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Olle Melander

Principal investigator

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A catalog of genetic loci associated with kidney function from analyses of a million individuals

Author

  • Matthias Wuttke
  • Peter Almgren
  • Cecilia M Lindgren
  • Olle Melander
  • Marju Orho-Melander
  • Markus Perola
  • Christina-Alexandra Schulz
  • Hauke Thomsen
  • Lars Wallentin
  • Cristian Pattaro

Summary, in English

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.

Department/s

  • Cardiovascular Research - Hypertension
  • Diabetes - Cardiovascular Disease
  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health
  • Department of Clinical Sciences, Malmö

Publishing year

2019-05-31

Language

English

Pages

957-972

Publication/Series

Nature Genetics

Volume

51

Issue

6

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics

Status

Published

Research group

  • Cardiovascular Research - Hypertension
  • Diabetes - Cardiovascular Disease
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1546-1718