An international researcher group has discovered the identity of genes that predispose people to chronic kidney disease.
The discovery is a major advance in understanding of the significantly under-diagnosed disorder which, if left undetected, can lead to failing kidneys that need dialysis or kidney transplantation.
The discovery of 35 kidney genes published in Nature Communications is an important step forward to the future development of new diagnostic tests and treatments for the disease that affects around one in ten adults.
Using 280 kidney transcriptomes and 9958 gene expression profiles from 44 non-renal tissues authors uncover gene expression partners (eGenes) for 88.9% of CKD-dt GWAS loci. Through epigenomic chromatin segmentation analysis and variant effect prediction we annotate functional consequences to 74% of these loci.
The colocalisation analysis and Mendelian randomisation in >130,000 subjects demonstrate causal effects of three eGenes (NAT8B, CASP9 and MUC1) on estimated glomerular filtration rate.
"Our limited knowledge of its exact genetic mechanisms partly explains why progress in the development of new diagnostic tests and treatments of chronic kidney disease has been so slow. We hope that some of the kidney genes we discovered may become attractive targets for the development of future diagnostics and treatment for patients with chronic kidney disease."
AUthors identify a common alternative splice variant in MUC1 (a gene responsible for rare Mendelian form of kidney disease) and observe increased renal expression of a specific MUC1 mRNA isoform as a plausible molecular mechanism of the GWAS association signal.
Co-author said: "One of the genes - mucin-1- is especially interesting."It makes a sticky protein called mucin that coats urinary tubes inside the kidney. Mutations of this gene have already been found in rare families with inherited kidney failure."
https://www.manchester.ac.uk/discover/news/revealed-35-kidney-genes-linked-to-chronic-kidney-disease-risk/
https://www.nature.com/articles/s41467-018-07260-4\
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fmolecular-insights-into&filter=22
35 kidney genes linked to chronic kidney disease risk
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