AbstractThe driver tissues or cell types in which susceptibility genes initiate diseases remain elusive. We develop a unified framework to detect the causal tissues of complex diseases or traits according to selective expression of disease-associated genes in genome-wide association studies (GWASs). This framework consists of three components which run iteratively to produce a converged prioritization list of driver tissues. Additionally, this framework also outputs a list of prioritized genes as a byproduct. We apply the framework to six representative complex diseases or traits with GWAS summary statistics, which leads to the estimation of the lung as an associated tissue of rheumatoid arthritis.