| 1. |
- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 2. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 3. |
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| 4. |
- Dima, Danai, et al.
(författare)
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Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
- 2022
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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| 5. |
- Ehrich, Dorothee, et al.
(författare)
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Documenting lemming population change in the Arctic : Can we detect trends?
- 2020
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 49:3, s. 786-800
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Tidskriftsartikel (refereegranskat)abstract
- Lemmings are a key component of tundra food webs and changes in their dynamics can affect the whole ecosystem. We present a comprehensive overview of lemming monitoring and research activities, and assess recent trends in lemming abundance across the circumpolar Arctic. Since 2000, lemmings have been monitored at 49 sites of which 38 are still active. The sites were not evenly distributed with notably Russia and high Arctic Canada underrepresented. Abundance was monitored at all sites, but methods and levels of precision varied greatly. Other important attributes such as health, genetic diversity and potential drivers of population change, were often not monitored. There was no evidence that lemming populations were decreasing in general, although a negative trend was detected for low arctic populations sympatric with voles. To keep the pace of arctic change, we recommend maintaining long-term programmes while harmonizing methods, improving spatial coverage and integrating an ecosystem perspective.
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| 6. |
- Foulger, Gillian R., et al.
(författare)
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The Iceland Microcontinent and a continental Greenland-Iceland-Faroe Ridge
- 2020
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Ingår i: Earth-Science Reviews. - : Elsevier BV. - 0012-8252 .- 1872-6828. ; 206
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Forskningsöversikt (refereegranskat)abstract
- The breakup of Laurasia to form the Northeast Atlantic Realm disintegrated an inhomogeneous collage of cratons sutured by cross-cutting orogens. Volcanic rifted margins formed that are underlain by magma-inflated, extended continental crust. North of the Greenland-Iceland-Faroe Ridge a new rift–the Aegir Ridge–propagated south along the Caledonian suture. South of the Greenland-Iceland-Faroe Ridge the proto-Reykjanes Ridge propagated north through the North Atlantic Craton along an axis displaced ~150 km to the west of the rift to the north. Both propagators stalled where the confluence of the Nagssugtoqidian and Caledonian orogens formed an ~300-km-wide transverse barrier. Thereafter, the ~150 × 300-km block of continental crust between the rift tips–the Iceland Microcontinent–extended in a distributed, unstable manner along multiple axes of extension. These axes repeatedly migrated or jumped laterally with shearing occurring between them in diffuse transfer zones. This style of deformation continues to the present day in Iceland. It is the surface expression of underlying magma-assisted stretching of ductile continental crust that has flowed from the Iceland Microplate and flanking continental areas to form the lower crust of the Greenland-Iceland-Faroe Ridge. Icelandic-type crust which underlies the Greenland-Iceland-Faroe Ridge is thus not anomalously thick oceanic crust as is often assumed. Upper Icelandic-type crust comprises magma flows and dykes. Lower Icelandic-type crust comprises magma-inflated continental mid- and lower crust. Contemporary magma production in Iceland, equivalent to oceanic layers 2–3, corresponds to Icelandic-type upper crust plus intrusions in the lower crust, and has a total thickness of only 10–15 km. This is much less than the total maximum thickness of 42 km for Icelandic-type crust measured seismically in Iceland. The feasibility of the structure we propose is confirmed by numerical modeling that shows extension of the continental crust can continue for many tens of millions of years by lower-crustal ductile flow. A composition of Icelandic-type lower crust that is largely continental can account for multiple seismic observations along with gravity, bathymetric, topographic, petrological and geochemical data that are inconsistent with a gabbroic composition for Icelandic-type lower crust. It also offers a solution to difficulties in numerical models for melt-production by downward-revising the amount of melt needed. Unstable tectonics on the Greenland-Iceland-Faroe Ridge can account for long-term tectonic disequilibrium on the adjacent rifted margins, the southerly migrating rift propagators that build diachronous chevron ridges of thick crust about the Reykjanes Ridge, and the tectonic decoupling of the oceans to the north and south. A model of complex, discontinuous continental breakup influenced by crustal inhomogeneity that distributes continental material in growing oceans fits other regions including the Davis Strait, the South Atlantic and the West Indian Ocean.
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| 7. |
- Frangou, Sophia, et al.
(författare)
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Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
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Tidskriftsartikel (refereegranskat)abstract
- Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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| 8. |
- Franke, James A, et al.
(författare)
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Agricultural breadbaskets shift poleward given adaptive farmer behavior under climate change
- 2022
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:1, s. 167-181
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Tidskriftsartikel (refereegranskat)abstract
- Modern food production is spatially concentrated in global "breadbaskets". A major unresolved question is whether these peak production regions will shift poleward as the climate warms, allowing some recovery of potential climaterelated losses. While agricultural impacts studies to date have focused on currently cultivated land, the Global Gridded Crop Model Intercomparison Project (GGCMI) Phase 2 experiment allows us to assess changes in both yields and the location of peak productivity regions under warming. We examine crop responses under projected end-of-century warming using 7 process-based models simulating 5 major crops (maize, rice, soybeans, and spring and winter wheat) with a variety of adaptation strategies. We find that in no-adaptation cases, when planting date and cultivar choices are held fixed, regions of peak production remain stationary and yield losses can be severe, since growing seasons contract strongly with warming. When adaptations in management practices are allowed (cultivars that retain growing season length under warming and modified planting dates), peak productivity zones shift poleward and yield losses are largely recovered. While most growing-zone shifts are ultimately limited by geography, breadbaskets studied here move poleward over 600 km on average by end of the century under RCP8.5. These results suggest that agricultural impacts assessments can be strongly biased if restricted in spatial area or in the scope of adaptive behavior considered. Accurate evaluation of food security under climate change requires global modeling and careful treatment of adaptation strategies.
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| 9. |
- Franke, James A., et al.
(författare)
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The GGCMI Phase 2 emulators : Global gridded crop model responses to changes in CO2, temperature, water, and nitrogen (version 1.0)
- 2020
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 13:9, s. 3995-4018
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Tidskriftsartikel (refereegranskat)abstract
- Statistical emulation allows combining advantageous features of statistical and process-based crop models for understanding the effects of future climate changes on crop yields. We describe here the development of emulators for nine process-based crop models and five crops using output from the Global Gridded Model Intercomparison Project (GGCMI) Phase 2. The GGCMI Phase 2 experiment is designed with the explicit goal of producing a structured training dataset for emulator development that samples across four dimensions relevant to crop yields: Atmospheric carbon dioxide (CO2) concentrations, temperature, water supply, and nitrogen inputs (CTWN). Simulations are run under two different adaptation assumptions: That growing seasons shorten in warmer climates, and that cultivar choice allows growing seasons to remain fixed. The dataset allows emulating the climatological-mean yield response of all models with a simple polynomial in mean growing-season values. Climatological-mean yields are a central metric in climate change impact analysis; we show here that they can be captured without relying on interannual variations. In general, emulation errors are negligible relative to differences across crop models or even across climate model scenarios; errors become significant only in some marginal lands where crops are not currently grown. We demonstrate that the resulting GGCMI emulators can reproduce yields under realistic future climate simulations, even though the GGCMI Phase 2 dataset is constructed with uniform CTWN offsets, suggesting that the effects of changes in temperature and precipitation distributions are small relative to those of changing means. The resulting emulators therefore capture relevant crop model responses in a lightweight, computationally tractable form, providing a tool that can facilitate model comparison, diagnosis of interacting factors affecting yields, and integrated assessment of climate impacts.
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| 10. |
- Franke, James A., et al.
(författare)
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The GGCMI Phase 2 experiment : Global gridded crop model simulations under uniform changes in CO2, temperature, water, and nitrogen levels (protocol version 1.0)
- 2020
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 13:5, s. 2315-2336
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Tidskriftsartikel (refereegranskat)abstract
- Concerns about food security under climate change motivate efforts to better understand future changes in crop yields. Process-based crop models, which represent plant physiological and soil processes, are necessary tools for this purpose since they allow representing future climate and management conditions not sampled in the historical record and new locations to which cultivation may shift. However, process-based crop models differ in many critical details, and their responses to different interacting factors remain only poorly understood. The Global Gridded Crop Model Intercomparison (GGCMI) Phase 2 experiment, an activity of the Agricultural Model Intercomparison and Improvement Project (AgMIP), is designed to provide a systematic parameter sweep focused on climate change factors and their interaction with overall soil fertility, to allow both evaluating model behavior and emulating model responses in impact assessment tools. In this paper we describe the GGCMI Phase 2 experimental protocol and its simulation data archive. A total of 12 crop models simulate five crops with systematic uniform perturbations of historical climate, varying CO2, temperature, water supply, and applied nitrogen ("CTWN") for rainfed and irrigated agriculture, and a second set of simulations represents a type of adaptation by allowing the adjustment of growing season length. We present some crop yield results to illustrate general characteristics of the simulations and potential uses of the GGCMI Phase 2 archive. For example, in cases without adaptation, modeled yields show robust decreases to warmer temperatures in almost all regions, with a nonlinear dependence that means yields in warmer baseline locations have greater temperature sensitivity. Inter-model uncertainty is qualitatively similar across all the four input dimensions but is largest in high-latitude regions where crops may be grown in the future.
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| 11. |
- Gorski, Mathias, et al.
(författare)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
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Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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| 12. |
- Gorski, Mathias, et al.
(författare)
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Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- 2021
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939
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Tidskriftsartikel (refereegranskat)abstract
- 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/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 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.
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| 13. |
- Müller, Christoph, et al.
(författare)
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Exploring uncertainties in global crop yield projections in a large ensemble of crop models and CMIP5 and CMIP6 climate scenarios
- 2021
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9318 .- 1748-9326. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Concerns over climate change are motivated in large part because of their impact on human society. Assessing the effect of that uncertainty on specific potential impacts is demanding, since it requires a systematic survey over both climate and impacts models. We provide a comprehensive evaluation of uncertainty in projected crop yields for maize, spring and winter wheat, rice, and soybean, using a suite of nine crop models and up to 45 CMIP5 and 34 CMIP6 climate projections for three different forcing scenarios. To make this task computationally tractable, we use a new set of statistical crop model emulators. We find that climate and crop models contribute about equally to overall uncertainty. While the ranges of yield uncertainties under CMIP5 and CMIP6 projections are similar, median impact in aggregate total caloric production is typically more negative for the CMIP6 projections (+1% to −19%) than for CMIP5 (+5% to −13%). In the first half of the 21st century and for individual crops is the spread across crop models typically wider than that across climate models, but we find distinct differences between crops: globally, wheat and maize uncertainties are dominated by the crop models, but soybean and rice are more sensitive to the climate projections. Climate models with very similar global mean warming can lead to very different aggregate impacts so that climate model uncertainties remain a significant contributor to agricultural impacts uncertainty. These results show the utility of large-ensemble methods that allow comprehensively evaluating factors affecting crop yields or other impacts under climate change. The crop model ensemble used here is unbalanced and pulls the assumption that all projections are equally plausible into question. Better methods for consistent model testing, also at the level of individual processes, will have to be developed and applied by the crop modeling community.
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| 14. |
- Müller, Christoph, et al.
(författare)
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Substantial Differences in Crop Yield Sensitivities Between Models Call for Functionality-Based Model Evaluation
- 2024
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Ingår i: Earth's Future. - 2328-4277. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Crop models are often used to project future crop yield under climate and global change and typically show a broad range of outcomes. To understand differences in modeled responses, we analyzed modeled crop yield response types using impact response surfaces along four drivers of crop yield: carbon dioxide (C), temperature (T), water (W), and nitrogen (N). Crop yield response types help to understand differences in simulated responses per driver and their combinations rather than aggregated changes in yields as the result of simultaneous changes in various drivers. We find that models' sensitivities to the individual drivers are substantially different and often more different across models than across regions. There is some agreement across models with respect to the spatial patterns of response types but strong differences in the distribution of response types across models and their configurations suggests that models need to undergo further scrutiny. We suggest establishing standards in model evaluation based on emergent functionality not only against historical yield observations but also against dedicated experiments across different drivers to analyze emergent functional patterns of crop models.
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| 15. |
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| 16. |
- Schijven, Dick, et al.
(författare)
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Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
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Tidskriftsartikel (refereegranskat)abstract
- Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
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| 17. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 18. |
- Taylor, Jason J., et al.
(författare)
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Arctic terrestrial biodiversity status and trends: A synopsis of science supporting the CBMP State of Arctic Terrestrial Biodiversity Report
- 2020
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 49:3, s. 833-847
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Tidskriftsartikel (refereegranskat)abstract
- This review provides a synopsis of the main findings of individual papers in the special issue Terrestrial Biodiversity in a Rapidly Changing Arctic. The special issue was developed to inform the State of the Arctic Terrestrial Biodiversity Report developed by the Circumpolar Biodiversity Monitoring Program (CBMP) of the Conservation of Arctic Flora and Fauna (CAFF), Arctic Council working group. Salient points about the status and trends of Arctic biodiversity and biodiversity monitoring are organized by taxonomic groups: (1) vegetation, (2) invertebrates, (3) mammals, and (4) birds. This is followed by a discussion about commonalities across the collection of papers, for example, that heterogeneity was a predominant pattern of change particularly when assessing global trends for Arctic terrestrial biodiversity. Finally, the need for a comprehensive, integrated, ecosystem-based monitoring program, coupled with targeted research projects deciphering causal patterns, is discussed.
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| 19. |
- Thompson, PM, et al.
(författare)
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ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries
- 2020
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1, s. 100-
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Tidskriftsartikel (refereegranskat)abstract
- This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA’s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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| 20. |
- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 21. |
- Wierenga, Lara M., et al.
(författare)
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Greater male than female variability in regional brain structure across the lifespan
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 470-499
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Tidskriftsartikel (refereegranskat)abstract
- For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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| 22. |
- Zabel, Florian, et al.
(författare)
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Large potential for crop production adaptation depends on available future varieties
- 2021
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 27:16, s. 3870-3882
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Tidskriftsartikel (refereegranskat)abstract
- Climate change affects global agricultural production and threatens food security. Faster phenological development of crops due to climate warming is one of the main drivers for potential future yield reductions. To counter the effect of faster maturity, adapted varieties would require more heat units to regain the previous growing period length. In this study, we investigate the effects of variety adaptation on global caloric production under four different future climate change scenarios for maize, rice, soybean, and wheat. Thereby, we empirically identify areas that could require new varieties and areas where variety adaptation could be achieved by shifting existing varieties into new regions. The study uses an ensemble of seven global gridded crop models and five CMIP6 climate models. We found that 39% (SSP5-8.5) of global cropland could require new crop varieties to avoid yield loss from climate change by the end of the century. At low levels of warming (SSP1-2.6), 85% of currently cultivated land can draw from existing varieties to shift within an agro-ecological zone for adaptation. The assumptions on available varieties for adaptation have major impacts on the effectiveness of variety adaptation, which could more than half in SSP5-8.5. The results highlight that region-specific breeding efforts are required to allow for a successful adaptation to climate change.
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