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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.
In this work we present spectra of all gamma-ray burst (GRB) afterglows that have been promptly observed with the X-shooter spectrograph until 31/03/2017. In total, we have obtained spectroscopic observations of 103 individual GRBs observed within 48 hours of the GRB trigger. Redshifts have been measured for 97 per cent of these, covering a redshift range from 0.059 to 7.84. Based on a set of observational selection criteria that minimise biases with regards to intrinsic properties of the GRBs, the follow-up effort has been focused on producing a homogeneously selected sample of 93 afterglow spectra for GRBs discovered by the Swift satellite. We here provide a public release of all the reduced spectra, including continuum estimates and telluric absorption corrections. For completeness, we also provide reductions for the 18 late-time observations of the underlying host galaxies. We provide an assessment of the degree of completeness with respect to the parent GRB population, in terms of the X-ray properties of the bursts in the sample and find that the sample presented here is representative of the full Swift sample. We have constrained the fraction of dark bursts to be <28 per cent and confirm previous results that higher optical darkness is correlated with increased X-ray absorption. For the 42 bursts for which it is possible, we have provided a measurement of the neutral hydrogen column density, increasing the total number of published HI column density measurements by similar to 33 per cent. This dataset provides a unique resource to study the ISM across cosmic time, from the local progenitor surroundings to the intervening Universe.
We present a survey for metal absorption systems traced by neutral oxygen over 3.2 < z < 6.5. Our survey uses Keck/ESI and VLT/X-Shooter spectra of 199 QSOs with redshifts up to 6.6. In total, we detect 74 OI absorbers, of which 57 are separated from the background QSO by more than 5000 km s(-1). We use a maximum likelihood approach to fit the distribution of OI lambda 1302 equivalent widths in bins of redshift and from this determine the evolution in number density of absorbers with W-1302 > 0.05 angstrom, of which there are 49 nonproximate systems in our sample. We find that the number density does not monotonically increase with decreasing redshift, as would naively be expected from the buildup of metal-enriched circumgalactic gas with time. The number density over 4.9 < z < 5.7 is a factor of 1.7-4.1 lower (68% confidence) than that over 5.7 < z < 6.5, with a lower value at z < 5.7 favored with 99% confidence. This decrease suggests that the fraction of metals in a low-ionization phase is larger at z similar to 6 than at lower redshifts. Absorption from highly ionized metals traced by CIV is also weaker in higher-redshift OI systems, supporting this picture. The evolution of OI absorbers implies that metal-enriched circumgalactic gas at z similar to 6 is undergoing an ionization transition driven by a strengthening ultraviolet background. This in turn suggests that the reionization of the diffuse intergalactic medium may still be ongoing at or only recently ended by this epoch.