Genetic Etiology in Pelvic Organ Prolapse: Role of Connective Tissue Homeostasis, Hormone Metabolism, and Oxidative Stress.

: Pelvic organ prolapse (POP) has become a common health problem among the aging population and affects an increasing number of elderly women worldwide. Studies within family and twin pairs provided strong evidence for the contribution of genetic factors to POP. Given the incomplete penetrance, polygenic traits, and small effect sizes of each variant in complex diseases, it is not always easy to evaluate the genetic susceptibility and molecular mechanisms involved in POP. : This review intends to comprehensively summarize the current studies on genetic variants associated with POP. : We performed a comprehensive review to summarize the genetic findings from genome-linkage studies, genome-wide association studies, candidate association studies, and gene expression analyses. : We summarized genetic variants associated with connective tissue homeostasis, hormone metabolism, and oxidative stress, which were potentially related to the pathophysiology of POP. We also reviewed the limited polygenic risk score (PRS) studies generated for each individual's genetic risk stratification and its integration into clinical risk factors for disease prediction. : This pooled analysis provides moderate epidemiological credibility for associations of these genetic variants with POP to bridge the gap between genetic research and clinical medicine towards understanding the genetic etiology of POP. It also highlights the potential of PRS as a risk prediction model.