Unlike Mendelian disorders such as cystic fibrosis or Huntington’s disease, where a mutation in a single gene is sufficient to cause disorder, the pathway from genotype to phenotype for alcohol outcomes is not necessarily straightforward. Alongside advances in characterizing genetic risk, research has suggested that a number of environmental factors can alter the importance of genetic influences on alcohol outcomes (Young-Wolff et al., 2011), and it has also been suggested that G×E effects may harbor some of the ‘hidden heritability’ for complex behavioral outcomes (Manolio et al., 2009). Despite strong evidence for G×E effects from twin studies (Young-Wolff et al., 2011), the study of G×E using measured genotypes has been controversial (Duncan and Keller, 2011, Dick et al., 2015).
