While the available data did not allow us to test the entire TAT haplotype reported by Bradley et al. (2008) and Kranzler et al. (2011) as a moderator of the effect of adverse childhood experiences on lifetime risk of major depression, our findings are consistent in suggesting a G × E effect for this common region of the CRHR1 gene. Our study has shown that the rs110402 and rs242924 SNPs were driving the block 1 haplotype analyses and that the major alleles of these two SNPs are protective against risk of AD in trauma exposed individuals but conversely increase risk for AD in individuals who have not experienced adulthood trauma. The direction of these findings is opposite to earlier studies showing that the TAT haplotype, including the minor alleles of rs110402 and rs242924, was protective against major depression in African Americans and Caucasians exposed to childhood trauma (Bradley et al., 2008, Kranzler et al., 2011a). Moreover, Tyrka et al. (2009) showed that in individuals exposed to childhood trauma, carriers of the major homozygotes of rs110402 and rs242924 showed elevated cortisol response to the dexamethasone suppression test (Tyrka et al., 2009).
