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- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 5. |
- 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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| 6. |
- Hutchinson, Louise A., et al.
(författare)
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Using ecological and field survey data to establish a national list of the wild bee pollinators of crops
- 2021
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Ingår i: Agriculture, Ecosystems and Environment. - : Elsevier BV. - 0167-8809 .- 1873-2305. ; 315
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Tidskriftsartikel (refereegranskat)abstract
- The importance of wild bees for crop pollination is well established, but less is known about which species contribute to service delivery to inform agricultural management, monitoring and conservation. Using sites in Great Britain as a case study, we use a novel qualitative approach combining ecological information and field survey data to establish a national list of crop pollinating bees for four economically important crops (apple, field bean, oilseed rape and strawberry). A traits data base was used to establish potential pollinators, and combined with field data to identify both dominant crop flower visiting bee species and other species that could be important crop pollinators, but which are not presently sampled in large numbers on crops flowers. Whilst we found evidence that a small number of common, generalist species make a disproportionate contribution to flower visits, many more species were identified as potential pollinators, including rare and specialist species. Furthermore, we found evidence of substantial variation in the bee communities of different crops. Establishing a national list of crop pollinators is important for practitioners and policy makers, allowing targeted management approaches for improved ecosystem services, conservation and species monitoring. Data can be used to make recommendations about how pollinator diversity could be promoted in agricultural landscapes. Our results suggest agri-environment schemes need to support a higher diversity of species than at present, notably of solitary bees. Management would also benefit from targeting specific species to enhance crop pollination services to particular crops. Whilst our study is focused upon Great Britain, our methodology can easily be applied to other countries, crops and groups of pollinating insects.
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| 7. |
- Senapathi, Deepa, et al.
(författare)
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Wild insect diversity increases inter-annual stability in global crop pollinator communities
- 2021
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Ingår i: Royal Society of London. Proceedings B. Biological Sciences. - : The Royal Society. - 1471-2954 .- 0962-8452. ; 288:1947
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Tidskriftsartikel (refereegranskat)abstract
- While an increasing number of studies indicate that the range, diversity and abundance of many wild pollinators has declined, the global area of pollinator-dependent crops has significantly increased over the last few decades. Crop pollination studies to date have mainly focused on either identifying different guilds pollinating various crops, or on factors driving spatial changes and turnover observed in these communities. The mechanisms driving temporal stability for ecosystem functioning and services, however, remain poorly understood. Our study quantifies temporal variability observed in crop pollinators in 21 different crops across multiple years at a global scale. Using data from 43 studies from six continents, we show that (i) higher pollinator diversity confers greater inter-annual stability in pollinator communities, (ii) temporal variation observed in pollinator abundance is primarily driven by the three-most dominant species, and (iii) crops in tropical regions demonstrate higher inter-annual variability in pollinator species richness than crops in temperate regions. We highlight the importance of recognizing wild pollinator diversity in agricultural landscapes to stabilize pollinator persistence across years to protect both biodiversity and crop pollination services. Short-term agricultural management practices aimed at dominant species for stabilizing pollination services need to be considered alongside longer term conservation goals focussed on maintaining and facilitating biodiversity to confer ecological stability.
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| 8. |
- van Laarhoven, Cjhcm, et al.
(författare)
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Delayed Development of Aneurysmal Dilatations in Patients with Extracranial Carotid Artery Dissections
- 2022
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884. ; 64:6, s. 595-601
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Dissection of the carotid artery (CaAD) may result in aneurysm formation. The present study was undertaken to evaluate the time of onset of post-dissection extracranial carotid artery aneurysms (ECAA) following CaAD, and to analyse independent risk factors for the development of these aneurysms. Methods: From four European stroke centres, 360 patients with extracranial CaAD were included. The time between the estimated dissection onset and aneurysm formation was analysed, and the clinical risk factors increasing the probability of aneurysm were assessed. Results: The median duration of follow up was 5.2 months (range 0 - 24 months). A total of 75 post-dissection ECAAs were identified in 70 patients (19.4%, 95% confidence interval [CI] 15.7 - 23.8). In 52 of 70 (74%) patients, the ECAA was diagnosed at the initial clinical work up of CaAD diagnosis, with the median estimated time of dissection onset to ECAA diagnosis being six days (interquartile range [IQR] 0 - 25). In the remaining 18 (26%) patients who had normal carotid arteries at the initial imaging, the aneurysm diagnosis was made a median of 6.2 months (189 days) from the original imaging (IQR 128 - 198). A Cox proportional hazards model showed that both multiple artery dissections (hazard ratio [HR] 2.58, 95% CI 1.54 - 4.33) and arterial tortuosity (HR 1.79, 95% CI 1.08 - 2.95) were associated with presence of ipsilateral ECAA. Conclusion: This post hoc cohort analysis showed substantially delayed development of ipsilateral ECAA in patients with CaAD, months after baseline. Multiple dissections and arterial tortuosity are associated with the presence of ECAA and can be used in future prediction models of ECAA development in patients with CaAD.
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| 9. |
- Mei, Zulin, et al.
(författare)
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Distance decay effects predominantly shape spider but not carabid community composition in crop fields in north-western Europe
- 2024
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Ingår i: Basic and Applied Ecology. - 1439-1791. ; 79, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Agricultural intensification and expansion are regarded as main drivers of biodiversity loss. This conclusion is mainly based on observed declines of local diversity (α-diversity), while effects on community composition homogenization (decrease of β-diversity) at a larger spatial scale are less well understood. Carabid beetles and spiders represent two widespread guilds and are important predators of pest species. Here we surveyed carabid beetles and spiders in 66 winter wheat fields in four northwestern European countries (Germany, the Netherlands, Sweden and UK) and analyzed how their community composition was related to geographic distance (separation distance between any pairwise fields) and three environmental variables: crop yield (proxy for land-use intensity), percentage cropland (proxy for landscape complexity) and soil organic carbon content (proxy for local soil conditions). We further analyzed whether the relationship between carabid beetle and spider community composition and geographic distance was influenced by environmental variables. We found that, 55 % and 75 % of all observed carabid and spider individuals, respectively, belonged to species that occurred in all four countries. However, individuals of species that were unique to a particular country only accounted for 3 % of all collected individuals for both taxa. Furthermore, we found a negative relationship between distance and similarity of spider communities but not for carabid beetle communities. None of the environmental variables were related to similarity of carabid beetle and spider communities, nor moderated the effects of distance. Our study indicates that across a great part of the European continent, arthropod communities (especially carabid beetles) in agricultural landscapes are composed of very similar species that are robust to current variations in environment and land-use.
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| 10. |
- Mei, Zulin, et al.
(författare)
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Inconsistent responses of carabid beetles and spiders to land-use intensity and landscape complexity in north-western Europe
- 2023
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Ingår i: Biological Conservation. - 0006-3207 .- 1873-2917. ; 283
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Tidskriftsartikel (refereegranskat)abstract
- Reconciling biodiversity conservation with agricultural production requires a better understanding of how key ecosystem service providing species respond to agricultural intensification. Carabid beetles and spiders represent two widespread guilds providing biocontrol services. Here we surveyed carabid beetles and spiders in 66 winter wheat fields in four northwestern European countries and analyzed how the activity density and diversity of carabid beetles and spiders were related to crop yield (proxy for land-use intensity), percentage cropland (proxy for landscape complexity) and soil organic carbon content, and whether these patterns differed between dominant and non-dominant species. <17 % of carabid or spider species were classified as dominant, which accounted for >90 % of individuals respectively. We found that carabids and spiders were generally related to different aspects of agricultural intensification. Carabid species richness was positively related with crop yield and evenness was negatively related to crop cover. The activity density of non-dominant carabids was positively related with soil organic carbon content. Meanwhile, spider species richness and non-dominant spider species richness and activity density were all negatively related to percentage cropland. Our results show that practices targeted to enhance one functionally important guild may not promote another key guild, which helps explain why conservation measures to enhance natural enemies generally do not ultimately enhance pest regulation. Dominant and non-dominant species of both guilds showed mostly similar responses suggesting that management practices to enhance service provisioning by a certain guild can also enhance the overall diversity of that particular guild.
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