Several additional SNPs at p value of p < 10–4 in the combined sample were noted including one in GATA4 (see Fig. 1 and Table 3). GATA4 encodes the GATA Binding Protein 4, a member of the GATA family of zinc-finger transcription factors. Members of this family recognize the GATA motif which is present in the promoters of many genes and is thus an important cellular transcription regulator. GATA4 binds regulatory genomic regions of the atrial natriuretic peptide (ANP) receptor which are highly expressed in the amygdala, caudate and hypothalamus (Cao and Yang, 2008; Grepin et al., 1994). ANP is produced and released during alcohol withdrawal and may be anxiolytic by inhibition of corticotrophin releasing factor (CRF), adrenocorticotrophic hormone (ACTH) and cortisol (Antoni et al., 1992). A previous study found a significant association between GATA4 with alcohol dependence, relapse risk and treatment response with acamprosate (Kiefer et al., 2011). A follow-up study also reported an association between GATA4 genotype and limbic gray matter volume which was predictive of an increased risk for alcohol relapse (Zois et al., 2016). Thus, GATA4
