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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.
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.
During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Context. Over the past 20 yr, the quietest areas of the solar surface have revealed a weak but extremely dynamic magnetism occurring at small scales (<500 km), which may provide an important contribution to the dynamics and energetics of the outer layers of the atmosphere. Understanding this magnetism requires the inference of physical quantities from high-sensitivity spectro-polarimetric data with high spatio-temporal resolution. Aims. We present high-precision spectro-polarimetric data with high spatial resolution (0.4") of the very quiet Sun at 1.56 mu m obtained with the GREGOR telescope to shed some light on this complex magnetism. Methods. We used inversion techniques in two main approaches. First, we assumed that the observed profiles can be reproduced with a constant magnetic field atmosphere embedded in a field-free medium. Second, we assumed that the resolution element has a substructure with either two constant magnetic atmospheres or a single magnetic atmosphere with gradients of the physical quantities along the optical depth, both coexisting with a global stray-light component. Results. Half of our observed quiet-Sun region is better explained by magnetic substructure within the resolution element. However, we cannot distinguish whether this substructure comes from gradients of the physical parameters along the line of sight or from horizontal gradients (across the surface). In these pixels, a model with two magnetic components is preferred, and we find two distinct magnetic field populations. The population with the larger filling factor has very weak (similar to 150 G) horizontal fields similar to those obtained in previous works. We demonstrate that the field vector of this population is not constrained by the observations, given the spatial resolution and polarimetric accuracy of our data. The topology of the other component with the smaller filling factor is constrained by the observations for field strengths above 250 G: we infer hG fields with inclinations and azimuth values compatible with an isotropic distribution. The filling factors are typically below 30%. We also find that the flux of the two polarities is not balanced. From the other half of the observed quiet-Sun area similar to 50% are two-lobed Stokes V profiles, meaning that 23% of the field of view can be adequately explained with a single constant magnetic field embedded in a non-magnetic atmosphere. The magnetic field vector and filling factor are reliable inferred in only 50% based on the regular profiles. Therefore, 12% of the field of view harbour hG fields with filling factors typically below 30%. At our present spatial resolution, 70% of the pixels apparently are non-magnetised.
Arch filament systems occur in active sunspot groups, where a fibril structure connects areas of opposite magnetic polarity, in contrast to active region filaments that follow the polarity inversion line. We used the GREGOR Infrared Spectrograph (GRIS) to obtain the full Stokes vector in the spectral lines SiI lambda 1082.7 nm, He I lambda 1083.0 nm, and Ca I lambda 1083.9 nm. We focus on the near-infrared calcium line to investigate the photospheric magnetic field and velocities, and use the line core intensities and velocities of the helium line to study the chromospheric plasma. The individual fibrils of the arch filament system connect the sunspot with patches of magnetic polarity opposite to that of the spot. These patches do not necessarily coincide with pores, where the magnetic field is strongest. Instead, areas are preferred not far from the polarity inversion line. These areas exhibit photospheric downflows of moderate velocity, but significantly higher downflows of up to 30 km s(-1) in the chromospheric helium line. Our findings can be explained with new emerging flux where the matter flows downward along the field lines of rising flux tubes, in agreement with earlier results. (C) 2016 WILEY-VCH Verlag GmbH& Co. KGaA, Weinheim
Context. The solar magnetic field is responsible for all aspects of solar activity. Thus, emergence of magnetic flux at the surface is the first manifestation of the ensuing solar activity. Aims. Combining high-resolution and synoptic observations aims to provide a comprehensive description of flux emergence at photospheric level and of the growth process that eventually leads to a mature active region. Methods. The small active region NOAA 12118 emerged on 2014 July 17 and was observed one day later with the 1.5-m GREGOR solar telescope on 2014 July 18. High-resolution time-series of blue continuum and G-band images acquired in the blue imaging channel (BIC) of the GREGOR Fabry-Perot Interferometer (GFPI) were complemented by synoptic line-of-sight magnetograms and continuum images obtained with the Helioseismic and Magnetic Imager (HMI) onboard the Solar Dynamics Observatory (SDO). Horizontal proper motions and horizontal plasma velocities were computed with local correlation tracking (LCT) and the differential affine velocity estimator (DAVE), respectively. Morphological image processing was employed to measure the photometric and magnetic area, magnetic flux, and the separation profile of the emerging flux region during its evolution. Results. The computed growth rates for photometric area, magnetic area, and magnetic flux are about twice as high as the respective decay rates. The space-time diagram using HMI magnetograms of five days provides a comprehensive view of growth and decay. It traces a leaf-like structure, which is determined by the initial separation of the two polarities, a rapid expansion phase, a time when the spread stalls, and a period when the region slowly shrinks again. The separation rate of 0.26 km s(-1) is highest in the initial stage, and it decreases when the separation comes to a halt. Horizontal plasma velocities computed at four evolutionary stages indicate a changing pattern of inflows. In LCT maps we find persistent flow patterns such as outward motions in the outer part of the two major pores, a diverging feature near the trailing pore marking the site of upwelling plasma and flux emergence, and low velocities in the interior of dark pores. We detected many elongated rapidly expanding granules between the two major polarities, with dimensions twice as large as the normal granules.
Introducing the CTA concept
(2013)
The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project.
Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.