Dataset Information

Alcohol Dependence Genetics: Lessons Learned From Genome-Wide Association Studies (GWAS) and Post-GWAS Analyses.

ABSTRACT: Alcohol dependence (AD) is a complex psychiatric disorder and a significant public health problem. Twin and family-based studies have consistently estimated its heritability to be approximately 50%, and many studies have sought to identify specific genetic variants associated with susceptibility to AD. These studies have been primarily linkage or candidate gene based and have been mostly unsuccessful in identifying replicable risk loci. Genome-wide association studies (GWAS) have improved the detection of specific loci associated with complex traits, including AD. However, findings from GWAS explain only a small proportion of phenotypic variance, and alternative methods have been proposed to investigate the associations that do not meet strict genome-wide significance criteria.This review summarizes all published AD GWAS and post-GWAS analyses that have sought to exploit GWAS data to identify AD-associated loci.Findings from AD GWAS have been largely inconsistent, with the exception of variants encoding the alcohol-metabolizing enzymes. Analyses of GWAS data that go beyond standard association testing have demonstrated the polygenic nature of AD and the large contribution of common variants to risk, nominating novel genes and pathways for AD susceptibility.Findings from AD GWAS and post-GWAS analyses have greatly increased our understanding of the genetic etiology of AD. However, it is clear that larger samples will be necessary to detect loci in addition to those that encode alcohol-metabolizing enzymes, which may only be possible through consortium-based efforts. Post-GWAS approaches to studying the genetic influences on AD are increasingly common and could greatly increase our knowledge of both the genetic architecture of AD and the specific genes and pathways that influence risk.

SUBMITTER: Hart AB

PROVIDER: S-EPMC4515198 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Alcohol Dependence Genetics: Lessons Learned From Genome-Wide Association Studies (GWAS) and Post-GWAS Analyses.

Hart Amy B AB Kranzler Henry R HR

Alcoholism, clinical and experimental research 20150625 8

<h4>Background</h4>Alcohol dependence (AD) is a complex psychiatric disorder and a significant public health problem. Twin and family-based studies have consistently estimated its heritability to be approximately 50%, and many studies have sought to identify specific genetic variants associated with susceptibility to AD. These studies have been primarily linkage or candidate gene based and have been mostly unsuccessful in identifying replicable risk loci. Genome-wide association studies (GWAS) h ...[more]

PMID: 26110981

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Project description:ObjectivesGlobally, the burden of disease caused by alcohol use has been steadily increasing, including in Thailand. In this study, we aim to test the effectiveness of Anderson et al.'s suggested three approaches to change the collective social norms, which comprise of: (1) providing information and an understanding about alcohol use behaviour, its causes and distribution; (2) focusing strategies on groups rather than individuals; and (3) strengthening supportive laws, regulations and approaches.Study designWe employed a mixed-methods approach. Evidence was gathered from literature review and in-depth interviews with key individuals who are responsible for community-based interventions to alcohol marketing strategies in Thailand.MethodsWe chose to focus on two case studies in Nan and Surin provinces, where hospital-based longitudinal data (8 years) were available. Changes in casualties related to the harmful use of alcohol, resulting from interactions between community-based interventions and alcohol marketing during the time of annual festivals were investigated. We employed the theory of change (ToC) defined by Vogel to guide the data collection and analysis. We reviewed literature from online databases and grey literature to generate causal-loop diagrams.ResultsWe created a causal-loop diagram to describe the complexity of harmful alcohol use, its related factors, context, interventions and outcomes. Over the decade between 2006 and 2015, community-based strategies led to a substantial reduction of casualties (initially a 50% reduction, rising to an 80-90% reduction by the end of the study period) during the time of the festivals.ConclusionsThe reduction in injuries and fatalities could be a result of the concerted actions, including legal sanctions of alcohol beverage sales and advertisement, and public education to raise awareness and impart knowledge of the harmful use of alcohol. The actions were organised by a coalition of civil society, health professionals, public authorities and community leaders using hospital-based data on the adverse effects of harmful alcohol use to mobilise political support at the provincial level. The availability of long-term financial support as a catalytic source of funds and the presence of a comprehensive alcohol control act enabled framing and mobilisation of local resources and political support.

Dataset Information

Alcohol Dependence Genetics: Lessons Learned From Genome-Wide Association Studies (GWAS) and Post-GWAS Analyses.

Publications

Alcohol Dependence Genetics: Lessons Learned From Genome-Wide Association Studies (GWAS) and Post-GWAS Analyses.

Similar Datasets

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