In this study, we used tissue-specific TWAS to explore the association of genetically predicted gene expression with cirrhosis in European ancestry and identified 10 genes in four tissues as potential cirrhosis-related genes, including two in the liver (SKIV2L and JPH4), three in the pancreas (UQCC2, RP11-91I8.3, and MAU2), two in the spleen (ERAP1 and PUS3), and three in thyroid tissue (ZNF677, ARHGAP40, and SHANK3). Here, SHANK3 is linked to Cirrhosis.