Objective Venous thromboembolism (VTE) is a common health problem. This study aimed to identify genetic variants associated with pregnancies with VTE. Design A case-control experimental study. Setting Ten hospitals in Shanghai. Sample Blood samples from 25 pregnant patients with VTE and 17 pregnant controls without VTE. Methods All samples were sequenced by whole exome sequencing (WES). Functional and enrichment analyses and PPI network were performed using DAVID and STRING database. Primary outcome P-value and OR were obtained by Pearson’s chi-squared test and logistic regression. Results 5810 significant variants annotated in 3417 genes, were associated with pregnancies with VTE (P < 0.05). Fifty-six variants annotated in 46 genes (P < 0.001) were identified. Logistic analysis revealed that rs7099478 in GRK5, rs8041208 in WDR72, rs17215792, rs13035688, rs6725221 and rs3214417 in KLF7 were associated with an increased risk of developing VTE (P < 0.05, OR > 1). In addition, Pathway and PPI analyses revealed that CDC7 and MCM6 involved with DNA replication were associated with VTE in pregnancies. Conclusions Several variants in KLF7, GRK5, and WDR72 may be genetic risk factors for VTE in pregnancies. CDC7 and MCM6 may be related to the pathogenic process of VTE in pregnancies. Notably, the KLF7 gene with 4 genetic variants was found to be associated with lipid metabolism and cardiovascular diseases. Funding The National Natural Science Foundation of China (No.81472990) and Clinical Research Project of Shanghai Municipal Commission of Health and Family Planning (No.201840095) Keywords Pregnant, Venous thromboembolism, whole exome sequencing, KLF7