Thread by @thatdnaguy

#ASHG21 OEG: Omar El Garwany.
Genetic determinants of alternative splicing in stimulated iPSC-derived macrophages enhance the understanding of immune-mediated disease risk.
@oelgarwany

@oelgarwany #ASHG21 OEG: macrophages respond quickly to environmental stimuli, and these stimuli may cause substantial changes to their gene expression.

#ASHG21 OEG: QTLs are context-specific. May require not just the right cell type (macrophages), but the right stimulation (environmental condition).

#ASHG21 OEG: MacroMap study. eQTL and sQTL maps in macrophages. Going to talk about splicing QTLs. Use leafcutter and QTLtools.
github.com/davidaknowles/…
github.com/qtltools/qtlto…

#ASHG21 OEG: ~5,500 genes with significant splicing QTL effects in macrophages under different conditions.

#ASHG21 OEG: Wanted to understand the relationship between splicing and expression QTLs. about 0.6 fraction of splice QTLs are eQTLs.

#ASHG21 OEG: Stimulating macrophages increases the number of splice QTL genes colocalized with GWAS significant loci.

#ASHG21 OEG: About 20% of GWAS loci colocalize with eQTL. 43% colocalize with sQTLs. [ !!! ]

#ASHG21 OEG: sQTLs that localize with IBD risk loci are in the stimulated macrophages on. No colocalization with eQTL in naive or stimulated.

#ASHG21 OEG: DENND1B in IBD. a stimulation-specific sQTL may underlie an IBD GWAS signal near this gene.