Background: Intraocular pressure (IOP) is a major modifiable risk factor for glaucoma. However, the mechanisms underlying the controlling of IOP remain to be elucidated. Objective: To prioritize genes that are pleiotropically associated with IOP. Methods: We adopted a two-sample Mendelian randomization method, named summary-based Mendelian randomization (SMR), to examine the pleiotropic effect of gene expression on IOP. The SMR analyses were based on summarized data from a genome-wide association study (GWAS) on IOP. We conducted separate SMR analyses using Genotype-Tissue Expression (GTEx) and Consortium for the Architecture of Gene Expression (CAGE) expression quantitative trait loci (eQTL) data. Additionally, we performed a transcriptome-wide association study (TWAS) to identify genes whose cis-regulated expression levels were associated with IOP. Results: We identified 19 and 25 genes showing pleiotropic association with IOP using the GTEx and CAGE eQTL data, respectively.RP11-259G18.3(PSMR= 2.66 × 10−6),KANSL1-AS1(PSMR= 2.78 × 10−6), andRP11-259G18.2(PSMR= 2.91 × 10−6) were the top three genes using the GTEx eQTL data.LRRC37A4(PSMR= 1.19 × 10−5),MGC57346(PSMR= 1.19 × 10−5), andRNF167(PSMR= 1.53 × 10−5) were the top three genes using the CAGE eQTL data. Most of the identified genes were found in or near the 17q21.31 genomic region. Additionally, our TWAS analysis identified 18 significant genes whose expression was associated with IOP. Of these, 12 and 4 were also identified by the SMR analysis using the GTEx and CAGE eQTL data, respectively. Conclusions: Our findings suggest that the 17q21.31 genomic region may play a critical role in the regulation of IOP.