Dataset Information

The association between DRD2/ANKK1 and genetically informed measures of alcohol use and problems.

ABSTRACT: In 1990, Blum and colleagues first reported an association between DRD2 and alcoholism. While there have been subsequent replications of this genetic association, there have also been numerous studies that failed to detect an association between DRD2 and alcohol dependence. We propose that one aspect contributing to this inconsistency is the variation in alcohol phenotype used across studies. Within the population-based Finnish twin sample, FinnTwin16, we previously performed multivariate twin analyses to extract latent genetic factors, which account for the variation across seven measures of alcohol consumption (frequency of drinking, frequency?×?quantity, frequency of heavy drinking, frequency of intoxication and maximum drinks in a 24-hour period) and problems (the Rutgers Alcohol Problem Index-RAPI and the Mälmö-modified Michigan Alcohol Screen Test-MmMAST) in 3065 twins. In the present study, we examined the association between 31 DRD2/ANKK1 single-nucleotide polymorphisms (SNPs) and the genetic factor scores generated by twin analyses in a subset of FinnTwin16 (n?=?602). We focus on two of the genetic factors: a general alcohol consumption and problems factor score, which represents shared genetic variance across alcohol measures, and a alcohol problems genetic factor score, which loads onto the two indices of problematic drinking (MAST and RAPI). After correction for multiple testing across SNPs and phenotypes, of the 31 SNPs genotyped across DRD2/ANKK1, one SNP (rs10891549) showed significant association with the general alcohol consumption and problems factor score (P?=?0.004), and four SNPs (rs10891549, rs1554929, rs6275, rs6279), representing two independent signals after accounting for linkage disequilibrium, showed significant association with the alcohol problems genetic factor score (P?=?0.005, P?=?0.005, P?=?0.003, P?=?0.003). In this study, we provide additional positive evidence for the association between DRD2/ANKK1 and alcohol outcomes, including frequency of drinking and drinking problems. Additionally, post hoc analyses indicate stronger association signals using genetic factor scores than individual measures, which suggest that accounting for the genetic architecture of the alcohol measures reduces genetic heterogeneity in alcohol dependence outcomes in this sample and enhances the ability to detect association.

SUBMITTER: Meyers JL

PROVIDER: S-EPMC3522787 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The association between DRD2/ANKK1 and genetically informed measures of alcohol use and problems.

Meyers Jacquelyn L JL Nyman Emma E Loukola Anu A Rose Richard J RJ Kaprio Jaakko J Dick Danielle M DM

Addiction biology 20120912 3

In 1990, Blum and colleagues first reported an association between DRD2 and alcoholism. While there have been subsequent replications of this genetic association, there have also been numerous studies that failed to detect an association between DRD2 and alcohol dependence. We propose that one aspect contributing to this inconsistency is the variation in alcohol phenotype used across studies. Within the population-based Finnish twin sample, FinnTwin16, we previously performed multivariate twin a ...[more]

PMID: 22970887

Similar Datasets

Project description:BackgroundGenetic factors are important in the pathogenesis of Tourette syndrome (TS). Notably, Dopamine receptor D2 (DRD2) gene has been suggested as a possible candidate gene for this disorder. Several studies have demonstrated that DRD2/ANKK1 TaqIA polymorphism is associated with an increased risk of developing TS. However, past results remain conflicting. We addressed this controversy by performing a meta-analysis of the relationship between DRD2/ANKK1 TaqIA polymorphism and TS.MethodsLiterature was searched in multiple databases including PUBMED, COCHRANE and WEB OF SCIENCE up to July 2014. The number of the genotypes for DRD2/ANKK1 TaqIA in the TS and control subjects was extracted and statistical analysis was performed using Review Manager 5.0.16 and Stata 12.0 software. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) were utilized to calculate the risk of TS with DRD2/ANKK1 TaqIA. Stratified analysis based on ethnicity was also conducted.Results523 patients with TS, 564 controls and 87 probands plus 152 relatives from five published studies were finally involved in this meta-analysis. Combined analysis revealed that the overall ORs for the DRD2/ANKK1 TaqIA A1 allele were 1.69 (95%CIs = 1.42-2.00) in the fixed-effect model and 1.66 (95%CIs = 1.33-2.08) in the random-effects model. Stratification by ethnicity indicated the TaqIA A1 allele was significantly associated with TS in Caucasians (fixed-effect model: OR=1.75, 95%CI = 1.43-2.16; random-effect model: OR=1.69, 95%CI = 1.25-2.28) and in Asians (OR=1.54, 95%CI = 1.12-2.10). Meta-analysis of the A1A1 vs. A2A2 (homozygous model), A1A2 vs. A2A2 (heterozygous model) and A1A1+A1A2 vs. A2A2 (dominant model) of this polymorphism revealed a significant association with TS in overall populations and Caucasians.ConclusionsThis meta-analysis suggested that the DRD2/ANKK1 TaqIA polymorphism might contribute to TS susceptibility, especially in Caucasian population. However, further investigation with a larger number of worldwide studies should be conducted to verify the association.

Project description:ObjectiveShort sleep duration and sleep problems increase risks of overweight and weight gain. Few previous studies have examined sleep and weight repeatedly over development. This study examined the associations between yearly reports of sleep problems and weight status from ages 5 to 11. Although, previous studies have shown that inter-individual differences moderate the effect of short sleep duration on weight, it is not known whether inter-individual differences also moderate the effect of sleep problems on weight. We tested how the longitudinal associations between sleep problems and weight status were moderated by impulsivity and genetic variants in DRD2 and ANKK1.DesignSeven-year longitudinal study.ParticipantsA total of 567 children from the Child Development Project for the analysis with impulsivity and 363 for the analysis with genetic variants.Measurements and resultsSleep problems and weight status were measured by mothers' reports yearly. Impulsivity was measured by teachers' reports yearly. Six single-nucleotide polymorphisms located in DRD2 and ANKK1 were genotyped. Data were analyzed using multilevel modeling. Higher average levels of sleep deprivation across years were associated with greater increases in overweight (P=0.0024). Sleep problems and overweight were associated at both within-person across time (P<0.0001) and between-person levels (P<0.0001). Impulsivity and two polymorphisms, rs1799978 and rs4245149 in DRD2, moderated the association between sleep problems and overweight; the association was stronger in children who were more impulsive (P=0.0022), in G allele carriers for rs1799978 (P=0.0007) and in A allele carriers for rs4245149 (P=0.0002).ConclusionsThis study provided incremental evidence for the influence of sleep problems on weight. Findings of DRD2, ANKK1 and impulsivity are novel; they suggest that reward sensitivity and self-regulatory abilities might modulate the influences of sleep on weight gain. The analysis of polymorphisms was restricted to European Americans and hence the results might not generalize to other populations.

Dataset Information

The association between DRD2/ANKK1 and genetically informed measures of alcohol use and problems.

Publications

The association between DRD2/ANKK1 and genetically informed measures of alcohol use and problems.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets