A cognitive phenotype for a polymorphism in the nicotinic receptor gene CHRNA4

Drawing on converging behavioral, electrophysiological, and imaging evidence, we advance an hypothesis for a cognitive phenotype of a SNP in the CHRNA4 gene encoding the α4 subunit of α4β2 nicotinic receptors. First, we review evidence that visuospatial attention can be decomposed into several component processes. Secondly, we consider evidence that one component, redirection of attention, is modulated by the nicotinic cholinergic system. Third, we review evidence that nicotinic stimulation exerts effects at the network level. Fourth, we consider evidence that normal variation in this SNP exerts nicotine-like modulatory effects on visuospatial attention. Fifth, we hypothesize that the cognitive phenotype of the CHRNA4 rs1044396 SNP is characterized by greater ability of T allele carriers to preferentially process events in the attentional focus compared to events outside the attentional focus. Finally, we consider effects of the CHNRA4 rs1044396 SNP on brain activity and cognition in light of our hypothesized cognitive phenotype. This hypothesis makes an important contribution to the development of cognitive phenomics by arguing for a cognitive phenotype of CHRNA4.

► We propose a cognitive phenotype of the CHRNA4 gene encoding α4 of α4β2 nAChRs. ► We hypothesize the CHRNA4 rs1044396 SNP influences focusing visuospatial attention. ► T allele carriers focus visuospatial attention more effectively on target events. ► This SNP is associated with unusually substantial evidence of a cognitive phenotype.