Genetic influences on alcohol sensitivity: A critical review.

Purpose of review: The present review provides a summary of the progress that genome-wide association studies (GWAS) have made in identifying the genetic variants that underlie the heritability of alcohol use disorder (AUD) and then provide a similar summary of alcohol sensitivity studies, an important endophenotype that can help to expand our understanding of the genetic architecture of AUD. Recent findings: GWAS of AUD have recently achieved the necessary sample sizes required to identify genome-wide significant risk loci and demonstrated that the disorder is genetically complex with many loci of small effect contributing to its etiology. Consequently, we describe how these studies have begun to explore AUD's genetic correlations with other alcohol-related traits and with other psychiatric disorders to better understanding the genetic etiology of AUD and its underlying mechanisms.GWAS investigating alcohol sensitivity using the Self-Rating of the Effects of Alcohol (SRE) as an AUD endophenotype have struggled to make similar progress. We describe the advances that these studies have made in terms of further demonstrating the heritability of alcohol sensitivity along with limitations in terms of identifying genome-wide significant loci and what we see as the primary challenges facing such studies. We conclude with suggestions for future research and what could be achieved with larger samples. Summary: Progress in the molecular genetic study of AUD and related phenotypes is being made. Nonetheless, significant efforts are needed to conduct GWAS of more specific AUD risk factors, such as alcohol sensitivity, to more fully understand how individual genetic loci contribute to AUD risk. In doing so, we will be better positioned to understand the etiologic relations between these AUD risk factors and how their confluence ultimately increases risk for AUD.