Dataset Information

The role of GABRA2 in alcohol dependence, smoking, and illicit drug use in an Australian population sample.

ABSTRACT: Multiple studies have shown that genetic variation in the alpha-2 subunit of the gamma-aminobutyric acid type A (GABA(A)) receptor (GABRA2) is associated with risk for alcohol dependence. Recent reports have suggested that GABRA2 may exert its influence on dependence through factors such as sensitivity to alcohol's intoxicating effects and that GABRA2 may also contribute to a common underlying genetic vulnerability to both alcohol and drug dependence. The present study tested for association between GABRA2 and alcohol dependence, smoking, and illicit drug use within the Australian population.We genotyped 11 single nucleotide polymorphisms (SNPs) within or flanking GABRA2 in 4597 subjects (34.6% males) from 2618 families comprising 814 monozygotic pairs, 1177 dizygotic pairs, and 627 twins whose co-twin did not participate. Family-based association tests were conducted for binary and quantitative measures of alcohol dependence, smoking, and cannabis and other illicit drug use.We observed evidence of association (p < 0.05) between multiple GABRA2 SNPs and quantitative measures of alcohol dependence, including symptom scores and principal component factor scores from the 9 criteria for DSM-IV alcohol dependence, in the opposite direction to that previously reported. In contrast, GABRA2 was not associated overall with dichotomous measure of alcohol dependence nor with smoking, cannabis, or illicit drug use.The GABRA2 allelic associations found in clinical case-control studies have detectable but minor effects on DSM-defined alcohol dependence in the general community. Systematic comparisons of allelic effects on alcohol dependence in clinical cases and in the general community are required.

SUBMITTER: Lind PA

PROVIDER: S-EPMC2575093 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The role of GABRA2 in alcohol dependence, smoking, and illicit drug use in an Australian population sample.

Lind Penelope A PA Macgregor Stuart S Agrawal Arpana A Montgomery Grant W GW Heath Andrew C AC Martin Nicholas G NG Whitfield John B JB

Alcoholism, clinical and experimental research 20080822 10

<h4>Background</h4>Multiple studies have shown that genetic variation in the alpha-2 subunit of the gamma-aminobutyric acid type A (GABA(A)) receptor (GABRA2) is associated with risk for alcohol dependence. Recent reports have suggested that GABRA2 may exert its influence on dependence through factors such as sensitivity to alcohol's intoxicating effects and that GABRA2 may also contribute to a common underlying genetic vulnerability to both alcohol and drug dependence. The present study tested ...[more]

PMID: 18727688

Similar Datasets

Project description:Study objectivesBasic experiments support the impact of hypocretin on hyperarousal and motivated state required for increasing drug craving. Our aim was to assess the frequencies of smoking, alcohol and drug use, abuse and dependence in narcolepsy type 1 (NT1, hypocretin-deficient), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH) (non-hypocretin-deficient conditions), in comparison to controls. We hypothesized that NT1 patients would be less vulnerable to drug abuse and addiction compared to other hypersomniac patients and controls from general population.MethodsWe performed a cross-sectional study in French reference centres for rare hypersomnia diseases and included 450 adult patients (median age 35 years; 41.3% men) with NT1 (n = 243), NT2 (n = 116), IH (n = 91), and 710 adult controls. All participants were evaluated for alcohol consumption, smoking habits, and substance (alcohol and illicit drug) abuse and dependence diagnosis during the past year using the Mini International Neuropsychiatric Interview.ResultsAn increased proportion of both tobacco and heavy tobacco smokers was found in NT1 compared to controls and other hypersomniacs, despite adjustments for potential confounders. We reported an increased regular and frequent alcohol drinking habit in NT1 versus controls but not compared to other hypersomniacs in adjusted models. In contrast, heavy drinkers were significantly reduced in NT1 versus controls but not compared to other hypersomniacs. The proportion of patients with excessive drug use (codeine, cocaine, and cannabis), substance dependence, or abuse was low in all subgroups, without significant differences between either hypersomnia disorder categories or compared with controls.ConclusionsWe first described a low frequency of illicit drug use, dependence, or abuse in patients with central hypersomnia, whether Hcrt-deficient or not, and whether drug-free or medicated, in the same range as in controls. Conversely, heavy drinkers were rare in NT1 compared to controls but not to other hypersomniacs, without any change in alcohol dependence or abuse frequency. Although disruption of hypocretin signaling in rodents reduces drug-seeking behaviors, our results do not support that hypocretin deficiency constitutes a protective factor against the development of drug addiction in humans.

Project description:Background and objectivesPrevious studies suggest that tobacco, alcohol, and illicit drug use is associated with CKD. We examined the associations of substance use with CKD progression and all-cause mortality among patients with CKD.Design, setting, participants, & measurementsThe Chronic Renal Insufficiency Cohort Study is a prospective, longitudinal cohort study among 3939 participants with CKD in the United States. Self-reported tobacco smoking, alcohol drinking, marijuana use, and hard illicit drug (cocaine, heroin, or methamphetamine) use were obtained at baseline and annual follow-up visits. CKD progression was defined as incident ESKD or halving of eGFR. Substance use was modeled as the cumulative average exposure to capture both recent and long-term use in multivariable time-dependent Cox regression.ResultsOver a median 5.5-year follow-up, 1287 participants developed CKD progression, and 1001 died. Baseline proportions of tobacco smoking, alcohol drinking, marijuana use, and hard illicit drug use were 13%, 20%, 33%, and 12%, respectively. Compared with nonsmoking throughout follow-up, multivariable-adjusted hazard ratios for persistent tobacco smoking were 1.02 (95% confidence interval, 0.86 to 1.21) for CKD progression and 1.86 (95% confidence interval, 1.54 to 2.24) for all-cause mortality. Compared with nondrinking throughout follow-up, multivariable-adjusted hazard ratios for persistent alcohol drinking were 1.06 (95% confidence interval, 0.88 to 1.29) for CKD progression and 0.73 (95% confidence interval, 0.58 to 0.91) for all-cause mortality. Compared with nonuse throughout follow-up, multivariable-adjusted hazard ratios for persistent marijuana use were 0.94 (95% confidence interval, 0.82 to 1.07) for CKD progression and 1.11 (95% confidence interval, 0.96 to 1.30) for all-cause mortality. Compared with nonuse throughout follow-up, multivariable-adjusted hazard ratios for persistent hard illicit drug use were 1.25 (95% confidence interval, 1.00 to 1.55) for CKD progression and 1.41 (95% confidence interval, 1.10 to 1.81) for all-cause mortality.ConclusionsHard illicit drug use is associated with higher risk of CKD progression and all-cause mortality, tobacco smoking is associated with higher risk of all-cause mortality, and alcohol drinking is associated with lower risk of all-cause mortality among patients with CKD.

Dataset Information

The role of GABRA2 in alcohol dependence, smoking, and illicit drug use in an Australian population sample.

Publications

The role of GABRA2 in alcohol dependence, smoking, and illicit drug use in an Australian population sample.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets