The ANKK1/DRD2 locus is a genomic substrate for affective priming and recognition of angry faces

Abstract

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.

Regulatory rare variants of the dopaminergic gene ANKK1 as potential risk factors for Parkinson’s disease

“…The ANKK1 gene and protein have been related to the dopaminergic system 12 – 14 . In silico analysis of the A NKK1 locus identified share haplotypic blocks with the neighbor gene DRD2 (Dopamine Receptor D2 gene) 15 and it has been proposed that ANKK1 / DRD2 locus is a genomic substrate for cognitive traits 16 . Taq IA ANKK1 SNV is in linkage disequilibrium with DRD2 variants that regulate the expression of the long and the short isoforms of the DRD2 17 and its distribution in the ventral striatum 18 .…”

Ankyrin Repeat and Kinase Domain Containing 1 Gene, and Addiction Vulnerability

“…The genes that comprise the NTAD cluster show a conserved synteny and neighborhood in 22 vertebrate species using available databases [93]. In patients with addictions and healthy controls, the study of haplotypes within this cluster shows high linkage disequilibrium, haplotypes shared by several genes, and some SNVs in one gene that are also markers of another gene [73]. From a genetic perspective, these findings suggest the functional coordination of the proteins coded by genes of this cluster.…”

“…On the one hand, ANKK1 is adjacent to the DRD2 gene [21], shares haplotypic blocks and their promoters have cis elements in common for transcriptional regulation [17,73]. Additionally, TaqIA is in linkage disequilibrium with DRD2 variants that regulate the expression of long and short D2R isoforms [73,74], and modulates D2R distribution in the ventral striatum [75]. TaqIA A1 allele has also been associated with increased activity of striatal L-amino acid decarboxylase, the final enzyme for dopamine synthesis [76].…”

“…The ANKK1/DRD2 locus has another SNV associated with brain dopaminergic functions that consists of a C to T synonymous change within exon 7 of the DRD2 gene [77]. This SNV named C957T (rs6277) has a marked impact on D2R availability [78] and it is also a marker of regulatory regions at the 5 UTR of the ANKK1 gene [73]. In a sample of alcoholic patients, we found an epistatic effect of the ANKK1 TaqIA and DRD2 C957T SNVs on the expression of antisocial traits [79].…”

“…Therefore, it seems that ANKK1 and DRD2 genes could somehow interact with the dopamine signaling pathways or act in a coordinated manner, affecting individual vulnerability to both addictions and antisocial disorder. The ANKK1/DRD2 locus has also been related to cognitive and emotional processes [73,80] that could be associated with risk for developing addictions. A recent systematic review and meta-analysis evaluated the association of ANKK1 TaqIA and DRD2 C957T SNVs in the performance of the executive functions in healthy adults [81].…”