The impact of rare variation on gene expression across tissues

Rare genetic variants are abundant in humans yet their functional effects are often unknown and challenging to predict. The Genotype-Tissue Expression (GTEx) project provides a unique opportunity to identify the functional impact of rare variants through combined analyses of whole genomes and multi-tissue RNA-sequencing data. Here, we identify gene expression outliers, or individuals with extreme expression levels, across 44 human tissues, and characterize the contribution of rare variation to these large changes in expression. We find 58% of underexpression and 28% of overexpression outliers have underlying rare variants compared with 9% of non-outliers. Large expression effects are enriche