The TaqIA single nucleotide variant (SNV) has been tested for association with addictions in a huge number of studies. TaqIA is located in the ankyrin repeat and kinase domain containing 1 gene (ANKK1) that codes for a receptor interacting protein kinase. ANKK1 maps on the NTAD cluster along with the dopamine receptor D2 (DRD2), the tetratricopeptide repeat domain 12 (TTC12) and the neural cell adhesion molecule 1 (NCAM1) genes. The four genes have been associated with addictions, although TTC12 and ANKK1 showed the strongest associations. In silico and in vitro studies revealed that ANKK1 is functionally related to the dopaminergic system, in particular with DRD2. In antisocial alcoholism, epistasis between ANKK1 TaqIA and DRD2 C957T SNVs has been described. This clinical finding has been supported by the study of ANKK1 expression in peripheral blood mononuclear cells of alcoholic patients and controls. Regarding the ANKK1 protein, there is direct evidence of its location in adult and developing central nervous system. Together, these findings of the ANKK1 gene and its protein suggest that the TaqIA SNV is a marker of brain differences, both in structure and in dopaminergic function, that increase individual risk to addiction development.

These data suggest that sensory information processing mechanisms could be damaged in abstinent alcoholic patients. The fact that these findings are common to other psychiatric disorders could indicate the existence of a common vulnerability marker and explain the high degree of comorbidity between alcoholism and other mental illnesses.

IntroductionAnkyrin repeat and kinase domain containing I (ANKK1) and dopamine D2 receptor (DRD2) genes have been associated with psychopathic traits in clinical samples. On the other hand, individuals high in psychopathy show reduced affective priming and deficits in facial expression recognition. We have hypothesized that these emotion‐related cognitive phenomena are associated with Taq IA (rs18000497) SNP (single nucleotide polymorphism) of the ANKK1 gene and with C957T (rs6277) SNP of the DRD2 gene.MethodsWe performed a genetic association analysis in 94 self‐reported Caucasian healthy volunteers. The participants completed 144 trials of an affective priming task, in which primes and targets were emotional words. They also had to recognize 64 facial expressions of happiness, sadness, anger, and fear in an expression recognition task. Regarding the genetic analyses, Taq IA and C957T SNPs were genotyped.ResultsWe found that the C957T SNP TT genotype was associated with a stronger priming effect and a better recognition of angry expressions. No associations were found for the Taq IA SNP. In addition, in silico analysis demonstrated that C957T SNP is a marker of a regulatory sequence at the 5′ UTR of ANKK1 gene, thus suggesting the involvement of the whole ANKK1/DRD2 locus in cognitive–emotional processing.ConclusionsThese results suggest that affective priming and recognition of angry facial expressions are endophenotypes that lie on the pathway between the ANKK1/DRD2 locus and some deviant phenotypes.