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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.
Many widely used observational data sets are comprised of several overlapping instrument records. While data inter-calibration techniques often yield continuous and reliable data for trend analysis, less attention is generally paid to maintaining higher-order statistics such as variance and autocorrelation. A growing body of work uses these metrics to quantify the stability or resilience of a system under study and potentially to anticipate an approaching critical transition in the system. Exploring the degree to which changes in resilience indicators such as the variance or autocorrelation can be attributed to non-stationary characteristics of the measurement process – rather than actual changes in the dynamical properties of the system – is important in this context. In this work we use both synthetic and empirical data to explore how changes in the noise structure of a data set are propagated into the commonly used resilience metrics lag-one autocorrelation and variance. We focus on examples from remotely sensed vegetation indicators such as vegetation optical depth and the normalized difference vegetation index from different satellite sources. We find that time series resulting from mixing signals from sensors with varied uncertainties and covering overlapping time spans can lead to biases in inferred resilience changes. These biases are typically more pronounced when resilience metrics are aggregated (for example, by land-cover type or region), whereas estimates for individual time series remain reliable at reasonable sensor signal-to-noise ratios. Our work provides guidelines for the treatment and aggregation of multi-instrument data in studies of critical transitions and resilience.
Many widely used observational data sets are comprised of several overlapping instrument records. While data inter-calibration techniques often yield continuous and reliable data for trend analysis, less attention is generally paid to maintaining higher-order statistics such as variance and autocorrelation. A growing body of work uses these metrics to quantify the stability or resilience of a system under study and potentially to anticipate an approaching critical transition in the system. Exploring the degree to which changes in resilience indicators such as the variance or autocorrelation can be attributed to non-stationary characteristics of the measurement process – rather than actual changes in the dynamical properties of the system – is important in this context. In this work we use both synthetic and empirical data to explore how changes in the noise structure of a data set are propagated into the commonly used resilience metrics lag-one autocorrelation and variance. We focus on examples from remotely sensed vegetation indicators such as vegetation optical depth and the normalized difference vegetation index from different satellite sources. We find that time series resulting from mixing signals from sensors with varied uncertainties and covering overlapping time spans can lead to biases in inferred resilience changes. These biases are typically more pronounced when resilience metrics are aggregated (for example, by land-cover type or region), whereas estimates for individual time series remain reliable at reasonable sensor signal-to-noise ratios. Our work provides guidelines for the treatment and aggregation of multi-instrument data in studies of critical transitions and resilience.
The Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2) with its land and vegetation height data product (ATL08), and Global Ecosystem Dynamics Investigation (GEDI) with its terrain elevation and height metrics data product (GEDI Level 2A) missions have great potential to globally map ground and canopy heights. Canopy height is a key factor in estimating above-ground biomass and its seasonal changes; these satellite missions can also improve estimated above-ground carbon stocks. This study presents a novel Sparse Vegetation Detection Algorithm (SVDA) which uses ICESat-2 (ATL03, geolocated photons) data to map tree and vegetation heights in a sparsely vegetated savanna ecosystem. The SVDA consists of three main steps: First, noise photons are filtered using the signal confidence flag from ATL03 data and local point statistics. Second, we classify ground photons based on photon height percentiles. Third, tree and grass photons are classified based on the number of neighbors. We validated tree heights with field measurements (n = 55), finding a root-mean-square error (RMSE) of 1.82 m using SVDA, GEDI Level 2A (Geolocated Elevation and Height Metrics product): 1.33 m, and ATL08: 5.59 m. Our results indicate that the SVDA is effective in identifying canopy photons in savanna ecosystems, where ATL08 performs poorly. We further identify seasonal vegetation height changes with an emphasis on vegetation below 3 m; widespread height changes in this class from two wet-dry cycles show maximum seasonal changes of 1 m, possibly related to seasonal grass-height differences. Our study shows the difficulties of vegetation measurements in savanna ecosystems but provides the first estimates of seasonal biomass changes.
The Upper Indus Basin (UIB), which covers a wide range of climatic and topographic settings, provides an ideal venue to explore the relationship between climate and topography. While the distribution of snow and glaciers is spatially and temporally heterogeneous, there exist regions with similar elevation-snow relationships. In this work, we construct elevation-binned snow-cover statistics to analyze 3415 watersheds and 7357 glaciers in the UIB region. We group both glaciers and watersheds using a hierarchical clustering approach and find that (1) watershed clusters mirror large-scale moisture transport patterns and (2) are highly dependent on median watershed elevation. (3) Glacier clusters are spatially heterogeneous and are less strongly controlled by elevation, but rather by local topographic parameters that modify solar insolation. Our clustering approach allows us to clearly define self-similar snow-topographic regions. Eastern watersheds in the UIB show a steep snow cover-elevation relationship whereas watersheds in the central and western UIB have moderately sloped relationships, but cluster in distinct groups. We highlight this snow-cover-topographic transition zone and argue that these watersheds have different hydrologic responses than other regions. Our hierarchical clustering approach provides a potential new framework to use in defining climatic zones in the cyrosphere based on empirical data.
Insolation differences play a primary role in controlling microclimate and vegetation cover, which together influence the development of topography. Topographic asymmetry (TA), or slope differences between terrain aspects, has been well documented in small-scale, field-based, and modeling studies. Here we combine a suite of environmental (e.g., vegetation, temperature, solar insolation) and topographic (e.g., elevation, drainage network) data to explore the driving mechanisms and markers of TA on a global scale. Using a novel empirical TA analysis method, we find that (1) steeper terrain has higher TA magnitudes, (2) globally, pole-facing terrain is on average steeper than equator-facing terrain, especially in mid-latitude, tectonically quiescent, and vegetated landscapes, and (3) high-elevation and low-temperature regions tend to have terrain steepened toward the equator. We further show that there are distinct differences in climate and vegetation cover across terrain aspects, and that TA is reflected in the size and form of fluvial drainage networks. Our work supports the argument that insolation asymmetries engender differences in local microclimates and vegetation on opposing terrain aspects, which broadly encourage the development of asymmetric topography across a range of lithologic, tectonic, geomorphic, and climatic settings.
The Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2) with its land and vegetation height data product (ATL08), and Global Ecosystem Dynamics Investigation (GEDI) with its terrain elevation and height metrics data product (GEDI Level 2A) missions have great potential to globally map ground and canopy heights. Canopy height is a key factor in estimating above-ground biomass and its seasonal changes; these satellite missions can also improve estimated above-ground carbon stocks. This study presents a novel Sparse Vegetation Detection Algorithm (SVDA) which uses ICESat-2 (ATL03, geolocated photons) data to map tree and vegetation heights in a sparsely vegetated savanna ecosystem. The SVDA consists of three main steps: First, noise photons are filtered using the signal confidence flag from ATL03 data and local point statistics. Second, we classify ground photons based on photon height percentiles. Third, tree and grass photons are classified based on the number of neighbors. We validated tree heights with field measurements (n = 55), finding a root-mean-square error (RMSE) of 1.82 m using SVDA, GEDI Level 2A (Geolocated Elevation and Height Metrics product): 1.33 m, and ATL08: 5.59 m. Our results indicate that the SVDA is effective in identifying canopy photons in savanna ecosystems, where ATL08 performs poorly. We further identify seasonal vegetation height changes with an emphasis on vegetation below 3 m; widespread height changes in this class from two wet-dry cycles show maximum seasonal changes of 1 m, possibly related to seasonal grass-height differences. Our study shows the difficulties of vegetation measurements in savanna ecosystems but provides the first estimates of seasonal biomass changes.
High Mountain Asia (HMA) is dependent upon both the amount and timing of snow and glacier meltwater. Previous model studies and coarse resolution (0.25° × 0.25°, ∼25 km × 25 km) passive microwave assessments of trends in the volume and timing of snowfall, snowmelt, and glacier melt in HMA have identified key spatial and seasonal heterogeneities in the response of snow to changes in regional climate. Here we use recently developed, continuous, internally consistent, and high-resolution passive microwave data (3.125 km × 3.125 km, 1987–2016) from the special sensor microwave imager instrument family to refine and extend previous estimates of changes in the snow regime of HMA. We find an overall decline in snow volume across HMA; however, there exist spatially contiguous regions of increasing snow volume—particularly during the winter season in the Pamir, Karakoram, Hindu Kush, and Kunlun Shan. Detailed analysis of changes in snow-volume trends through time reveal a large step change from negative trends during the period 1987–1997, to much more positive trends across large regions of HMA during the periods 1997–2007 and 2007–2016. We also find that changes in high percentile monthly snow-water volume exhibit steeper trends than changes in low percentile snow-water volume, which suggests a reduction in the frequency of high snow-water volumes in much of HMA. Regions with positive snow-water storage trends generally correspond to regions of positive glacier mass balances.
High Mountain Asia (HMA) is dependent upon both the amount and timing of snow and glacier meltwater. Previous model studies and coarse resolution (0.25° × 0.25°, ∼25 km × 25 km) passive microwave assessments of trends in the volume and timing of snowfall, snowmelt, and glacier melt in HMA have identified key spatial and seasonal heterogeneities in the response of snow to changes in regional climate. Here we use recently developed, continuous, internally consistent, and high-resolution passive microwave data (3.125 km × 3.125 km, 1987–2016) from the special sensor microwave imager instrument family to refine and extend previous estimates of changes in the snow regime of HMA. We find an overall decline in snow volume across HMA; however, there exist spatially contiguous regions of increasing snow volume—particularly during the winter season in the Pamir, Karakoram, Hindu Kush, and Kunlun Shan. Detailed analysis of changes in snow-volume trends through time reveal a large step change from negative trends during the period 1987–1997, to much more positive trends across large regions of HMA during the periods 1997–2007 and 2007–2016. We also find that changes in high percentile monthly snow-water volume exhibit steeper trends than changes in low percentile snow-water volume, which suggests a reduction in the frequency of high snow-water volumes in much of HMA. Regions with positive snow-water storage trends generally correspond to regions of positive glacier mass balances.