Linkage disequilibrium (LD) is a major confounding factor that limits fine-scale discrimination among physically linked candidates in a QTL. To further evaluate the two high-priority candidates in Qrr1d—Fmn2 and Rgs7—we implemented a partial correlation analysis [68] in which the effect of genotype at Qrr1d was controlled. For this analysis, we computed the partial correlation coefficient between cis-regulated transcripts and each trans-regulated transcript after regression against the Qrr1d genotype. This partial correlation reveals residual variance that links cis candidates with trans targets, independent of genetic variance at Qrr1d. We computed the partial correlation between Rgs7 and Fmn2, and 14 transcripts representative of the different GOs that map to Qrr1d (dataset S4). The highest partial correlations are between Fmn2 and Rnf6 (r = 0.68, p-value<10−13), Atf4 (r = 0.6, p-value<10−9), Asns (r = 0.55, p-value<10−7), Ube2d3 (r = 0.5, p-value<10−6), Hnrpk (r = 0.5, p-value = 10−5), Rab2 (r = −0.5, p-value = 10−5), and Gars (r = 0.5, p-value = 10−5). The strongest correlate of Fmn2 is Rnf6, a gene involved in regulating actin dynamics in axonal growth cones [69]. Although not unequivocal, this analysis provides stronger support for Fmn2 than for Rgs7.
