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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 Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
(2019)
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
Large earthquakes initiate chains of surface processes that last much longer than the brief moments of strong shaking. Most moderate‐ and large‐magnitude earthquakes trigger landslides, ranging from small failures in the soil cover to massive, devastating rock avalanches. Some landslides dam rivers and impound lakes, which can collapse days to centuries later, and flood mountain valleys for hundreds of kilometers downstream. Landslide deposits on slopes can remobilize during heavy rainfall and evolve into debris flows. Cracks and fractures can form and widen on mountain crests and flanks, promoting increased frequency of landslides that lasts for decades. More gradual impacts involve the flushing of excess debris downstream by rivers, which can generate bank erosion and floodplain accretion as well as channel avulsions that affect flooding frequency, settlements, ecosystems, and infrastructure. Ultimately, earthquake sequences and their geomorphic consequences alter mountain landscapes over both human and geologic time scales. Two recent events have attracted intense research into earthquake‐induced landslides and their consequences: the magnitude M 7.6 Chi‐Chi, Taiwan earthquake of 1999, and the M 7.9 Wenchuan, China earthquake of 2008. Using data and insights from these and several other earthquakes, we analyze how such events initiate processes that change mountain landscapes, highlight research gaps, and suggest pathways toward a more complete understanding of the seismic effects on the Earth's surface.
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.
Local adaptation to different pollinators is considered one of the possible initial stages of ecological speciation as reproductive isolation is a by-product of the divergence in pollination systems. However, pollinator-mediated divergent selection will not necessarily result in complete reproductive isolation, because incipient speciation is often overcome by gene flow. We investigated the potential of pollinator shift in the sexually deceptive orchids Ophrys sphegodes and Ophrys exaltata and compared the levels of floral isolation vs. genetic distance among populations with contrasting predominant pollinators. We analysed floral hydrocarbons as a proxy for floral divergence between populations. Floral adoption of pollinators and their fidelity was tested using pollinator choice experiments. Interpopulation gene flow and population differentiation levels were estimated using AFLP markers. The Tyrrhenian O.sphegodes population preferentially attracted the pollinator bee Andrena bimaculata, whereas the Adriatic O.sphegodes population exclusively attracted A.nigroaenea. Significant differences in scent component proportions were identified in O.sphegodes populations that attracted different preferred pollinators. High interpopulation gene flow was detected, but populations were genetically structured at species level. The high interpopulation gene flow levels independent of preferred pollinators suggest that local adaptation to different pollinators has not (yet) generated detectable genome-wide separation. Alternatively, despite extensive gene flow, few genes underlying floral isolation remain differentiated as a consequence of divergent selection. Different pollination ecotypes in O.sphegodes might represent a local selective response imposed by temporal variation in a geographical mosaic of pollinators as a consequence of the frequent disturbance regimes typical of Ophrys habitats.
High topography in eastern Tibet is thought to have formed when deep crust beneath the central Tibetan Plateau flowed towards the plateau margin, causing crustal thickening and surface uplift(1,2). Rapid exhumation starting about 10-15 million years ago is inferred to mark the onset of surface uplift and fluvial incision(3-6). Although geophysical data are consistent with weak crust capable of flow(7,8), it is unclear how the timing(9) and amount of deformation adjacent to the Sichuan Basin during the Cenozoic era can be explained in this way(10,11). Here we use thermochronology to measure the cooling histories of rocks exposed in a section that stretches vertically over 3 km adjacent to the Sichuan Basin. Our thermal models of exhumation-driven cooling show that these rocks, and hence the plateau margin, were subject to slow, steady exhumation during early Cenozoic time, followed by two pulses of rapid exhumation, one beginning 30-25 million years ago and a second 10-15 million years ago that continues to present. Our findings imply that significant topographic relief existed adjacent to the Sichuan Basin before the Indo-Asian collision. Furthermore, the onset of Cenozoic mountain building probably pre-dated development of the weak lower crust, implying that early topography was instead formed during thickening of the upper crust along faults. We suggest that episodes of mountain building may reflect distinct geodynamic mechanisms of crustal thickening.
Historically, the giant panda was widely distributed from northern China to southwestern Asia [1]. As a result of range contraction and fragmentation, extant individuals are currently restricted to fragmented mountain ranges on the eastern margin of the Qinghai-Tibet plateau, where they are distributed among three major population clusters [2]. However, little is known about the genetic consequences of this dramatic range contraction. For example, were regions where giant pandas previously existed occupied by ancestors of present-day populations, or were these regions occupied by genetically distinct populations that are now extinct? If so, is there any contribution of these extinct populations to the genomes of giant pandas living today? To investigate these questions, we sequenced the nuclear genome of an similar to 5,000-year-old giant panda from Jiangdongshan, Teng-chong County in Yunnan Province, China. We find that this individual represents a genetically distinct population that diverged prior to the diversification of modern giant panda populations. We find evidence of differential admixture with this ancient population among modern individuals originating from different populations as well as within the same population. We also find evidence for directional gene flow, which transferred alleles from the ancient population into the modern giant panda lineages. A variable proportion of the genomes of extant individuals is therefore likely derived from the ancient population represented by our sequenced individual. Although extant giant panda populations retain reasonable genetic diversity, our results suggest that this represents only part of the genetic diversity this species harbored prior to its recent range contractions.