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posted on 2021-04-19, 17:32 authored by Anqi Zhu, Nana Matoba, Emma P. Wilson, Amanda L. Tapia, Yun Li, Joseph G. Ibrahim, Jason L. Stein, Michael I. Love

MRLocus estimates the gene-to-trait effect (solid blue line) as the slope from paired eQTL and GWAS effect sizes from independent signal clusters (black points with standard error bars), here on simulated coefficients. The dispersion of allelic effects around the main gene-to-trait effect (light blue band) is also estimated. An 80% credible interval on the slope is indicated with dashed blue lines sloping above and below the solid blue line. Panels represent loci demonstrating (A) mediation with low dispersion, (B) mediation with high dispersion, and (C) colocalization of eQTL and GWAS signals but no evidence of mediation (slope credible interval overlaps 0). Investigators may wish to prioritize loci for experimental follow-up in which a typical “dosage” pattern is observed, such that alleles contributing small amounts to expression of a gene contribute small amounts to GWAS trait, and similarly for large effect alleles.

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