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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 thermal structure of subduction zones exerts a major influence on deep-seated mechanical and chemical processes controlling arc magmatism, seismicity, and global element cycles. Accretionary complexes exposed inland may comprise tectonic blocks with contrasting pressure-temperature (P-T) histories, making it possible to investigate the dynamics and thermal evolution of former subduction interfaces. With this aim, we present new Lu-Hf geochronological results for mafic rocks of the Halilbagi Complex (Anatolia) that evolved along different thermal gradients. Samples include a lawsonite-epidote blueschist, a lawsonite-epidote eclogite, and an epidote eclogite (all with counter-clockwise P-T paths), a prograde lawsonite blueschist with a "hairpin"-type P-T path, and a garnet amphibolite from the overlying sub-ophiolitic metamorphic sole. Equilibrium phase diagrams suggest that the garnet amphibolite formed at similar to 0.6-0.7 GPa and 800-850 degrees C, whereas the prograde lawsonite blueschist records burial from 2.1 GPa and 420 degrees C to 2.6 GPa and 520 degrees C. Well-defined Lu-Hf isochrons were obtained for the epidote eclogite (92.38 +/- 0.22 Ma) and the lawsonite-epidote blueschist (90.19 +/- 0.54 Ma), suggesting rapid garnet growth. The lawsonite-epidote eclogite (87.30 +/- 0.39 Ma) and the prograde lawsonite blueschist (ca. 86 Ma) are younger, whereas the garnet amphibolite (104.5 +/- 3.5 Ma) is older. Our data reveal a consistent trend of progressively decreasing geothermal gradient from granulite-facies conditions at similar to 104 Ma to the epidote-eclogite facies around 92 Ma, and the lawsonite blueschist-facies between 90 Ma and 86 Ma. Three Lu-Hf garnet dates (between 92 Ma and 87 Ma) weighted toward the growth of post-peak rims (as indicated by Lu distribution in garnet) suggest that the HP/LT rocks were exhumed continuously and not episodically. We infer that HP/LT metamorphic rocks within the Halilbagi Complex were subjected to continuous return flow, with "warm" rocks being exhumed during the tectonic burial of "cold" ones. Our results, combined with regional geological constraints, allow us to speculate that subduction started at a transform fault near a mid-oceanic spreading centre. Following its formation, this ancient subduction interface evolved thermally over more than 15 Myr, most likely as a result of heat dissipation rather than crustal underplating. (C) 2018, China University of Geosciences (Beijing) and Peking University. Production and hosting by Elsevier B.V.
In this study, we detect high percentile rainfall events in the eastern central Andes, based on Tropical Rainfall Measuring Mission (TRMM) with a spatial resolution of 0.25 × 0.25°, a temporal resolution of 3 h, and for the duration from 2001 to 2018. We identify three areas with high mean accumulated rainfall and analyze their atmospheric behaviour and rainfall characteristics with specific focus on extreme events. Extreme events are defined by events above the 95th percentile of their daily mean accumulated rainfall. Austral summer (DJF) is the period of the year presenting the most frequent extreme events over these three regions. Daily statistics show that the spatial maxima, as well as their associated extreme events, are produced during the night. For the considered period, ERA-Interim reanalysis data, provided by the European Centre for Medium-Range Weather Forecasts (ECMWF) with 0.75° x0.75° spatial and 6-hourly temporal resolutions, were used for the analysis of the meso- and synoptic-scale atmospheric patterns. Night- and day-time differences indicate a nocturnal overload of northerly and northeasterly low-level humidity flows arriving from tropical South America. Under these conditions, cooling descending air from the mountains may find unstable air at the surface, giving place to the development of strong local convection. Another possible mechanism is presented here: a forced ascent of the low-level flow due to the mountains, disrupting the atmospheric stratification and generating vertical displacement of air trajectories. A Principal Component Analysis (PCA) in T-mode is applied to day- and night-time data during the maximum and extreme events. The results show strong correlation areas over each subregion under study during night-time, whereas during day-time no defined patterns are found. This confirms the observed nocturnal behavior of rainfall within these three hotspots.