Recently, CRHBP has gained prominence as a candidate gene for stress-related disorders (Binder et al., 2010; De Luca et al., 2010; Enoch et al., 2008; Kertes et al., 2010; Ray, 2011). Three of these studies (Binder et al., 2010; De Luca et al., 2010; Kertes et al., 2010) also investigated CRH, CRHR1 and CRHR2 SNPs but found significant results only for CRHBP. Our study participants were African Americans, many of whom had been diagnosed with substance dependence, a known risk factor for suicidal behavior (Roy, 2001, 2002, 2003; Roy and Janal, 2007). We previously showed that childhood trauma predicted suicidality in this sample (Roy et al., 2010). Based upon the results of the studies described above, we hypothesized that CRHBP variation and also the interaction with childhood trauma might influence suicidal behavior. We further hypothesized that we would find phenotype associations with distal CRHBP SNPs since all five of the earlier studies found associations only within this region of the gene. For the sake of completeness we also analyzed the effects of variation in CRH, CRHR1 and CRHR2, but expected negative results based on the earlier findings.
