Fig. 1

Use of MPRA to identify causal variants at a GWAS locus containing many SNPs in high LD. A The schematic cartoon plots show GWAS and MPRA SNPs and their corresponding significance at a single locus. LD structure confounds identification of the causal variant in the GWAS, but the MPRA tests regulatory effects of each SNP independently so it can identify a specific causal variant. B. Top, SNP association statistics at a genome-wide significant locus from an ASD GWAS [19]. The index SNP, rs60527016, reached genome-wide significance. SNPs are colored by binned LD (r²) relative to the MPRA-validated variant (rs7001340). The existence of SNPs that are in high LD with rs7001340 highlights the difficulties in defining which SNPs are functional or causal based on GWAS alone. Bottom, MPRA identified a causal variant within this locus (rs7001340) that shows strong allelic regulatory activity. Image adapted from [19]