The largest GWAS to date with direct relevance to AUD is a meta-analysis effort, combining AUD per se (from MVP and the Psychiatric Genomics Consortium) and the alcohol use component of the AUDIT related to medical problems, i.e. the AUDIT-P (from the UK Biobank); the meta-analyzed trait was considered to be “problematic alcohol use (PAU)”. This study included 435,563 European-ancestry individuals and identified 29 independent risk variants (e.g., thrombospondin type 1 domain containing 7B (THSD7B) and cell adhesion molecule 2 (CADM2))13. In addition to the gene discovery, the large sample size permitted a much more powerful investigation of PAU polygenicity. For example, 138 significant genetic correlations with other traits were observed. Positive genetic correlations included major depression, depressive symptoms, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder, among psychiatric traits, as well as insomnia; negative correlations included subjective well-being and age of smoking initiation. With respect to physical health, phenome-wide association analysis with a polygenic risk score (PRS) for PAU implicated several disorders associated with alcohol and tobacco abuse, including alcoholic liver disease and chronic airway obstruction and bronchitis.
