Interestingly, the brain-wide expression pattern of DHRS11 and ISM1 are highly correlated with the expression of several of the other genes found among the top hits of both the case-control and the trio-case-control meta-analyses (www.BrainSpan.org, Release 3) (Supplementary Figure S12).66 Furthermore, many of these genes have been implicated in glutamate signaling. Specifically, ISM1 (C20orf82) is correlated with expression of pre-synaptically-located ADCY8 (0.61, rank 11 of 22,328 transcripts), the gene with the seventh strongest OCD-association in the trio-case-control meta-analysis, which has also been associated with bipolar disorder67 and with fear memory.68 ISM1 is also correlated with brain-wide expression of numerous glutamate-related genes including GRIK4 (0.565, rank 66), DLGAP3 (0.576,rank 44), GRIK1 (0.595,rank 22), SHANK3 (0.598,rank 21) as well as ADARB2 (0.600,rank 19), which contains the SNP with the best p-value in this study among previously reported candidate genes (Supplementary Table S4), and lies within a childhood-onset OCD linkage peak.22 Similarly, the expression of DHRS11 (MGC4172) is strongly correlated (0.847, rank 25 of 22,328 transcripts) with that of FAIM2, which is located in the same LD block as the best SNP (rs297941)
