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A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry 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.
We compare dictator and impunity games. In impunity games, responders can reject offers but to no payoff consequence to proposers. Because proposers act under impunity, we should expect the same behavior across games, but experimentally observed behavior varies. Responders indeed exercise the rejection option. This threat psychologically influences proposers. Some proposers avoid rejection by offering nothing. Others raise offers, but only when they receive feedback from responders. Responders lose this influence in the absence of feedback. (C) 2016 Elsevier B.V. All rights reserved.