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Chunk #36 — Discussion

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Brain expression quantitative trait locus and network analyses reveal downstream effects and putative drivers for brain-related diseases.
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The analyses identified trans-eQTLs in the brain cortex for many variants, some of which are brain-specific. Similar to blood, the trans-eQTL-effect sizes in the brain were usually small, emphasizing the importance of increasing the sample size of brain eQTL studies. The identified trans-eQTLs allowed us to gain insights into the functional effect of several disease-associated variants. We observed that trans-eQTL SNPs were enriched for cis-eQTL index SNPs, indicating consequences beyond the gene regulated in cis. Our trans-eQTL analysis focused on a single brain region and was limited to trait-associated and cis-eQTL SNPs. We expect that a genome-wide approach will identify many more trans-eQTLs. Furthermore, we note that true separation of cis- and trans-eQTL effects would require investigation of the allelic function of the associated SNPs (Supplementary Note).