| 1. |
- Klaric, Lucija, et al.
(författare)
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Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
- 2021
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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| 2. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 3. |
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A guide to Strategic Partnerships : Structure collaboration between academia and wider society
- 2020
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Samlingsverk (redaktörskap) (populärvet., debatt m.m.)abstract
- To facilitate work on strategic partnerships, 16 higher education institutions in Sweden have produced a guide, within a partnership with funding from Vinnova. The “Strategic Partnership Guide” is a description of and a guide to strategic partnerships. It is formulated from the perspective of a higher education institution. The target group is staff working with collaboration in the area of operational support at Swedish universities and colleges, to provide support in their professional role. The guide may also be useful for vice-chancellors, management teams at higher education institutions, executive boards or academic leaders, to help familiarise themselves with this kind of collaboration. The guide provides an introduction to strategic partnerships and compiles experiences and lessons learned that can facilitate work when getting started with or further developing partnerships.
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| 4. |
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| 5. |
- Eriksson, Daniel, et al.
(författare)
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Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1
- 2018
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 103:1, s. 179-186
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Tidskriftsartikel (refereegranskat)abstract
- Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.
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| 6. |
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| 7. |
- Finnveden, Göran, et al.
(författare)
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Policy instruments towards a sustainable waste management
- 2013
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Ingår i: Sustainability. - Basel : MDPI AG. - 2071-1050. ; 5:3, s. 841-881
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper is to suggest and discuss policy instruments that could lead towards a more sustainable waste management. The paper is based on evaluations from a large scale multi-disciplinary Swedish research program. The evaluations focus on environmental and economic impacts as well as social acceptance. The focus is on the Swedish waste management system but the results should be relevant also for other countries. Through the assessments and lessons learned during the research program we conclude that several policy instruments can be effective and possible to implement. Particularly, we put forward the following policy instruments: “Information”; “Compulsory recycling of recyclable materials”; “Weight-based waste fee in combination with information and developed recycling systems”; “Mandatory labeling of products containing hazardous chemicals”, “Advertisements on request only and other waste minimization measures”; and “Differentiated VAT and subsidies for some services”. Compulsory recycling of recyclable materials is the policy instrument that has the largest potential for decreasing the environmental impacts with the configurations studied here. The effects of the other policy instruments studied may be more limited and they typically need to be implemented in combination in order to have more significant impacts. Furthermore, policy makers need to take into account market and international aspects when implementing new instruments. In the more long term perspective, the above set of policy instruments may also need to be complemented with more transformational policy instruments that can significantly decrease the generation of waste.
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| 8. |
- Finnveden, Göran, et al.
(författare)
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Policy Instruments towards a sustainable waste management
- 2016
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Ingår i: Solid waste management: Policy and planning for a sustainable society. - : Apple Academic Press. - 9781771883740 - 9780429091650 ; , s. 185-246, s. 185-246
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Finnveden, Göran, 1961-, et al.
(författare)
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Regeringen måste satsa på resurseffektivt samhälle
- 2013
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Ingår i: Dagens nyheter. - : AB Dagens nyheter. - 1101-2447. ; :2013-04-01
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Regeringen förbereder en avfallspolitisk proposition. Den kommer förhoppningsvis att klargöra vem som ska ha ansvaret att samla in våra förpackningar. Men fokus borde också ligga på hur vi kan gå mot ett samhälle där resurser används så effektivt som möjligt, skriver forskare på miljöområdet.
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| 10. |
- 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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