Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals
Year: 2021
Type: review
Study design: Observational Study
Abstract: Genes underneath signals from genome-wide association studies (GWAS) for kidney function are promising targets for functional studies, but prioritizing variants and genes is challenging. By GWAS meta-analysis for creatinine-based estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics Consortium and UK Biobank (n = 1,201,909), we expand the number of eGFRcrea loci (424 loci, 201 novel; 9.8% eGFRcrea variance explained by 634 independent signal variants). Our increased sample size in fine-mapping (n = 1,004,040, European) more than doubles the number of signals with resolved fine-mapping (99% credible sets down to 1 variant for 44 signals, ≤5 variants for 138 signals). Cystatin-based eGFR and/or blood urea nitrogen association support 348 loci (n = 460,826 and 852,678, respectively). Our customizable tool for Gene PrioritiSation reveals 23 compelling genes including mechanistic insights and enables navigation through genes and variants likely relevant for kidney function in human to help select targets for experimental follow-up.
Source: Nature Communications
Authors: Kira J. Stanzick, Yong Li, Pascal Schlosser, Mathias Gorski, Matthias Wuttke, Laurent F. Thomas, Humaira Rasheed, Bryce X. Rowan, Sarah E. Graham, Brett R. Vanderweff, Snehal B. Patil, VA Million Veteran Program, Cassiane Robinson-Cohen, John M. Gaziano, Christopher J. O’Donnell, Cristen J. Willer, Stein Hallan, Bjørn Olav Åsvold, Andre Gessner, Adriana M. Hung, Cristian Pattaro, Anna Köttgen, Klaus J. Stark, Iris M. Heid, Thomas W. Winkler
Institutions: University of Regensburg, University of Freiburg, University Medical Center Freiburg, Norwegian University of Science and Technology, University of Bristol, MRC Integrative Epidemiology Unit, Vanderbilt University, VA Tennessee Valley Healthcare System, Vanderbilt University Medical Center, University of Michigan, Michigan Medicine, VA Boston Healthcare System, Harvard University, St Olav's University Hospital, University Hospital Regensburg, Eurac Research, Institute for Biomedicine, Johns Hopkins University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,721
Funders: Foundation for the National Institutes of Health, U.S. Department of Veterans Affairs, Office of Research and Development, Norges Teknisk-Naturvitenskapelige Universitet, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Albert-Ludwigs-Universität Freiburg, Helse Midt-Norge, Universität Regensburg, National Institutes of Health, Fakultet for medisin og helsevitenskap, Norges Teknisk-Naturvitenskapelige Universitet, Medical Research Council, Faculty of Medicine and Health, University of Sydney, Norwegian Institute of Public Health, Medizinische Fakultät der Albert-Ludwigs-Universität Freiburg
Awards: Identifizierung und Charakterisierung der genetischen Basis von altersbedingter Makuladegeneration unter spezieller Berücksichtigung von geschlechtsspezifischen Effekten, G2408266837, G2605962356, G2742816485, G3055204393, G3580366574, Identifizierung und Charakterisierung der genetischen Basis von altersbedingter Makuladegeneration unter spezieller Berücksichtigung von geschlechtsspezifischen und anderen nicht-genetischen Effekten (2. Förderphase), SFB 1350: Tubulussystem und Interstitium der Niere: (Patho)Physiologie und Crosstalk, SFB 1453: Nephrogenetik (NephGen), G4397854981, G4629635766, G512330343, G561423854, G5850737185, G7099572599, G844398614
OpenAlex ID: W3182222456