We reasoned that if complete knock out of monogenic disease genes cause severe forms of the disease, more moderate alterations of gene expression levels (as affected by regulatory variation in the population) could cause more moderate forms of the disease. Thus moderate alterations in expression levels of monogenic disease genes (such as those driven by eQTLs) may have an effect on related complex traits, and this effect could be captured by S-PrediXcan association statistics. To test this hypothesis, we obtained genes listed in the ClinVar database30 for obesity, rheumatoid arthritis, diabetes, Alzheimer’s, Crohn’s disease, ulcerative colitis, age-related macular degeneration, schizophrenia, and autism. Figure 7 displays the QQ plot for all associations and compares to those in ClinVar database. As postulated, we found enrichment of significant S-PrediXcan associations for ClinVar genes for all tested phenotypes except for autism and schizophrenia. The lack of significance for autism is probably due to insufficient power: the distribution of p-values is close to the null distribution. In contrast, for schizophrenia, many genes were found to be significant in the S-PrediXcan analysis. There are several reasons
