Polymorphism in maternal HLA-DRB5 is associated with the risk of preeclampsia in Chinese population

Abstract Background: Preeclampsia is an important clinical syndrome occurring during pregnancy. It shows genetic disposition, and the genetic risk has large ethnic heterogeneity. The study was designed to investigate the genetic risk of preeclampsia in Chinese pregnancies, and to apply it in early screening of the disease. Methods: We performed a genome-wide association study to screen candidate risk loci associated with preeclampsia in Chinese people, and validated them with an independent cohort of enlarged size. We also trained prediction models using the genotypes of newly identified risk loci to screen the pregnancies with high preeclampsia risk. Results: A segment in chromosome 6 covering HLA-DQB1 , HLA-DRB5 and other immune-related genes shows the most significant association, and three loci in HLA-DRB5 were confirmed with an enlarged validation cohort. One of the validated loci, rs147440497, forms an amino acid change by the nucleotide polymorphism, which further causes a conformational change in the antigen-binding domain of HLA-DRB5 protein. With the genotypes of risk genetic loci and other demographic features, a machine-learning model was trained, which can predict Chinese preeclampsia pregnancies accurately, with a cross-validated recalling rate of 0.63 at a false positive rate of 8%. Conclusion: We identified a novel gene from maternal genome, HLA-DRB5 , the polymorphism in which is associated with preeclampsia. The genotypes of risk SNP loci can also be used for prediction of preeclampsia risk in Chinese population accurately.