Thread by @thatdnaguy

#ASHG21 MO: Meritxell Oliva.
Genetic regulation of DNA methylation across tissues reveals thousands of molecular links to complex traits.

#ASHG21 MO: GTEx looks at gene expression, regulation, and its relationship to genetic variation. The v8 set has eQTL data. 15,201 RNA-Seq samples from 838 post-mortem donors. 49 tissues.

#ASHG21 MO: A mQTLs are variants associated with DNA methylation. GWAS-QTL colocalization can help prioritize the causal genes at a GWAS locus.

#ASHG21 MO: enhanced GTEx project eGTEx added additional studies. telomere length, ATAC, ChIP, methylation, RNA methylation, etc.

#ASHG21 MO: Look for mQTLs and how it contributes to eQTLs.
Preprint - researchsquare.com/article/rs-492…

#ASHG21 MO: Looked for cis mQTLs in a 500kb window to alleles. 100k-200k mQTL CpG sites per tissue.

#ASHG21 MO: mQTLs tended to dichotomize. Either very tissue specific, or highly shared across different tissues.

#ASHG21 MO: Used pair-wise colocalization to see what the overlap was between mQTL and eQTL. 21% of mQTLs are colocalized to an eQTL., i.e. most eQTLs are not explained by a cis-colocalized mQTL.

#ASHG21 MO: Look at mQTL mechanisms to eQTLs. eQTLs are enriched in gene body and proximal regulatory elements. mQTLs are enriched in non-genic, distal regulatory regions.

#ASHG21 MO: mQTLs are linked to transcription factors involved in chromatin spatial conformation and long-range interaction. eQTLs linked to TFs involved in basal transcription.

#ASHG21 MO: GWAS for 87 traits for 8.6M variants. Looked at colocalization. 12,922 QTL-GWAS colocalizations. 81% of the GWAS study had at least one. 41% of GWAS hits overall had colocalization. 3,381 mQTLs.

#ASHG21 MO: mQTL specific cases are traits colocalized with only an mQTL, but not to an eQTL. How does that work if the expression isn't changed?

#ASHG21 MO: eQTL and mQTL colocalizations can help with fine mapping GWAS signals. May also help with identifying independent SNP effects in the same locus.

#ASHG21 MO: at TERT, mQTL in ovary colocalizes with breast cancer GWAS signal. TERT expression is undetectable in normal ovary. Expressed in stem and stem-like cells.