Although the protective effects of moderate drinking are controversial, we found that alcohol consumption in the absence of genetic risk for AUD may protect from cardiovascular disease, diabetes mellitus, and major depressive disorder. In contrast, individuals with genetic risk for AUD are at elevated risk for some adverse secondary phenotypes, including insomnia, smoking, and other psychiatric disorders. However, individuals who have had health problems resulting from drinking are more likely to reduce or stop drinking by middle age or under-report their alcohol consumption. This offers an alternative explanation for the opposite genetic associations38, particularly in an older clinical sample in which a large proportion report current abstinence (reflected in an AUDIT-C score of 0). For this complex set of genetic associations to be useful in informing clinical recommendations on safe levels of alcohol consumption, it will be necessary to elucidate the mechanisms underlying these findings.
