The genetics of alcohol-related liver disease

Significant advances into the genetics of alcohol-related liver disease (ALD) have been made in the last two decades. Most notably, this includes the discovery of ten common genetic variants associated either with alcohol-related cirrhosis and/or hepatocellular carcinoma. These novel associations provide insight into the pathophysiology of ALD and have led directly to potentially new therapeutic targets, which are the subject of ongoing research. In addition, several genetic risk scores are now available to identify patients at high/low risk of developing cirrhosis, albeit their performance may not yet be adequate to enable risk stratification in the clinic. Prospectively, the increasing accessibility of population-level biobank data together with the emergence of whole genome sequencing data will likely lead to further discoveries in the years ahead. In this chapter, we will review the key genetic association studies performed so far in relation to ALD, discuss the potential clinical applications, and identify areas worthy of future research.