Evaluation of a structural polymorphism in the ankyrin repeat and kinase domain containing 1 (ANKK1) gene and the activation of executive attention networks

The specificity of genetic effects on brain activation is a central issue in understanding how molecular actions at the synapse relate to anatomic patterns of brain activity. In an effort to understand the basis for the specificity of gene-associated brain activity, we explore a well-studied genetic polymorphism, TaqIA, which lies downstream of the DRD2 gene in the protein-encoding region of a neighboring gene, ANKK1, which is not expressed in the brain. We utilize the attention network test and find that carriers of the A1 allele show gene-associated functional activation in an anatomically specific, dopamine-rich region of the brain comprising the anterior cingulate gyrus, a finding partially consistent with prior data from functional imaging genetics. A review of the patterns of expression for ANKK1 and DRD2 and the extent of linkage disequilibrium between the two genes sheds light on additional criteria for the selection of candidate genes in imaging-genetic studies.