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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.
The Atlantic meridional overturning circulation (AMOC)—a system of ocean currents in the North Atlantic—has a major impact on climate, yet its evolution during the industrial era is poorly known owing to a lack of direct current measurements. Here we provide evidence for a weakening of the AMOC by about 3 ± 1 sverdrups (around 15 per cent) since the mid-twentieth century. This weakening is revealed by a characteristic spatial and seasonal sea-surface temperature ‘fingerprint’—consisting of a pattern of cooling in the subpolar Atlantic Ocean and warming in the Gulf Stream region—and is calibrated through an ensemble of model simulations from the CMIP5 project. We find this fingerprint both in a high-resolution climate model in response to increasing atmospheric carbon dioxide concentrations, and in the temperature trends observed since the late nineteenth century. The pattern can be explained by a slowdown in the AMOC and reduced northward heat transport, as well as an associated northward shift of the Gulf Stream. Comparisons with recent direct measurements from the RAPID project and several other studies provide a consistent depiction of record-low AMOC values in recent years.