Layla Sirag #ASHG22: GWAS have found thousands of common genetic variants associated with common diseases. Functional evaluation of these have been harder, especially since many are noncoding.
Layla Sirag #ASHG22: Even with an association, finding the causal variant is hard. Fine-mapping gives variants a posterior inclusion probability (PIP) that identifies a smaller set of likely causal variants.
Would be great to test every possible nucleotide, but likely impossible
Would be great to test every possible nucleotide, but likely impossible
Layla Sirag #ASHG22: Here, testing fine-mapped variants for function with a massively parallel reporter assay. Using 6 cell lines to represent different tissues. Looking for impacts on gene expression or allelic skew.
Layla Sirag #ASHG22: 300k variants tested -- 148k eQTLs, 78k complex trait variants, and 85k controls. Using eQTLs from GTEX and complex trait variants from UKB.
Found ~22k emVars [impacting allelic skew I believe].
Found ~22k emVars [impacting allelic skew I believe].
Layla Sirag #ASHG22: Promoters and multi-tissue effects are enriched in emVars. Also see some CTCF enrichment.
Differential sets of transcription factors are enriched for emVars vs enriched for high PIP variants.
Differential sets of transcription factors are enriched for emVars vs enriched for high PIP variants.
Layla Sirag #ASHG22: emVars break occupied motifs (bigger gap with more functional evidence).
Also find that 18% of the pairs of variants have some kind of interaction effects. Showing an example of a pair of variants near each other [but I missed the gene].
Also find that 18% of the pairs of variants have some kind of interaction effects. Showing an example of a pair of variants near each other [but I missed the gene].
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