Based on their known brain expression patterns and potential biological relevance in the context of neuropsychiatric disorders, we elected to follow up six of the 25 putative miR-34a targets that overlap with genes within the BD GWAS loci: ANK3, CACNA1C, CACNB3, ODZ4, DDN, and KLC216, 43, 44, 55, 56. To further explore the putative miR-34a targets, we first checked the predicted binding site between the target mRNA and miR-34a using TargetScan (Table S2). Then, to experimentally validate the predicted miR-34a targets we needed to test whether the interaction sites between miR-34a and the mRNA targets are functional57, 58. Luciferase reporter assays revealed that miR-34a overexpression was capable of targeting and silencing the BD risk genes ANK3, DDN, and CACNB3 along with the previously shown target gene SYT127, but had no effect on the 3’UTRs of CACNA1C, ODZ4 and KLC2 (Figure 2A). In addition, global analysis of miR-34a predicted targets showed enrichment of molecular networks related to neuronal development, differentiation and synaptic plasticity as well as gene sets implicated in neurodevelopmental disorders (Tables S3–S742). Taken together, these results validate three genes
