New sex-specific genetic variants for chronic kidney disease identified

In collaboration with an international consortium, scientists from the University of Leipzig have identified new genes that may play a role in chronic kidney disease. They analyzed data from more than 900,000 people and found effects that, in some cases, differed between men and women.

These new findings could help scientists better understand sex-specific differences in the risk and progression of chronic kidney disease and provide a starting point for appropriate treatments. The results were recently published in Natural communications.

Approximately 10% of the world’s population currently suffers from chronic kidney disease (CKD). This puts people at increased risk of kidney failure, cardiovascular disease and hospitalization, and places a heavy burden on the healthcare system. Due to demographic changes related to the aging population, it is predicted that CKD could become one of the top five causes of death worldwide by 2040.

In a large-scale study, scientists from the University of Leipzig, together with other international study groups, investigated the genetic associations between variants of the X chromosome and seven selected parameters of kidney function in men and women. The study was based on blood samples and genetic information from a total of more than 900,000 people, 80% of whom were of European descent.

“We identified a total of 23 associations: 16 are linked to the estimated glomerular filtration rate of the kidney and seven to uric acid,” explains study leader Professor Markus Scholz from the Institute for Medical Informatics. , Statistics and Epidemiology (IMISE) at the University of Leipzig. Along with uric acid, glomerular filtration rate is a key measure of kidney health. It shows how much blood the glomeruli (small vessels in kidney tissue) can filter per unit of time.

The researchers found different effects in men and women at six positions in the genome. The scientists were able to assign functionally plausible candidate genes to the newly discovered genetic effects.

“Sex-specific differences could be explained by hormonal regulation of associated genes,” reports Katrin Horn, analyst of the IMISE study.

“This discovery helps us to better understand the possible mechanisms of development and progression of the disease,” explains Professor Markus Scholz. “For example, we already know that the disease is more common in women, but progresses more quickly in men. We now have appropriate mechanisms to investigate these phenomena further.”

In their analysis of X chromosome variants, the Leipzig scientists looked at mutations at around 270,000 positions on the chromosome and correlated them with clinical kidney parameters. They also used tissue data to test whether and how genetic information was actually used. A targeted search for gender differences was carried out.

“We deliberately chose to analyze the more complex X chromosome, which has not yet been sufficiently studied in terms of genetic associations, although it shows great promise regarding sex differences in disease.” , explains Professor Scholz, researcher in bioinformatics. “The reason is that women have two of these chromosomes, but the genetic information is only partially used and it is not understood exactly how and to what extent this happens.”

The method that Professor Scholz and his team developed for this study to analyze the X chromosome in detail and identify sex-specific differences may also be used by other research teams in the future to help gender-sensitive medicine for other diseases.

The study was part of the international CKDGen consortium for research into the genetics of kidney diseases, led by Professor Anna Köttgen from the University of Freiburg, with the University of Leipzig as a key partner. It included data from the Leipzig LIFE Heart, LIFE Adult, LIFE Child and Sorb Study, in a total of around 14,000 data records. Most of the analysis and interpretation of the data was carried out by Professor Scholz’s research group.