The slow progress in gene identification at both the individual variant level and the aggregate polygenic level is likely due in part to the heterogeneous pathways by which many different individuals develop alcohol problems, even though alcohol problems are typically classified in research by a single binary case-control diagnostic status for AUD (Hart and Kranzler, 2015). AUDs have numerous and heterogeneous demographic predictors (Grant et al., 2015), and a long history in the literature suggests that there are multiple “types” of alcoholism that display different epidemiological patterns and may represent divergent syndromes despite their shared symptoms (Leggio et al., 2009; Babor et al., 1992; Cloninger et al., 1988). An AUD diagnosis is itself a constellation of many possible subsets of symptoms that fall under both the physical (e.g. tolerance; withdrawal) and psychosocial (e.g. impairments in work and social functioning) domains, and some evidence suggests that distinct genetic factors underlie different symptom clusters (Kendler et al., 2012). The development of AUDs may thus be driven in different groups of individuals by distinct physiological and/or psychological factors whose genetic etiologies are not perfectly overlapping (Hines et al., 2005).
