Although AUD is known to be moderately heritable, the search for genetic vulnerability factors has proven to be more difficult than originally thought and to date only a small proportion of the genetic variance has been accounted for. Over the past decade there have been tremendous advances in large scale SNP genotyping technologies and next generation sequencing, and these technologies, including GWAS arrays and whole genome sequencing, are now widely available. Results of GWAS suggest that numerous common variants with very small effect are likely to encode proteins within, or regulate, numerous biological pathways. However, GWAS findings have to date explained only a small portion of the genetic vulnerability to AUD, in part because many studies have been underpowered. Another explanation for the ‘missing heritability’ of AUD may be that there are rare variants clustered within genes or pathways that in aggregate yield large effects. The new technologies may help to unravel the complex genetics of AUD, a crucial advance in order to improve prevention and to develop, through molecular diagnostic methods, more effective, individually-targeted pharmacotherapies.
