormonal responses to alcohol were examined with twin analyses using the TWINAN90 program. A separate analysis was performed for each of the four hormones. A subset of subjects from each zygosity was seen on two separate occasions to establish retest reliability. Heritability of hormonal responses to alcohol was estimated using the intraclass correlation approach before and after removing the contribution of covariates that have the potential of influencing the plasma levels of these hormones. RESULTS: Resting plasma levels of all four hormones were within the expected range, and the beta-E, ACTH, and PRL responses to the alcohol challenge evidenced good test-retest reliability. Of the four hormones examined, the only one that showed significant heritability after alcohol drinking was beta-E. Heritability estimates were not altered for any of the four hormones after removal of the variance contributed by covariates, such as gender and age. CONCLUSIONS: Taken together with other recent findings, the results suggest that the beta-E response to alcohol may represent a new biomarker that can be used to identify individuals who are at elevated genetic risk for developing alcoholism.     

Alcohol Effects on the Heritability of EEG Spectral Power

To estimate the effects of a moderate dose of alcohol on heritability of the EEG power spectrum, 53 monozygotic and 38 like-sexed dizygotic Caucasian twin pairs (aged 30.0 ± 7.0 years) were studied. Subjects were asked not to drink alcohol for 2 days and to fast after midnight before a protocol of: (1) a low fat meal at 8:00 AM; (2) a baseline EEG recording; (3) ingestion of alcohol over 10 min, which raised the breath alcohol concentration to 0.057 ± 0.017% (SD); followed by (4) a postalcohol EEG recording 35.1 ± 5.7 (SD) min after the start of drinking. One previous study (Propping, P., Hum. Genet. 35: 309–334,1977) found that heritability (H²), the fraction of total variance in the EEG power that is attributable to genetic influences, increased after alcohol administration. In the current study, H² of log-transformed, body-weight-adjusted spectral band power increased after alcohol for the θ-, α-slow, α-fast, β-slow, and β-fast bands (from an average of 0.47 to an average of 0.80). The increase in heritability was accompanied by a significant decrease in the within-pair differences of monozygotic cotwins for all of the same frequency bands except β-fast. Because within-pair differences are expected to contain only environmental factors for the genetically identical individuals, it was concluded that alcohol decreases environmental variation of EEG power spectral density, causing the increase in H².     

Neurochemical characteristics associated with ethanol preference in selected alcohol-preferring and -nonpreferring rats: a quantitative microdialysis study

BACKGROUND: Rodent lines selected for alcohol preference and nonpreference have been used extensively to determine the neurobiological basis of alcohol-seeking behavior. Evidence suggests that innate differences in the mesolimbic dopamine and serotonin systems may contribute to disparate alcohol-seeking behaviors between these selected lines. Therefore, the purpose of this study was to identify neurochemical characteristics which may predict ethanol preference in selected alcohol-preferring and -nonpreferring rats [high-alcohol-preferring (HAD), low-alcohol-preferring (LAD), Alko alcohol (AA), Alko nonalcohol (ANA), Wistar]. METHODS: Basal release of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of ethanol-naive rats was analyzed for its relationship with subsequent measures of ethanol preference. Initially, basal extracellular DA and 5-HT levels were measured by "no-net-flux" quantitative microdialysis. Subsequently, the dopaminergic response to systemic ethanol administration (1.5 g/kg; intraperitoneal) was determined. After completion of the neurochemical tests, the rats received unlimited two-bottle, free-choice access to 10% (w/v) ethanol and water in the home cage for 28 days. RESULTS: Analysis of the data across individual animals revealed that extracellular dopamine levels ([DA]e; r = + 0.64;p < 0.006) and the percent of baseline increase in DA (%incrDA; r = + 0.77;p < 0.001) due to ethanol were significant predictors of ethanol preference. Comparison of the data between genetic lines yielded a significant relationship between preference and %incrDA (r = + 0.87; p < 0.05). Analysis of the data across animals within each line and their respective control line determined that in the AA/ANA line pair (r = + 0.67; p < 0.03) and Wistar line (r = + 0.66; p < 0.03) %incrDA was a significant predictor of preference. In the HAD/LAD line pair, %incrDA (r = + 0.56; p < 0.005) and [DA]e (r = + 0.86; p < 0.004) were significant predictors of ethanol preference. CONCLUSIONS: Overall, these findings suggest that elevated extracellular levels of dopamine within the nucleus accumbens and a greater responsivity to enhancements in DA release by ethanol may be factors which contribute to high-alcohol preference. Furthermore, the data suggest that alcohol may be more reinforcing in animals that exhibit an enhanced dopaminergic response to the first ethanol exposure, and that this effect may subsequently be associated with high-alcohol-seeking behavior.     

Sex Differences in the Sources of Genetic Liability to Alcohol Abuse and Dependence in a Population-Based Sample of U.S. Twins

BACKGROUND: There are substantial sex differences in all levels of alcohol involvement among U.S. adults. The goal of this study was to test whether the magnitude and sources of genetic and environmental influences on liability for alcohol abuse and dependence differ for men and women. METHODS: Structured personal interviews were used to assess DSM-III-R- and DSM-IV-defined alcohol abuse and dependence among 5091 male and 4168 female twins (including 1546 identical, 1128 same-sex fraternal, and 1423 opposite-sex pairs) born in Virginia between 1934 and 1974. Twin correlations were analyzed using structural equation modeling. RESULTS: The magnitude of twin-pair resemblance was similar across several definitions of alcoholism and was substantially higher among identical than fraternal pairs. The proportion of population variation in liability attributed to genetic factors was substantial among both women (55-66%) and men (51-56%), and we found little evidence of a role of environmental factors shared by family members. In all definitions studied, we could reject a model that the genetic sources of liability in the two sexes overlap completely. CONCLUSION: In this first population-based study of alcoholism among male and female twins from the U.S., we found that genetic factors play a major role in the development of alcoholism in both sexes, that the magnitudes of genetic influence were equally high for men and women, and that the genetic sources of vulnerability are partially, but not completely, overlapping in men and women.     

Alcohol Reactions in Subjects of European Descent: Effects on Alcohol Use and on Physical and Psychomotor Responses to Alcohol

Self-reports of reactions to small amounts of alcohol, obtained between 1990 and 1992, were compared with reports of alcohol use, obtained in 1990–1992 and also in 1979–1981, in twin subjects of European descent. Data on subjective, physiological, psychomotor, and metabolic responses to a test dose of alcohol, taken in 1979–1981, were also available. Alcohol reactions were more common in women than in men, and were associated with less alcohol use, both at the time that information about reactions was obtained and as recorded on average 12 years previously, in both sexes. Physiological and psychomotor responses to alcohol were similar across the reaction groups, except that deterioration in standing steadiness was greater in those who subsequently reported adverse reactions to alcohol. Contrary to expectation, skin temperature changes after alcohol were less in the subjects who reported always reacting to alcohol than in the other groups. Subjective reports of intoxication were greatest in subjects who subsequently reported alcohol reactions. The pattern of twin pair concordance for reactions suggests low heritability, so alcohol reactions in subjects of European descent are not caused by a single gene of high penetrance of the type found in the Asian alcohol flush reaction.     

Alcohol Preference and Hepatic Alcohol Dehydrogenase Activity in Adult Long-Evans Rats is Affected by Intrauterine Sibling Contiguity

Alcohol preference and hepatic alcohol dehydrogenase activity in adult rats are known to be sexually dimorphic. Intrauterine sibling contiguity (the intrauterine position of a fetus relative to adjacent siblings of the same or opposite sex) alters selected reproductive, behavioral and enzymatic sexual dimorphisms via intersibling sex hormone transfer. We postulated that sibling contiguity would affect alcohol preference and hepatic alcohol metabolism in adult rats. The results of our study demonstrate that adult mMm male Long-Evans rats (genetic male rat developing in utero between two male siblings) had significantly lower ethanol preference, attained higher blood alcohol levels after standard ethanol "challenge" doses and had significantly lower hepatic alcohol dehydrogenase activity than either male siblings developing in utero between two females (fMf) or genetic females developing between two males or between two females (mFm or fFf). Hepatic cytosolic aldehyde dehydrogenase activity was higher in adult female than male rats regardless of nearest neighbor siblings. It is suggested that the differences in ethanol preference and hepatic alcohol dehydrogenase activity between the adult mMm and fMf male rats is due to differences in prenatal hormonal environment which can modulate sexual dimorphisms in alcohol intake and metabolism in the adult.     

The genetics of alcohol intake and of alcohol dependence

BACKGROUND: Because alcohol has multiple dose-dependent consequences, it is important to understand the causes of individual variation in the amount of alcohol used. The aims of this study were to assess the long-term repeatability and genetic or environmental causes of variation in alcohol intake and to estimate the degree of overlap with causes of susceptibility to alcohol dependence. METHODS: Data were used from three studies conducted between 1980 and 1995 on volunteer adult male and female Australian twin subjects. In each study, alcohol intake was reported both as quantity x frequency and as past-week data. Repeatability was calculated as correlations between occasions and between measures, and the effects of genes and environment were estimated by multivariate model fitting to the twin pair repeated measures of alcohol use. Relationships between mean alcohol use and the lifetime history of DSM-III-R alcohol dependence were tested by bivariate model fitting. RESULTS: Repeatability of the alcohol intake measures was between 0.54 and 0.85, with the highest repeatability between measures within study and the lowest repeatability between the first and last studies. Reported alcohol consumption was mainly affected by genetic factors affecting all times of study and by nonshared environmental factors (including measurement error) unique to each time of study. Genes that affect alcohol intake do affect alcohol dependence, but genetic effects unique to dependence are also significant; environmental effects are largely unique to either intake and dependence. CONCLUSIONS: Nearly all the repeatable component of variation in alcohol intake is due to genetic effects. Genes affecting intake also affect dependence risk, but there are other genes that affect dependence alone. Studies aiming to identify genes that affect alcohol use disorders need to test loci and candidate genes against both phenotypes.     

Estimates of the mean alcohol concentration of the spirits, wine, and beer sold in the United States and per capita consumption: 1950 to 2002

BACKGROUND: Estimates of per capita consumption of alcohol in the United States require estimates of the mean alcohol content by volume (%ABV) of the beer, wine, and spirits sold to convert beverage volume to gallons of pure alcohol. METHODS: The mean %ABV of spirits is estimated for each year from 1950 to 2002 and for each state using the %ABV of major brands and sales of sprits types. The mean %ABV of beer and wine is extrapolated to cover this period based on previous estimates. These mean %ABVs are then applied to alcohol sales figures to calculate new yearly estimates of per capita consumption of beer, wine, spirits, and total alcohol for the United States population aged 15 and older. RESULTS: The mean %ABV for spirits is found to be lower than previous estimates and to vary considerably over time and across states. Resultant per capita consumption estimates indicate that more alcohol was consumed from beer and less from wine and spirits than found in previous estimates. CONCLUSIONS: Empirically based calculation of mean %ABV for beer, wine, and spirits sold in the United States results in different and presumably more accurate per capita consumption estimates than heretofore available. Utilization of the new estimates in aggregate time-series and cross-sectional models of alcohol consumption and related outcomes may improve the accuracy and precision of such models.     

Timing of first alcohol use and alcohol dependence: evidence of common genetic influences

Aims   To estimate the magnitude of genetic and environmental influences on timing of first alcohol use and alcohol dependence (AD) and to quantify the overlap in these influences across the two alcohol-related outcomes.
Participants    The sample consisted of 5382 twins (2691 complete pairs), aged 24–36 years, from the Australian Twin Registry.
Measurements   History of alcohol use and DSM-IV alcohol dependence were assessed by structured telephone interview.
Findings   In both sexes, the relationship between age at first alcohol use and risk for AD followed a linear trend, such that the highest rates of AD were observed in individuals who began drinking at an earlier than average age (14 years or younger). Heritability estimates for timing of first alcohol use and AD were 36% and 53%, respectively. Shared environmental factors accounted for 15% of variance in initiation. There was no evidence of shared environmental influences on AD. The genetic correlation between timing of first alcohol use and AD was 0.59.
Conclusions   Findings highlight the substantial role of genetics in the development of AD and the early manifestation of that genetic risk in the timing of alcohol use initiation which, unlike AD, is also influenced to a modest degree by shared environmental factors. The considerable overlap in heritable influences—and the virtual absence of overlap in individual-specific environmental influences—on initiation of alcohol use and AD indicates that the association between age at first drink and AD is attributable in large part to common genetic sources of variance.