About eight million people in Germany suffer from a chronic kidney disease, and 8000 of them require a kidney transplant. In order to develop effective new therapeutics, however, we first need a comprehensive understanding of the underlying processes of chronic kidney disease. In a project lasting three years, a team of scientists from more than 270 research departments worldwide has now analysed and evaluated the genomes of 1.05 million study participants. They found new loci as well as new risk genes associated with kidney disease. The researchers were particularly interested in the genes that influence the ability of the kidneys to purify the blood by filtering pollutants.
Around 14,000 data sets from Leipzig
In order to prove that certain genes are linked to kidney disease, the scientists carried out large data analyses under the leadership of the University Medical Center in Freiburg. They evaluated data sets from the international Chronic Kidney Disease Genetics (CKDGen) Consortium and the United States Million Veteran Program. The results were collected from around 100 studies worldwide. “The size of the data set made it possible to locate so many new and statistically significant genes and loci as well as genetic relationships to other traits such as body measurements and metabolic parameters,” explains Professor Markus Scholz, senior author and Professor of Genetic Statistics and Biomathematical Modelling at the Institute for Medical Informatics, Statistics and Epidemiology (IMISE). In addition to their high level of expertise in the field of genetic statistics, the Leipzig scientists also contributed data sets from the studies run by the Leipzig Research Centre for Civilization Diseases (LIFE) and a study of Sorbs. “From all three major LIFE cohorts – adults, the cardiac study and LIFE Child – we were able to provide data from approximately 14,000 people, making us one of the consortium’s ten largest partners worldwide. These high case numbers enable us to identify the often manifold genetic causes of diseases,” continued Professor Scholz.
Eleven genes particularly promising for new therapeutic approaches
As a result, the study has succeeded in identifying 166 new gene sites, or loci, for the first time. “We suspect that changes in these genes may promote kidney disease. Based on our study, it is now possible to better assess an individual’s genetic risk of developing kidney disease,” remarked Scholz. According to the researchers, risk variants in eleven of these genes are directly causal and could therefore have a role to play in areas such as the development of new drugs. The scientists also compared the gene activity of 46 tissue types throughout the body and were able to show that many relevant gene alterations lead to a change in gene activity in the tissue of the kidneys and the urogenital tract.
Our kidneys clean and filter our blood. Each day, they clean the six litres or so of blood in the human body approximately 300 times: important substances such as proteins and minerals remain in the blood, while metabolic waste is filtered out by the organ and excreted in the urine. Of the approximately 180 litres filtered out of the blood every day, only two to three litres enter the bladder in concentrated form, with the rest remaining in the body. Kidney function in adults steadily decreases with age; if it is permanently restricted, a variety of symptoms can occur. These include swelling of the legs or face, fatigue, nausea, weight loss, muscle cramps and even end-stage renal disease. Chronic kidney disease has been one of the most rapidly increasing causes of death in the last ten years.
contact for scientific information:
Prof. Dr. Markus Scholz
Institut für Medizinische Informatik, Statistik und Epidemiologie (IMISE)
Telefon: +49 341 97-16100
“A catalog of genetic loci associated with kidney function from analyses of a million individuals”, DOI: 10.1038/s41588-019-0407-x