Most candidate genes selected for AUD genetic association studies can broadly be divided into two categories: 1) genes involved in central nervous system’s (CNS) response to alcohol or other addictive substances (CHRNA5, GABRG1, GABRA2, OPRM1 etc.)[27, 31–35] and 2) genes involved in alcohol metabolism (ADH4, ADH1B, ALDH2)[36–41]. Out of all candidate genes, role of ADH1B in AUD is very well established and replicated, particularly among populations of Asian descent[36, 37, 42]. However, variants in ADH1B are uncommon (~3–5%) in European Americans (EAs) and African Americans (AAs) [36]. This is the reason that a low frequency coding variant of ADH1B gene (rs1229984) was originally identified in Asian samples and was subsequently replicated in EAs and AAs in a large meta-analysis[36]. This single nucleotide change leads to replacement of Arg48 with His48 and results in a “atypical ADH” enzyme that exhibits several times higher catalytic activity than the normal enzyme. Increased accumulation of acetaldehyde from due to higher catalytic activity of “atypical ADH” is responsible for the flushing and severe symptoms of alcohol related sensitivity[37, 40]. The intense aversive reaction to even
