This study examined the relationship of ANK3, a gene previously associated with risk of bipolar disorder, schizophrenia, and other psychiatric-related traits, to PTSD and a variable reflecting the common externalizing factor underlying adult antisociality, as well as substance abuse/dependence symptoms. We began by focusing our attention on rs9804190 because it has been associated previously with both bipolar disorder and ankyrin G expression in human brain (Baum et al., 2008; Roussos et al., 2012; Schulze et al., 2009; Sklar et al., 2011) and was available in the genome-wide SNP data from our sample. Specifically, in a sample of schizophrenia postmortem brains, Roussos et al. (Roussos et al., 2012) found lower ankyrin G expression in superior temporal gyrus was associated with the rs9804190 CC genotype (C is the major allele associated with bipolar disorder risk; (Schulze et al., 2009)). Further, the rs9804190 C allele was associated with the presence of schizophrenia in the postmortem sample (p=0.03 in n=208 cases and n=64 controls) and with performance on schizophrenia-related tests of cognition and memory in healthy (without schizophrenia) subjects. The authors suggested that variants in ANK3 affecting ankyrin G expression represent a causal mechanism by which ANK3 contributes to schizophrenia risk.
