To extract and evaluate intermediate molecular and genetic networks interposed between the Per3 polymorphism and higher order phenotypes, we extracted transcripts with trans QTLs that map to the Per3 locus in the neocortex (Figure 5). We found a set of 48 transcripts with likelihood ratio statistic scores above 10 that map near Per3 (nominal P<0.01). This set includes genes associated with RNA processing (Pabpc1, Rbm14, Rps11, Sfrs1 and Sfrs12), ion channel activity (Cacna1c, Trpm2 and Fxyd6) and synaptic function (Anks1b and Doc2a). We next asked if any of these 48 genes that are putatively trans-regulated by Per3 have functional associations with (1) circadian rhythm, (2) stress or (3) alcoholism. For this, we mined the literature for such associations using the Chilibot web resource (http://www.chilibot.net/).50 Four genes (Rbm14, Pabpc1, Irak2 and Il2rb) are associated with circadian rhythm, six genes (Trpm2, Erp29, Sepp1, Cacna1c, Smpd2 and Trim29) are associated with responses to physiological and cellular stress, two genes (Pdlim5 and Fxyd6) are associated with schizophrenia and one gene (Cast) is associated with alcoholism.
