paperKB
coga / coga-kb
Help
Sign in

Chunk #28 — Discussion

Source
Brain expression genome-wide association study (eGWAS) identifies human disease-associated variants.
Embedded
yes

Text

Third, there is remarkable replication of significant cisSNP associations across different brain regions and underlying tissue pathologies. Indeed, the 2,980 top cerebellar cisSNP/transcript associations represent 58% and 68%of all significant associations in the ADs and non–ADs. Since >50% of the non–ADs were comprised of subjects with PSP, we also conducted a separate analysis of this pathologically distinct group of non–ADs and again determined that many of the top cisSNPs were also significant in the PSPs despite the small sample size (n = 98). Importantly, most of the cisSNPs had highly similar effect sizes in the ADs, non–ADs and PSP subset of non–ADs. Furthermore, 78% of the top cerebellar cis-associations were also significant in the temporal cortex. Cerebellum is a relatively unaffected region in AD, whereas temporal cortex is typically one of the first areas to harbor neuropathology [51]. It is not inherently evident whether the unaffected or affected tissue regions would be most suitable for eQTL studies. Whereas unaffected regions would have the advantage of minimizing confounding on expression measurements from pathology (such as inflammation and cell death), affected regions