Importantly, rs1409568 is predicted to bear active enhancer marks in several brain-derived tissues that are critical to addiction, most notably the dlPFC and the cingulate and angular gyri, which play a major role in the development of addictive behaviors, particularly in the regulation of executive control and attentional bias (57). These in-silico findings imply that the C allele is associated with reduced or no binding of several homeodomain-containing (58) developmentally relevant transcription factors, with some difference scores (e.g., POU6F2) being substantial (>8.0). These genes and their products have been variously implicated in embryogenesis and in cell-type specific pathways of differentiation, particularly in visual systems (59–61), but have not been related to behavioral traits thus far.
