The H4 haplotype, as detailed in Table 2, which was almost twice as common in those with OCD as in controls (odds ratio, 1.89), represents the strongest haplotypic association of SLC1A1 with OCD published to date.16-18 It illustrates the usefulness of our complementary expression–mining approach, because 2 of its markers were eQTLs, and conditional haplotypic association testing with the remaining markers failed to yield positive results (see the “Methods” section).28,32 The individual alleles in H4, however, are not fully compatible with the notion of increased or decreased SLC1A1 gene expression in OCD, as the C allele at rs7858819 was the lower-expressing allele in the regression analyses (Figure 1B), while the C allele at rs301430 in H4 correlated with increased expression (Table 2 and Figure 1). On the other hand, the mildly protective haplotype H2 in Table 2 (odds ratio, 0.78), which narrowly survived correction for multiple testing in individual haplotype analysis, contained the lower-expressing allele at both eQTLs. Here, too, it will be essential to conduct gene expression analyses in larger samples and with more densely spaced markers.
