This previously established association between rs9804190 and decreased expression led us to hypothesize that facets of psychopathology in humans corresponding to the behavioral phenotype observed in mice with reduced expression of Ank3 brain-specific isoforms (Leussis et al., 2012a) might be associated with rs9804190 genotype. We obtained nominally significant evidence of association between this expression-associated SNP and two characteristics implicated by the mouse study: externalizing and PTSD (p= 0.028 and p=0.042). The direction of association was as expected based on the prior association between rs9804190 and bipolar disorder, schizophrenia, and ankyrin G expression, and the behavioral changes in Ank3 mice. That is, the minor T allele, which was associated with higher ankyrin G expression and lower risk of bipolar disorder and schizophrenia, was here associated with reduced frequency of PTSD and less externalizing psychopathology. Conversely, the rs9804190 C allele linked to lower ankyrin G expression was associated with higher frequency of PTSD and a greater degree of externalizing behaviors, which corresponds to the heightened reactivity to stressors and increased behavioral disinhibition observed in mice with reduced ankyrin G expression.
