Overview of the Genetics of Alcohol Use Disorder.

AIMS: Alcohol Use Disorder (AUD) is a chronic psychiatric illness characterized by harmful drinking patterns leading to negative emotional, physical, and social ramifications. While the underlying pathophysiology of AUD is poorly understood, there is substantial evidence for a genetic component; however, identification of universal genetic risk variants for AUD has been difficult. Recent efforts in the search for AUD susceptibility genes will be reviewed in this article. METHODS: In this review, we provide an overview of genetic studies on AUD, including twin studies, linkage studies, candidate gene studies, and genome-wide association studies (GWAS). RESULTS: Several potential genetic susceptibility factors for AUD have been identified, but the genes of alcohol metabolism, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), have been found to be protective against the development of AUD. GWAS have also identified a heterogeneous list of SNPs associated with AUD and alcohol-related phenotypes, emphasizing the complexity and heterogeneity of the disorder. In addition, many of these findings have small effect sizes when compared to alcohol metabolism genes, and biological relevance is often unknown. CONCLUSIONS: Although studies spanning multiple approaches have suggested a genetic basis for AUD, identification of the genetic risk variants has been challenging. Some promising results are emerging from GWAS studies; however, larger sample sizes are needed to improve GWAS results and resolution. As the field of genetics is rapidly developing, whole genome sequencing could soon become the new standard of interrogation of the genes and neurobiological pathways which contribute to the complex phenotype of AUD. SHORT SUMMARY: This review examines the genetic underpinnings of Alcohol Use Disorder (AUD), with an emphasis on GWAS approaches for identifying genetic risk variants. The most promising results associated with AUD and alcohol-related phenotypes have included SNPs of the alcohol metabolism genes ADH and ALDH.

Genome-wide association study of treatment response to venlafaxine XR in generalized anxiety disorder.

We conducted the first genome-wide association study (GWAS) in Generalized Anxiety Disorder (GAD) to identify potential predictors of venlafaxine XR treatment outcome. Ninety-eight European American patients participated in a venlafaxine XR clinical trial for GAD, with Hamilton Anxiety Scale (HAM-A) response/remission at 24 weeks as the primary outcome measure. All participants were genotyped with the Illumina PsychChip, and 266,820 common single nucleotide polymorphisms (SNPs) were analyzed. Although no SNPs reached genome-wide significance, 8 SNPs were marginally associated with treatment response/remission and HAM-A reduction at week 12 and 24 (p<0.00001). Several identified genes may indicate markers crossing neuropsychiatric diagnostic categories.