Among those 220 eQTLs having either an SV-eQTL or an SV in LD with the lead SNP/indel, most were due to deletions (55% of associations), followed by mCNVs (19%) (Supplementary Table 8). Although SV-eQTLs with the largest effect sizes tended to overlap with CDSs, such as for the dual specificity phosphatase 22 (DUSP22) gene (Fig. 2c), we also observed several expression-associated SVs strictly intersecting upstream noncoding sequences, including an mCNV upstream of ZNF43 (Fig. 2d) possibly mediated through variation of a cis-regulatory element. We additionally considered the impact of accounting for SVs when constructing personalized reference genomes for transcriptome analysis. To illustrate this, we considered RNA read alignments for the sample NA12878, comparing the standard reference genome with GRCh37-derived personalized references constructed using NA12878 SNPs, or using NA12878 SNPs and SVs. Using such an approach, we observed marked changes in expression for 525 exons (±10 reads, ≥onefold change relative to the standard reference), 24 of which could be attributed to the inclusion of SVs into the personalized reference (Supplementary Table 9).
