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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.
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.
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.
Exploring, exploiting and evolving diversity of aquatic ecosystem models: a community perspective
(2015)
Here, we present a community perspective on how to explore, exploit and evolve the diversity in aquatic ecosystem models. These models play an important role in understanding the functioning of aquatic ecosystems, filling in observation gaps and developing effective strategies for water quality management. In this spirit, numerous models have been developed since the 1970s. We set off to explore model diversity by making an inventory among 42 aquatic ecosystem modellers, by categorizing the resulting set of models and by analysing them for diversity. We then focus on how to exploit model diversity by comparing and combining different aspects of existing models. Finally, we discuss how model diversity came about in the past and could evolve in the future. Throughout our study, we use analogies from biodiversity research to analyse and interpret model diversity. We recommend to make models publicly available through open-source policies, to standardize documentation and technical implementation of models, and to compare models through ensemble modelling and interdisciplinary approaches. We end with our perspective on how the field of aquatic ecosystem modelling might develop in the next 5-10 years. To strive for clarity and to improve readability for non-modellers, we include a glossary.
High-resolution surface velocities and strain for Anatolia from Sentinel-1 InSAR and GNSS data
(2020)
Measurements of present-day surface deformation are essential for the assessment of long-term seismic hazard. The European Space Agency's Sentinel-1 satellites enable global, high-resolution observation of crustal motion from Interferometric Synthetic Aperture Radar (InSAR). We have developed automated InSAR processing systems that exploit the first similar to 5 years of Sentinel-1 data to measure surface motions for the similar to 800,000-km(2) Anatolian region. Our new 3-D velocity and strain rate fields illuminate deformation patterns dominated by westward motion of Anatolia relative to Eurasia, localized strain accumulation along the North and East Anatolian Faults, and rapid vertical signals associated with anthropogenic activities and to a lesser extent extension across the grabens of western Anatolia. We show that automatically processed Sentinel-1 InSAR data can characterize details of the velocity and strain rate fields with high resolution and accuracy over large regions. These results are important for assessing the relationship between strain accumulation and release in earthquakes. <br /> Plain Language Summary Satellite-based measurements of small rates of motion of the Earth's surface made at high spatial resolutions and over large areas are important for many geophysical applications including improving earthquake hazard models. We take advantage of recent advances in geodetic techniques in order to measure surface velocities and tectonic strain accumulation across the Anatolia region, including the highly seismogenic and often deadly North Anatolian Fault. We show that by combining Sentinel-1 Interferometric Synthetic Aperture Radar (InSAR) data with Global Navigation Satellite System (GNSS) measurements we can enhance our view of surface deformation associated with active tectonics, the earthquake cycle, and anthropogenic processes.
Climate change and its impacts already pose considerable challenges for societies that will further increase with global warming (IPCC, 2014a, b). Uncertainties of the climatic response to greenhouse gas emissions include the potential passing of large-scale tipping points (e.g. Lenton et al., 2008; Levermann et al., 2012; Schellnhuber, 2010) and changes in extreme meteorological events (Field et al., 2012) with complex impacts on societies (Hallegatte et al., 2013). Thus climate change mitigation is considered a necessary societal response for avoiding uncontrollable impacts (Conference of the Parties, 2010). On the other hand, large-scale climate change mitigation itself implies fundamental changes in, for example, the global energy system. The associated challenges come on top of others that derive from equally important ethical imperatives like the fulfilment of increasing food demand that may draw on the same resources. For example, ensuring food security for a growing population may require an expansion of cropland, thereby reducing natural carbon sinks or the area available for bio-energy production. So far, available studies addressing this problem have relied on individual impact models, ignoring uncertainty in crop model and biome model projections. Here, we propose a probabilistic decision framework that allows for an evaluation of agricultural management and mitigation options in a multi-impact-model setting. Based on simulations generated within the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP), we outline how cross-sectorally consistent multi-model impact simulations could be used to generate the information required for robust decision making.
Using an illustrative future land use pattern, we discuss the trade-off between potential gains in crop production and associated losses in natural carbon sinks in the new multiple crop-and biome-model setting. In addition, crop and water model simulations are combined to explore irrigation increases as one possible measure of agricultural intensification that could limit the expansion of cropland required in response to climate change and growing food demand. This example shows that current impact model uncertainties pose an important challenge to long-term mitigation planning and must not be ignored in long-term strategic decision making.
The 11 July 1889 Chilik earthquake (M-w 8.0-8.3) forms part of a remarkable sequence of large earthquakes in the late nineteenth and early twentieth centuries in the northern Tien Shan. Despite its importance, the source of the 1889 earthquake remains unknown, though the macroseismic epicenter is sited in the Chilik valley, similar to 100 km southeast of Almaty, Kazakhstan (similar to 2 million population). Several short fault segments that have been inferred to have ruptured in 1889 are too short on their own to account for the estimated magnitude. In this paper we perform detailed surveying and trenching of the similar to 30 km long Saty fault, one of the previously inferred sources, and find that it was formed in a single earthquake within the last 700 years, involving surface slip of up to 10 m. The scarp-forming event, likely to be the 1889 earthquake, was the only surface-rupturing event for at least 5000 years and potentially for much longer. From satellite imagery we extend the mapped length of fresh scarps within the 1889 epicentral zone to a total of similar to 175 km, which we also suggest as candidate ruptures from the 1889 earthquake. The 175 km of rupture involves conjugate oblique left-lateral and right-lateral slip on three separate faults, with step overs of several kilometers between them. All three faults were essentially invisible in the Holocene geomorphology prior to the last slip. The recurrence interval between large earthquakes on any of these faults, and presumably on other faults of the Tien Shan, may be longer than the timescale over which the landscape is reset, providing a challenge for delineating sources of future hazard.
A large number and wide variety of lake ecosystem models have been developed and published during the past four decades. We identify two challenges for making further progress in this field. One such challenge is to avoid developing more models largely following the concept of others ('reinventing the wheel'). The other challenge is to avoid focusing on only one type of model, while ignoring new and diverse approaches that have become available ('having tunnel vision'). In this paper, we aim at improving the awareness of existing models and knowledge of concurrent approaches in lake ecosystem modelling, without covering all possible model tools and avenues. First, we present a broad variety of modelling approaches. To illustrate these approaches, we give brief descriptions of rather arbitrarily selected sets of specific models. We deal with static models (steady state and regression models), complex dynamic models (CAEDYM, CE-QUAL-W2, Delft 3D-ECO, LakeMab, LakeWeb, MyLake, PCLake, PROTECH, SALMO), structurally dynamic models and minimal dynamic models. We also discuss a group of approaches that could all be classified as individual based: super-individual models (Piscator, Charisma), physiologically structured models, stage-structured models and traitbased models. We briefly mention genetic algorithms, neural networks, Kalman filters and fuzzy logic. Thereafter, we zoom in, as an in-depth example, on the multi-decadal development and application of the lake ecosystem model PCLake and related models (PCLake Metamodel, Lake Shira Model, IPH-TRIM3D-PCLake). In the discussion, we argue that while the historical development of each approach and model is understandable given its 'leading principle', there are many opportunities for combining approaches. We take the point of view that a single 'right' approach does not exist and should not be strived for. Instead, multiple modelling approaches, applied concurrently to a given problem, can help develop an integrative view on the functioning of lake ecosystems. We end with a set of specific recommendations that may be of help in the further development of lake ecosystem models.
A large number and wide variety of lake ecosystem models have been developed and published during the past four decades. We identify two challenges for making further progress in this field. One such challenge is to avoid developing more models largely following the concept of others ('reinventing the wheel'). The other challenge is to avoid focusing on only one type of model, while ignoring new and diverse approaches that have become available ('having tunnel vision'). In this paper, we aim at improving the awareness of existing models and knowledge of concurrent approaches in lake ecosystem modelling, without covering all possible model tools and avenues. First, we present a broad variety of modelling approaches. To illustrate these approaches, we give brief descriptions of rather arbitrarily selected sets of specific models. We deal with static models (steady state and regression models), complex dynamic models (CAEDYM, CE-QUAL-W2, Delft 3D-ECO, LakeMab, LakeWeb, MyLake, PCLake, PROTECH, SALMO), structurally dynamic models and minimal dynamic models. We also discuss a group of approaches that could all be classified as individual based: super-individual models (Piscator, Charisma), physiologically structured models, stage-structured models and traitbased models. We briefly mention genetic algorithms, neural networks, Kalman filters and fuzzy logic. Thereafter, we zoom in, as an in-depth example, on the multi-decadal development and application of the lake ecosystem model PCLake and related models (PCLake Metamodel, Lake Shira Model, IPH-TRIM3D-PCLake). In the discussion, we argue that while the historical development of each approach and model is understandable given its 'leading principle', there are many opportunities for combining approaches. We take the point of view that a single 'right' approach does not exist and should not be strived for. Instead, multiple modelling approaches, applied concurrently to a given problem, can help develop an integrative view on the functioning of lake ecosystems. We end with a set of specific recommendations that may be of help in the further development of lake ecosystem models.
Climate change and its impacts already pose considerable challenges for societies that will further increase with global warming (IPCC, 2014a, b). Uncertainties of the climatic response to greenhouse gas emissions include the potential passing of large-scale tipping points (e.g. Lenton et al., 2008; Levermann et al., 2012; Schellnhuber, 2010) and changes in extreme meteorological events (Field et al., 2012) with complex impacts on societies (Hallegatte et al., 2013). Thus climate change mitigation is considered a necessary societal response for avoiding uncontrollable impacts (Conference of the Parties, 2010). On the other hand, large-scale climate change mitigation itself implies fundamental changes in, for example, the global energy system. The associated challenges come on top of others that derive from equally important ethical imperatives like the fulfilment of increasing food demand that may draw on the same resources. For example, ensuring food security for a growing population may require an expansion of cropland, thereby reducing natural carbon sinks or the area available for bio-energy production. So far, available studies addressing this problem have relied on individual impact models, ignoring uncertainty in crop model and biome model projections. Here, we propose a probabilistic decision framework that allows for an evaluation of agricultural management and mitigation options in a multi-impact-model setting. Based on simulations generated within the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP), we outline how cross-sectorally consistent multi-model impact simulations could be used to generate the information required for robust decision making.
Using an illustrative future land use pattern, we discuss the trade-off between potential gains in crop production and associated losses in natural carbon sinks in the new multiple crop-and biome-model setting. In addition, crop and water model simulations are combined to explore irrigation increases as one possible measure of agricultural intensification that could limit the expansion of cropland required in response to climate change and growing food demand. This example shows that current impact model uncertainties pose an important challenge to long-term mitigation planning and must not be ignored in long-term strategic decision making.
LiCSBAS
(2020)
For the past five years, the 2-satellite Sentinel-1 constellation has provided abundant and useful Synthetic Aperture Radar (SAR) data, which have the potential to reveal global ground surface deformation at high spatial and temporal resolutions. However, for most users, fully exploiting the large amount of associated data is challenging, especially over wide areas. To help address this challenge, we have developed LiCSBAS, an open-source SAR interferometry (InSAR) time series analysis package that integrates with the automated Sentinel-1 InSAR processor (LiCSAR). LiCSBAS utilizes freely available LiCSAR products, and users can save processing time and disk space while obtaining the results of InSAR time series analysis. In the LiCSBAS processing scheme, interferograms with many unwrapping errors are automatically identified by loop closure and removed. Reliable time series and velocities are derived with the aid of masking using several noise indices. The easy implementation of atmospheric corrections to reduce noise is achieved with the Generic Atmospheric Correction Online Service for InSAR (GACOS). Using case studies in southern Tohoku and the Echigo Plain, Japan, we demonstrate that LiCSBAS applied to LiCSAR products can detect both large-scale (>100 km) and localized (~km) relative displacements with an accuracy of <1 cm/epoch and ~2 mm/yr. We detect displacements with different temporal characteristics, including linear, periodic, and episodic, in Niigata, Ojiya, and Sanjo City, respectively. LiCSBAS and LiCSAR products facilitate greater exploitation of globally available and abundant SAR datasets and enhance their applications for scientific research and societal benefit.
LiCSBAS
(2020)
For the past five years, the 2-satellite Sentinel-1 constellation has provided abundant and useful Synthetic Aperture Radar (SAR) data, which have the potential to reveal global ground surface deformation at high spatial and temporal resolutions. However, for most users, fully exploiting the large amount of associated data is challenging, especially over wide areas. To help address this challenge, we have developed LiCSBAS, an open-source SAR interferometry (InSAR) time series analysis package that integrates with the automated Sentinel-1 InSAR processor (LiCSAR). LiCSBAS utilizes freely available LiCSAR products, and users can save processing time and disk space while obtaining the results of InSAR time series analysis. In the LiCSBAS processing scheme, interferograms with many unwrapping errors are automatically identified by loop closure and removed. Reliable time series and velocities are derived with the aid of masking using several noise indices. The easy implementation of atmospheric corrections to reduce noise is achieved with the Generic Atmospheric Correction Online Service for InSAR (GACOS). Using case studies in southern Tohoku and the Echigo Plain, Japan, we demonstrate that LiCSBAS applied to LiCSAR products can detect both large-scale (>100 km) and localized (similar to km) relative displacements with an accuracy of <1 cm/epoch and similar to 2 mm/yr. We detect displacements with different temporal characteristics, including linear, periodic, and episodic, in Niigata, Ojiya, and Sanjo City, respectively. LiCSBAS and LiCSAR products facilitate greater exploitation of globally available and abundant SAR datasets and enhance their applications for scientific research and societal benefit.