Multiple causal variants underlie genetic associations in humans

We applied a massively parallel reporter assay (MPRA) in lymphoblastoid cells to functionally evaluate 49,256 allelic pairs, representing 30,893 genetic variants in high, local linkage disequilibrium for 744 independent cis-expression quantitative trait loci (eQTLs) assessed for colocalization across 114 traits. Overall design: We performed three independent transfections of our MPRA library into GM12878 cells by electroporation and recovered RNA after 24 hours. We quantified barcode counts in the cDNA samples as well as the plasmid pool by single-end Illumina sequencing. Barcodes mapping to the same oligo in the oligo pool were summed to generate raw oligo counts and aggregated across replicates.