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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 magnetosphere-ionosphere-thermosphere (MIT) dynamic system significantly depends on the highly variable solar wind conditions, in particular, on changes of the strength and orientation of the interplanetary magnetic field (IMF). The solar wind and IMF interactions with the magnetosphere drive the MIT system via the magnetospheric field-aligned currents (FACs). The global modeling helps us to understand the physical background of this complex system. With the present study, we test the recently developed high-resolution empirical model of field-aligned currents MFACE (a high-resolution Model of Field-Aligned Currents through Empirical orthogonal functions analysis). These FAC distributions were used as input of the time-dependent, fully self-consistent global Upper Atmosphere Model (UAM) for different seasons and various solar wind and IMF conditions. The modeling results for neutral mass density and thermospheric wind are directly compared with the CHAMP satellite measurements. In addition, we perform comparisons with the global empirical models: the thermospheric wind model (HWM07) and the atmosphere density model (Naval Research Laboratory Mass Spectrometer and Incoherent Scatter Extended 2000). The theoretical model shows a good agreement with the satellite observations and an improved behavior compared with the empirical models at high latitudes. Using the MFACE model as input parameter of the UAM model, we obtain a realistic distribution of the upper atmosphere parameters for the Northern and Southern Hemispheres during stable IMF orientation as well as during dynamic situations. This variant of the UAM can therefore be used for modeling the MIT system and space weather predictions.
Water stable isotope signatures can provide valuable insights into the catchment internal runoff processes. However, the ability of the water isotope data to constrain the internal apportionments of runoff components in hydrological models for glacierized basins is not well understood. This study developed an approach to simultaneously model the water stable isotopic compositions and runoff processes in a glacierized basin in Central Asia. The fractionation and mixing processes of water stable isotopes in and from the various water sources were integrated into a glacio-hydrological model. The model parameters were calibrated on discharge, snow cover and glacier mass balance data, and additionally isotopic composition of streamflow. We investigated the value of water isotopic compositions for the calibration of model parameters, in comparison to calibration methods without using such measurements. Results indicate that: (1) The proposed isotope-hydrological integrated modeling approach was able to reproduce the isotopic composition of streamflow, and improved the model performance in the evaluation period; (2) Involving water isotopic composition for model calibration reduced the model parameter uncertainty, and helped to reduce the uncertainty in the quantification of runoff components; (3) The isotope-hydrological integrated modeling approach quantified the contributions of runoff components comparably to a three-component tracer-based end-member mixing analysis method for summer peak flows, and required less water tracer data. Our findings demonstrate the value of water isotopic compositions to improve the quantification of runoff components using hydrological models in glacierized basins.
To better understand how climate change might influence global canola production, scientists from six countries have completed the first inter-comparison of eight crop models for simulating growth and seed yield of canola, based on experimental data from six sites across five countries. A sensitivity analysis was conducted with a combination of five levels of atmospheric CO2 concentrations, seven temperature changes, five precipitation changes, together with five nitrogen application rates. Our results were in several aspects different from those of previous model inter-comparison studies for wheat, maize, rice, and potato crops. A partial model calibration only on phenology led to very poor simulation of aboveground biomass and seed yield of canola, even from the ensemble median or mean. A full calibration with additional data of leaf area index, biomass, and yield from one treatment at each site reduced simulation error of seed yield from 43.8 to 18.0%, but the uncertainty in simulation results remained large. Such calibration (with data from one treatment) was not able to constrain model parameters to reduce simulation uncertainty across the wide range of environments. Using a multi-model ensemble mean or median reduced the uncertainty of yield simulations, but the simulation error remained much larger than observation errors, indicating no guarantee that the ensemble mean/median would predict the correct responses. Using multi-model ensemble median, canola yield was projected to decline with rising temperature (2.5-5.7% per degrees C), but to increase with increasing CO2 concentration (4.6-8.3% per 100-ppm), rainfall (2.1-6.1% per 10% increase), and nitrogen rates (1.3-6.0% per 10% increase) depending on locations. Due to the large uncertainty, these results need to be treated with caution. We further discuss the need to collect new data to improve modelling of several key physiological processes of canola for increased confidence in future climate impact assessments.
Projections of changes in Antarctic Ice Sheet (AIS) surface mass balance indicate a negative contribution to sea level because of the expected increase in precipitation due to the higher moisture holding capacity of warmer air(1). Observations over the past decades, however, are unable to constrain the relation between temperature and accumulation changes because both are dominated by strong natural variability(2-5). Here we derive a consistent continental-scale increase in accumulation of approximately 5 +/- 1% K-1, through the assessment of ice-core data (spanning the large temperature change during the last deglaciation, 21,000 to 10,000 years ago), in combination with palaeo-simulations, future projections by 35 general circulation models (GCMs), and one high-resolution future simulation. The ice-core data and modelling results for the last deglaciation agree, showing uniform local sensitivities of similar to 6% K-1. The palaeo-simulation allows for a continental-scale aggregation of accumulation changes reaching 4.3% K-1. Despite the different timescales, these sensitivities agree with the multi-model mean of 6.1 +/- 2.6% K-1 (GCMprojections) and the continental-scale sensitivity of 4.9% K-1 (high-resolution future simulation). Because some of the mass gain of the AIS is offset by dynamical losses induced by accumulation(6,7), we provide a response function allowing projections of sea-level fall in terms of continental-scale accumulation changes that compete with surface melting and dynamical losses induced by other mechanisms(6,8,9).