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An international team of researchers led by the Freiburg University Medical Center has discovered many new genes that influence the predisposition to gout and other metabolic diseases / Study of over 457,000 volunteers

Gout is the most common form of inflammatory arthritis, in which an increased concentration of uric acid in the blood can lead to the painful deposition of uric acid crystals. Researchers at the University Medical Center Freiburg, together with international colleagues from 195 scientific institutions within the CKDGen Consortium, have now been able to show how strong the influence of hereditary factors is on the risk of gout and why the uric acid concentration is also associated with other metabolic disorders. Using data from more than 457,000 study participants worldwide, they identified 183 gene loci that have an influence on uric acid levels. Such a connection has now been proven for the first time for 147 of these gene loci. The results of the study were published in the journal Nature Genetics on October 2, 2019.

Proving that and how the occurrence of certain gene variants is associated with a disease is a highly complex scientific task. "Thanks to the enormous size of our study, we were able to identify numerous genetic changes that influence uric acid levels in the blood and the risk of gout," says study leader Prof. Dr. Anna Köttgen, Director of the Institute of Genetic Epidemiology at the Freiburg University Medical Center. "The incidence of gout is 100 times higher in the group of people with a strong hereditary predisposition than in people with a very low hereditary predisposition."

Data analyses and laboratory studies provide evidence of other metabolic diseases

The scientists also identified gene variants that have an impact on the regulatory mechanisms of the uric acid balance and could explain the long-observed connection with other metabolic diseases such as elevated blood lipid levels. "We initially identified these novel correlations by linking various large genetic and clinical data sets, primarily on the computer. I am therefore particularly pleased that we were subsequently able to confirm our assumptions for selected examples in the laboratory," says co-first author Dr. Matthias Wuttke, physician and scientist at the Institute of Genetic Epidemiology at the Freiburg University Medical Center.

"Thanks to our analyses, we now have a veritable atlas of relevant genetic changes, genes, tissues and mechanisms for urea metabolism. We are confident that our results will improve the development of therapies for gout in the long term as starting points for follow-up studies and would like to thank all study participants for their voluntary participation," says co-first author Dr. Yong Li from the Institute of Genetic Epidemiology.

Caption: Gout, blood lipid levels, diabetes, obesity: The predisposition to elevated uric acid concentrations in the blood is linked to a wide variety of complaints, as the current study shows.

Image source: University Medical Center Freiburg

Original title of the study: Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels

DOI: 10.1038/s41588-019-0504-x

Link to the study: https: //www.nature.com/articles/s41588-019-0504-x

Contact: 
Prof. Dr. med. Anna Köttgen 
Director 
Institute of Genetic Epidemiology 
University Medical Center Freiburg 
Phone: 0761 270-78050 
anna.koettgen@uniklinik-freiburg.de