MD which best tag the overall associated SNPs on 12q21.31 for European populations, rs1545843 and rs1031681 (tab. 1). We tested the allelic and both alternative recessive-dominant genetic models of rs1545843 and rs1031681 and each probe and applied Bonferroni correction for the number of performed statistical tests. Both SNPs showed association only with the hippocampal expression of the full-length mRNA isoform of SLC6A15 reaching experiment-wide significance under a recessive model of inheritance (AA vs. AG+GG: rs1545843: p=4.3e-04, corrected p=1.8e-02, and rs1031681: p=1.4e-04, corrected p=6.6e-03, N=137). Risk genotype carrier status was associated with less SLC6A15 transcript (fig. 4A and B). These associations were supported by data from lymphoblastoid cell lines from the HapMap individuals where expression of the full-length SLC6A15 transcript was lower in carriers of the depression risk genotypes (fig. S3) and in an expression data set from peripheral blood monocytes (Heinzen et al., 2008) but not in a frontal cortex expression study (Myers et al., 2007), likely due to the lower expression of this gene in this brain region. Thus, gene expression experiments, including hippocampus expression, point towards an effect of the associated locus on SCL6A15 expression via long-range regulatory mechanisms (van Heyningen et al., 2006).
