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Mining the genome for insights into kidney function and development

An international group of researchers, examining data from more than 230,000 people, have discovered 24 new areas of the genome (the entire set of genetic information) that are associated with kidney function or development, and have confirmed 29 other genomic areas that were previously identified. Estimates suggest that more than 20 million adults in the United States have chronic kidney disease (CKD), of varying levels of seriousness. To identify genes associated with CKD, a team of scientists scanned the genomes of more than 130,000 people of European ancestry for genetic variants associated with estimated glomerular filtration rate (eGFR), a measurement of how well their kidneys are filtering wastes and extra fluid from the blood. The researchers identified 24 new regions of the genome that were associated with kidney function and confirmed the findings by further analysis in more than 42,000 additional people of European ancestry. Their analysis also confirmed 29 genomic regions already known to be associated with eGFR. Many of these genomic regions were associated with eGFR in people with type 2 diabetes or high blood pressure—populations at particularly high risk for CKD. The scientists also examined the genomes of over 16,000 people of African ancestry and more than 42,000 Asians. Several of the newly identified regions were associated with kidney function in other ethnic groups, suggesting that these results likely extend beyond people of European ancestry. Computational analyses determined that genes found to be in these genomic regions were mostly turned on in cells within the kidney or urinary tract, and were involved in processes related to kidney development and function. The specific genomic variations associated with eGFR often resided in portions of the genes that determine when, where, and to what extent the genes are turned on. Additional studies will be necessary to understand the precise role of each genomic region in kidney development and physiology, but these findings have generated numerous potential targets for therapeutic strategies to improve kidney health, including in people with type 2 diabetes or high blood pressure.

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