Among nonsynonymous SNPs consistently meeting significance thresholds for association with alcohol dependence are those in the genes encoding alcohol dehydrogenase (ADH) and alcohol aldehyde dehydrogenase (ALDH) (Bierut et al., 2012; Edenberg, 2007; Sanchez-Roige et al., 2017), which have been previously identified through linkage analysis (Edenberg et al., 2006) and biochemistry (Smith et al., 1971; von Wartburg et al., 1965). These proteins play a key role in alcohol metabolism, and their variants have a profound effect on alcohol consumption in rodents and humans (Edenberg, 2007). Genetically dictated differences in metabolism, either due to ADH or ALDH function, indicate that liver function may contribute AUD manifestation (Smith et al., 1971; von Wartburg et al., 1965). Linkage analysis by COGA has also enabled fine mapping of targeted chromosomal regions (Wang et a. 2004). Eight SNPs associated with alcohol dependence (p<0.01) were identified, with four located near the ACN9 gene, which codes for a mitochondrial intermembrane protein of gluconeogenesis (Dick et al., 2008). Investigation of mitochondrial abnormalities in patient derived neurons containing these SNPs is a potential avenue of research. Additionally, patient-derived liver cells
