Fig. 4: Identifying driver regulatory mechanisms for SCZ risk genes using Mendelian Randomization (MR).
From: Impact of common variants on brain gene expression from RNA to protein to schizophrenia risk
A Summaries of MR test results. Left panel: Two-sample MR replication of S-PrediXcan SCZ risk gene discoveries. Each circle represents a S-PrediXcan discovery. A solid-colored circle indicates successful replication in a MR test. Right panel: One-sample MR test results for causality between omics types. Shown are MR effect size +/− the corresponding standard errors estimated using 185 samples. Red data points indicate significant test results. Ribo: ribosome occupancy. B, C Example SCZ risk genes driven by either transcriptional regulation of protein expression (B) or transcript-specific effects (C). Manhattan plots on the left show nominal p-values for all variants in the QTL mapping window for each omics and SCZ GWAS, with the red vertical line indicating the top signal colocalization SNP between QTL and GWAS. Boxplots on the right summarize the normalized gene expression level stratified by QTL SNP genotype across 185 samples. Boxes represent the interquartile range (IQR), spanning from the 25th percentile (lower bound) to the 75th percentile (upper bound), with the median (center line) shown inside the box. Whiskers extend to 1.5 × IQR. The effect size estimates from the corresponding one-sample MR causality tests between each pair of omics and two-sample MR tests replicating the risk gene discoveries are shown in the plot beneath. MR effect +/− the corresponding standard errors were estimated using 185 samples.
