Quantifying the impact of genetically regulated expression on complex traits and diseases

Abstract

About 90% of risk variants identified from genome-wide association studies (GWAS) are located in non-coding regions, highlighting the regulatory role of genetic variants. We propose a unified statistical framework, IGREX, for quantifying the impact of genetically regulated expression (GREX). This is achieved by estimating proportion of phenotypic variations that can be explained by the GREX component. IGREX only requires summary-level GWAS data and a gene expression reference panel as input. In real data analysis, using 48 tissues from the GTEx project as the reference panel, we applied IGREX to a wide spectrum of phenotypes in GWAS, and observed a significant proportion of phenotypic variations could be attributed to the GREX component. In particular, the results given by IGREX revealed tissue-across and tissue-specific patterns of the GREX effects. We also observed strong association between GREX effect and immune-related proteins, further supporting the relevance between GREX and the immune processes.