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.
To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
An annihilation signal of dark matter is searched for from the central region of the Milky Way. Data acquired in dedicated on-off observations of the Galactic center region with H.E.S.S. are analyzed for this purpose. No significant signal is found in a total of similar to 9 h of on-off observations. Upper limits on the velocity averaged cross section, <sigma upsilon >, for the annihilation of dark matter particles with masses in the range of similar to 300 GeV to similar to 10 TeV are derived. In contrast to previous constraints derived from observations of the Galactic center region, the constraints that are derived here apply also under the assumption of a central core of constant dark matter density around the center of the Galaxy. Values of <sigma upsilon > that are larger than 3 x 10(-24) cm(3)/s are excluded for dark matter particles with masses between similar to 1 and similar to 4 TeV at 95% C.L. if the radius of the central dark matter density core does not exceed 500 pc. This is the strongest constraint that is derived on <sigma upsilon > for annihilating TeV mass dark matter without the assumption of a centrally cusped dark matter density distribution in the search region.
Axionlike particles (ALPs) are hypothetical light (sub-eV) bosons predicted in some extensions of the Standard Model of particle physics. In astrophysical environments comprising high-energy gamma rays and turbulent magnetic fields, the existence of ALPs can modify the energy spectrum of the gamma rays for a sufficiently large coupling between ALPs and photons. This modification would take the form of an irregular behavior of the energy spectrum in a limited energy range. Data from the H. E. S. S. observations of the distant BL Lac object PKS 2155 - 304 (z = 0.116) are used to derive upper limits at the 95% C. L. on the strength of the ALP coupling to photons, g(gamma a) < 2.1 x 10(-11) GeV-1 for an ALP mass between 15 and 60 neV. The results depend on assumptions on the magnetic field around the source, which are chosen conservatively. The derived constraints apply to both light pseudoscalar and scalar bosons that couple to the electromagnetic field.
Diffuse gamma-ray emission is the most prominent observable signature of celestial cosmic-ray interactions at high energies. While already being investigated at GeVenergies over several decades, assessments of diffuse gamma-ray emission at TeVenergies remain sparse. After completion of the systematic survey of the inner Galaxy, the H.E.S.S. experiment is in a prime position to observe large-scale diffuse emission at TeVenergies. Data of the H.E.S.S. Galactic Plane Survey are investigated in regions off known gamma-ray sources. Corresponding gamma-ray flux measurements were made over an extensive grid of celestial locations. Longitudinal and latitudinal profiles of the observed gamma-ray fluxes show characteristic excess emission not attributable to known gamma-ray sources. For the first time large-scale gamma-ray emission along the Galactic plane using imaging atmospheric Cherenkov telescopes has been observed. While the background subtraction technique limits the ability to recover modest variation on the scale of the H.E.S.S. field of view or larger, which is characteristic of the inverse Compton scatter-induced Galactic diffuse emission, contributions of neutral pion decay as well as emission from unresolved gamma-ray sources can be recovered in the observed signal to a large fraction. Calculations show that the minimum gamma-ray emission from pi(0) decay represents a significant contribution to the total signal. This detection is interpreted as a mix of diffuse Galactic gamma-ray emission and unresolved sources.
Discovery of high and very high-energy emission from the BL Lacertae object SHBL J001355.9-185406
(2013)
The detection of the high-frequency peaked BL Lac object (HBL) SHBL J001355.9-185406 (z = 0.095) at high (HE; 100 MeV < E < 300 GeV) and very high-energy (VHE; E > 100 GeV) with the Fermi Large Area Telescope (LAT) and the High Energy Stereoscopic System (H.E.S.S.) is reported. Dedicated observations were performed with the H. E. S. S. telescopes, leading to a detection at the 5.5 sigma significance level. The measured flux above 310 GeV is (8.3 +/- 1.7(stat) +/- 1.7(sys)) x 10(-13) photons cm(-2) s(-1) (about 0.6% of that of the Crab Nebula), and the power-law spectrum has a photon index of Gamma = 3.4 +/- 0.5(stat) +/- 0.2(sys). Using 3.5 years of publicly available Fermi-LAT data, a faint counterpart has been detected in the LAT data at the 5.5 sigma significance level, with an integrated flux above 300 MeV of (9.3 +/- 3.4(stat) +/- 0.8(sys)) x 10(-10) photons cm(-2) s(-1) and a photon index of Gamma = 1.96 +/- 0.20(stat) +/- 0.08(sys). X-ray observations with Swift-XRT allow the synchrotron peak energy in vF(v) representation to be located at similar to 1.0 keV. The broadband spectral energy distribution is modelled with a one-zone synchrotron self-Compton (SSC) model and the optical data by a black-body emission describing the thermal emission of the host galaxy. The derived parameters are typical of HBLs detected at VHE, with a particle-dominated jet.
Very high-energy gamma-ray emission from PKS 0447-439 was detected with the H. E. S. S. Cherenkov telescope array in December 2009. This blazar is one of the brightest extragalactic objects in the Fermi bright source list and has a hard spectrum in the MeV to GeV range. In the TeV range, a photon index of 3.89 +/- 0.37 (stat) +/- 0.22 (sys) and a flux normalisation at 1 TeV, phi(1) (TeV) = (3.5 +/- 1.1(stat) +/- 0.9(sys)) x 10(-13) cm(-2) s(-1) TeV-1 were found. The detection with H. E. S. S. triggered observations in the X-ray band with the Swift and RXTE telescopes. Simultaneous UV and optical data from Swift UVOT and data from the optical telescopes ATOM and ROTSE are also available. The spectrum and light curve measured with H. E. S. S. are presented and compared to the multi-wavelength data at lower energies. A rapid flare is seen in the Swift XRT and RXTE data, together with a flux variation in the UV band, at a time scale of the order of one day. A firm upper limit of z < 0.59 on the redshift of PKS 0447-439 is derived from the combined Fermi-LAT and H. E. S. S. data, given the assumptions that there is no upturn in the intrinsic spectrum above the Fermi-LAT energy range and that absorption on the extragalactic background light (EBL) is not weaker than the lower limit provided by current models. The spectral energy distribution is well described by a simple one-zone synchrotron self-Compton scenario, if the redshift of the source is less than z less than or similar to 0.4.
This Letter reports the discovery of a remarkably hard spectrum source, HESS J1641-463, by the High Energy Stereoscopic System (H.E.S.S.) in the very high energy (VHE) domain. HESS J1641-463 remained unnoticed by the usual analysis techniques due to confusion with the bright nearby source HESS J1640-465. It emerged at a significance level of 8.5 standard deviations after restricting the analysis to events with energies above 4 TeV. It shows a moderate flux level of phi(E > 1TeV) = (3.64 +/- 0.44(stat)+/- 0.73(sys)) x 10(-13) cm(-2) s(-1), corresponding to 1.8% of the Crab Nebula flux above the same energy, and a hard spectrum with a photon index of Gamma = 2.07 +/- 0.11(stat)+/- 0.20(sys). It is a point-like source, although an extension up to a Gaussian width of sigma = 3 arcmin cannot be discounted due to uncertainties in the H.E.S.S. point-spread function. The VHE gamma-ray flux of HESS J1641-463 is found to be constant over the observed period when checking time binnings from the year-by-year to the 28 minute exposure timescales. HESS J1641-463 is positionally coincident with the radio supernova remnant SNR G338.5+0.1. No X-ray candidate stands out as a clear association; however, Chandra and XMM-Newton data reveal some potential weak counterparts. Various VHE gamma-ray production scenarios are discussed. If the emission from HESS J1641-463 is produced by cosmic ray protons colliding with the ambient gas, then their spectrum must extend close to 1 PeV. This object may represent a source population contributing significantly to the galactic cosmic ray flux around the knee.
Discovery of very high energy gamma-ray emission from the BL Lacertae
object PKS0301-243 with HESS
(2013)
The active galactic nucleus PKS 0301-243 (z = 0.266) is a high-synchrotron-peaked BL Lac object that is detected at high energies (HE, 100 MeV < E < 100 GeV) by Fermi/LAT. This paper reports on the discovery of PKS 0301-243 at very high energies (E > 100 GeV) by the High Energy Stereoscopic System (H.E.S.S.) from observations between September 2009 and December 2011 for a total live time of 34.9 h. Gamma rays above 200 GeV are detected at a significance of 9.4 sigma. A hint of variability at the 2.5 sigma level is found. An integral flux I(E > 200GeV) = (3.3 +/- 1.1(stat) +/- 0.7(syst)) x 10(-12) ph cm(-2) s(-1) and a photon index Gamma = 4.6 +/- 0.7(stat) +/- 0.2(syst) are measured. Multi-wavelength light curves in HE, X-ray and optical bands show strong variability, and a minimal variability timescale of eight days is estimated from the optical light curve. A single-zone leptonic synchrotron self-Compton scenario satisfactorily reproduces the multi-wavelength data. In this model, the emitting region is out of equipartition and the jet is particle dominated. Because of its high redshift compared to other sources observed at TeV energies, the very high energy emission from PKS 0301-243 is attenuated by the extragalactic background light (EBL) and the measured spectrum is used to derive an upper limit on the opacity of the EBL.