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Sökning: WFRF:(Scherer S)

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31.
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32.
  • Steinacker, J. M., et al. (författare)
  • Global Alliance for the Promotion of Physical Activity: the Hamburg Declaration
  • 2023
  • Ingår i: Bmj Open Sport & Exercise Medicine. ; 9:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-communicable diseases (NCDs), including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers, are on the rise worldwide and are often associated with a lack of physical activity (PA). Globally, the levels of PA among individuals are below WHO recommendations. A lack of PA can increase morbidity and mortality, worsen the quality of life and increase the economic burden on individuals and society. In response to this trend, numerous organisations came together under one umbrella in Hamburg, Germany, in April 2021 and signed the 'Hamburg Declaration'. This represented an international commitment to take all necessary actions to increase PA and improve the health of individuals to entire communities. Individuals and organisations are working together as the 'Global Alliance for the Promotion of Physical Activity' to drive long-term individual and population-wide behaviour change by collaborating with all stakeholders in the community: active hospitals, physical activity specialists, community services and healthcare providers, all achieving sustainable health goals for their patients/clients. The 'Hamburg Declaration' calls on national and international policymakers to take concrete action to promote daily PA and exercise at a population level and in healthcare settings.
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33.
  • Wilman, H. R., et al. (författare)
  • Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
  • 2019
  • Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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34.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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35.
  • Mullins, Niamh, et al. (författare)
  • Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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36.
  • Ratcliffe, S., et al. (författare)
  • Biodiversity and ecosystem functioning relations in European forests depend on environmental context
  • 2017
  • Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 20:11, s. 1414-1426
  • Tidskriftsartikel (refereegranskat)abstract
    • The importance of biodiversity in supporting ecosystem functioning is generally well accepted. However, most evidence comes from small-scale studies, and scaling-up patterns of biodiversity-ecosystem functioning (B-EF) remains challenging, in part because the importance of environmental factors in shaping B-EF relations is poorly understood. Using a forest research platform in which 26 ecosystem functions were measured along gradients of tree species richness in six regions across Europe, we investigated the extent and the potential drivers of context dependency of B-EF relations. Despite considerable variation in species richness effects across the continent, we found a tendency for stronger B-EF relations in drier climates as well as in areas with longer growing seasons and more functionally diverse tree species. The importance of water availability in driving context dependency suggests that as water limitation increases under climate change, biodiversity may become even more important to support high levels of functioning in European forests.
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37.
  • Docherty, Anna R, et al. (författare)
  • GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
  • 2023
  • Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
  • Tidskriftsartikel (refereegranskat)abstract
    • Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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38.
  • Gohl, K., et al. (författare)
  • Expedition 379 methods
  • 2021
  • Ingår i: Proceedings of the International Ocean Discovery Program. - : International Ocean Discovery Program (IODP). - 2377-3189. ; 379
  • Tidskriftsartikel (refereegranskat)
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39.
  • Gohl, K., et al. (författare)
  • Expedition 379 summary
  • 2021
  • Ingår i: Proceedings of the International Ocean Discovery Program. - : International Ocean Discovery Program (IODP). - 2377-3189. ; 79
  • Tidskriftsartikel (refereegranskat)abstract
    • The Amundsen Sea sector of Antarctica has long been considered the most vulnerable part of the West Antarctic Ice Sheet (WAIS) because of the great water depth at the grounding line, a subglacial bed seafloor deepening toward the interior of the continent, and the absence of substantial ice shelves. Glaciers in this configuration are thought to be susceptible to rapid or runaway retreat. Ice flowing into the Amundsen Sea Embayment is undergoing the most rapid changes of any sector of the Antarctic ice sheets outside the Antarctic Peninsula, including substantial grounding-line retreat over recent decades, as observed from satellite data. Recent models suggest that a threshold leading to the collapse of WAIS in this sector may have been already crossed and that much of the ice sheet could be lost even under relatively moderate greenhouse gas emission scenarios.Drill cores from the Amundsen Sea provide tests of several key questions about controls on ice sheet stability. The cores offer a direct offshore record of glacial history in a sector that is exclusively influenced by ice draining the WAIS, which allows clear comparisons between the WAIS history and low-latitude climate records. Today, relatively warm (modified) Circumpolar Deep Water (CDW) is impinging onto the Amundsen Sea shelf and causing melting under ice shelves and at the grounding line of the WAIS in most places. Reconstructions of past CDW intrusions can assess the ties between warm water upwelling and large-scale changes in past grounding-line positions. Carrying out these reconstructions offshore from the drainage basin that currently has the most substantial negative mass balance of ice anywhere in Antarctica is thus of prime interest to future predictions.The scientific objectives for this expedition are built on hypotheses about WAIS dynamics and related paleoenvironmental and paleoclimatic conditions. The main objectives areTo test the hypothesis that WAIS collapses occurred during the Neogene and Quaternary and, if so, when and under which environmental conditions;To obtain ice-proximal records of ice sheet dynamics in the Amundsen Sea that correlate with global records of ice-volume changes and proxy records for atmospheric and ocean temperatures;To study the stability of a marine-based WAIS margin and how warm deepwater incursions control its position on the shelf;To find evidence for the earliest major grounded WAIS advances onto the middle and outer shelf;To test the hypothesis that the first major WAIS growth was related to the uplift of the Marie Byrd Land dome.International Ocean Discovery Program (IODP) Expedition 379 completed two very successful drill sites on the continental rise of the Amundsen Sea. Site U1532 is located on a large sediment drift, now called the Resolution Drift, and it penetrated to 794 m with 90% recovery. We collected almost-continuous cores from recent age through the Pleistocene and Pliocene and into the upper Miocene. At Site U1533, we drilled 383 m (70% recovery) into the more condensed sequence at the lower flank of the same sediment drift. The cores of both sites contain unique records that will enable study of the cyclicity of ice sheet advance and retreat processes as well as ocean-bottom water circulation and water mass changes. In particular, Site U1532 revealed a sequence of Pliocene sediments with an excellent paleomagnetic record for high-resolution climate change studies of the previously sparsely sampled Pacific sector of the West Antarctic margin.Despite the drilling success at these sites, the overall expedition experienced three unexpected difficulties that affected many of the scientific objectives:The extensive sea ice on the continental shelf prevented us from drilling any of the proposed shelf sites.The drill sites on the continental rise were in the path of numerous icebergs of various sizes that frequently forced us to pause drilling or leave the hole entirely as they approached the ship. The overall downtime caused by approaching icebergs was 50% of our time spent on site.A medical evacuation cut the expedition short by 1 week.Recovery of core on the continental rise at Sites U1532 and U1533 cannot be used to indicate the extent of grounded ice on the shelf or, thus, of its retreat directly. However, the sediments contained in these cores offer a range of clues about past WAIS extent and retreat. At Sites U1532 and U1533, coarse-grained sediments interpreted to be ice-rafted debris (IRD) were identified throughout all recovered time periods. A dominant feature of the cores is recorded by lithofacies cyclicity, which is interpreted to represent relatively warmer periods variably characterized by sediments with higher microfossil abundance, greater bioturbation, and higher IRD concentrations alternating with colder periods characterized by dominantly gray laminated terrigenous muds. Initial comparison of these cycles to published late Quaternary records from the region suggests that the units interpreted to be records of warmer time intervals in the core tie to global interglacial periods and the units interpreted to be deposits of colder periods tie to global glacial periods.Cores from the two drill sites recovered sediments of dominantly terrigenous origin intercalated or mixed with pelagic or hemipelagic deposits. In particular, Site U1533, which is located near a deep-sea channel originating from the continental slope, contains graded silts, sands, and gravels transported downslope from the shelf to the rise. The channel is likely the pathway of these sediments transported by turbidity currents and other gravitational downslope processes. The association of lithologic facies at both sites predominantly reflects the interplay of downslope and contouritic sediment supply with occasional input of more pelagic sediment. Despite the lack of cores from the shelf, our records from the continental rise reveal the timing of glacial advances across the shelf and thus the existence of a continent-wide ice sheet in West Antarctica during longer time periods since at least the late Miocene.Cores from both sites contain abundant coarse-grained sediments and clasts of plutonic origin transported either by downslope processes or by ice rafting. If detailed provenance studies confirm our preliminary assessment that the origin of these samples is from the plutonic bedrock of Marie Byrd Land, their thermochronological record will potentially reveal timing and rates of denudation and erosion linked to crustal uplift. The chronostratigraphy of both sites enables the generation of a seismic sequence stratigraphy for the entire Amundsen Sea continental rise, spanning the area offshore from the Amundsen Sea Embayment westward along the Marie Byrd Land margin to the easternmost Ross Sea through a connecting network of seismic lines.
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40.
  • Ombrello, MJ, et al. (författare)
  • Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications
  • 2017
  • Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:5, s. 906-913
  • Tidskriftsartikel (refereegranskat)abstract
    • Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA.MethodsWe performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes.ResultsThe major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes.ConclusionsThe lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways.
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