New genetic variants associated with pelvic organ prolapse have been found

A study led by researchers from the Institute of Genomics, University of Tartu identified 22 new genetic variants associated with pelvic organ prolapse and evaluates polygenic risk scores as a potential tool to enhance individual risk prediction. The study was published in Nature Communications.

A feeling of pressure or as if something is falling out of your pelvic area, urinary problems, painful intercourse – these are the symptoms of pelvic prolapse, a gynecological condition affecting around 40% of women after menopause. It is characterized by the descent of the pelvic organs (bladder, rectum and/or uterus) into the vaginal cavity, and it is the main cause for surgical removal of the uterus.

The onset of this condition is due to the complex interaction of both biological and environmental factors, but it is also heritable. However, the identification of genetic variants associated with this condition, and how these might affect certain biological processes, remains understudied. The largest study on the genetics of pelvic organ prolapse led by a group of scientists from the Institute of Genomics, University of Tartu has identified 22 new genetic variants related to this gynecological condition, which represent a solid step to understanding which biological factors contribute to it and tests how genetic risk helps predict its development.

“Methods that enable a massive analysis of genetic information and large biobanks have truly revolutionised the studies into the genetic and molecular mechanisms of gynecological conditions like pelvic organ prolapse,” said dr Triin Laisk, Associate Professor of Genomics and Reproductive Genetics and senior author of the study. In this study, the researchers studied more than 15 million genetic variations in the DNA sequence of over 500,000 women, of whom more than 28,000 had pelvic organ prolapse.

"This is the most complete genetic study in history for pelvic prolapse, and its results open a way to better understand how this condition manifests," says Natàlia Pujol Gualdo, PhD student at the Institute of Genomics, University of Tartu, and first author of the study.

The associated variants were found in genes involved in specific biological pathways related to connective tissue, urogenital development and cardiometabolic health. The study also found a genetic link with other pathologies, especially those related to connective tissue abnormalities, such as inguinal hernia and gastro-esophageal reflux, which may help to explain why these conditions often occur together.

The scientists used the data from female Estonian Biobank participants and also tested how well a summarised genetic risk could predict the development of prolapse later in life, alone and taking also into account other risk factors for pelvic organ prolapse such as body mass index, smoking status, number of children, constipation, and asthma.

"Although the total predictive ability obtained is not accurate enough to implement in the clinical practice alone, we showed genetic risk substantially helps to improve predictive power on top of the other known risk factors, which could tailor individualized preventive strategies even decades before symptoms of prolapse appear," said Laisk.

"All these findings open up new avenues of research regarding the understanding of biological mechanisms underlying pelvic organ prolapse, generation of possible new therapeutic targets, as well as for the study of risk stratification and enhanced predictive ability using genetic risk," explains Pujol Gualdo.

Other researchers and clinicians from the University of Oulu have also participated in this research. Thanks to all biobank participants in the project the authors were able to analyze genetic data of over 500 000 women from the Estonian Biobank, FinnGen study, UK Biobank and Icelandic cohorts.