The question of genetic heterogeneity as a function of sample ascertainment has not been explicitly tested, but the emerging literature in this area suggests an imperfect correspondence between the genetic influences on alcohol use behaviors across populations. For example, while alcohol metabolism genes show reliable associations across multiple alcohol-related phenotypes in multiple samples, other genes/genetic variants have not replicated across clinical case-control samples (Hart and Kranzler, 2015) and population-based studies of alcohol consumption (Schumann et al., 2016) and problems (Sanchez-Roige et al., 2017). Hansell et al. (2009) have previously found evidence for differences in genetic associations for alcohol outcomes between unselected samples versus participants ascertained for a family history of AUDs. Further, the genetic correlations between alcohol consumption and problems, and between alcohol phenotypes and other psychiatric traits, show different patterns in general population samples (Sanchez-Roige et al., 2017) and in ascertained case-control studies like the Psychiatric Genomics Consortium (Walters et al., in preparation). The aim of the present study was thus to investigate whether there may be differences in the genetic liability for alcohol problems across two sample types:
