| 1. |
- Thorlacius, Guðný Ella, et al.
(författare)
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Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome
- 2021
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 60:2, s. 837-848
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesClinical presentation of primary Sjögren’s syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints.MethodsWe performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls.ResultsWe found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10−62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS.ConclusionTwo subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.
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| 3. |
- Dahlqvist, Johanna, 1979-, et al.
(författare)
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Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
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Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Tidskriftsartikel (refereegranskat)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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| 4. |
- Eklund, Lina, 1982-, et al.
(författare)
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Beyond a dichotomous understanding of online anonymity : bridging the macro and micro level
- 2022
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Ingår i: Sociological Research Online. - : Sage Publications. - 1360-7804. ; 27:2, s. 486-503
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Tidskriftsartikel (refereegranskat)abstract
- Anonymity on the Internet is a contentious issue; by some seen as an important freedom to be protected, while others argue for increased identification to protect groups at risk of exploitation. The debate reflects a dichotomous view of online anonymity; you are, or you are not anonymous. However, anonymity is a complex process played out on different levels and defined by various actors. While empirical studies show this, theoretical synthesis is lacking. This essay provides perspective on anonymity online by comparing two critical cases, online auctions and online gaming, we corroborate results from a 4-year interdisciplinary project with researchers from sociology, economics, and computer and system sciences. We argue that one should talk about anonymities in plural form, as online anonymity is not a state but a relational process. We put forth a conceptual model, which unpacks online anonymity as interdependent macro structures – legal, commercial, and technological – and micro/meso facets – factual, social group, and physical – to be used in future research.
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| 5. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 6. |
- Hesselman, Susanne, 1973-, et al.
(författare)
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Risk of fistula formation and long-term health effects after a benign hysterectomy complicated by organ injury : A population-based register study
- 2018
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:12, s. 1463-1470
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: There is a paucity of data on the impact of organ injury on long-term outcomes after a hysterectomy for benign indications. The aim of this study was to investigate fistula formation and patient-reported long-term health outcomes after organ injury at the time of a hysterectomy.MATERIAL AND METHODS: This was a population-based study of 22 538 women undergoing a hysterectomy between 2000 and 2014 in Sweden. Their medical history, characteristics of their surgery, and patient-reported outcomes were retrieved from Swedish national health and quality registers. Predictors for fistula formation were investigated with logistic regression and are presented as odds ratios with a 95% CI.RESULTS: Fistulas were reported in 7% of women with organ injuries, compared with 0.4% of those without organ injuries (adjusted odds ratio 15.29 [9.81-23.85]). Laparotomy and postoperative infection were associated with postoperative fistulas. Most of the women reported having better health 1 year after the hysterectomy, but 7% of those with organ injuries and 24% of those with fistulas reported deteriorated health, compared with 2% of women without injuries.CONCLUSION: Organ injury at the time of hysterectomy is associated with the development of fistulas involving the female genital tract and increases the proportion of women reporting deteriorated health 1 year after surgery.
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| 7. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 9. |
- Jonsson, Ulf, 1960-, et al.
(författare)
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Inledning
- 2009
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Ingår i: Kritiska tänkanden i religionsvetenskapen. - Nora : Bokförlaget Nya Doxa. - 9789157805430 ; , s. 7-18
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Jonsson, Ulf, 1974-, et al.
(författare)
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Internet-delivered psychological treatment as an add-on to treatment as usual for common mental disorders : A systematic review with meta-analysis of randomized trials
- 2023
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 322, s. 221-234
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Psychological treatments for common mental disorders are increasingly being delivered remotely via the internet. Evidence suggests that internet-delivered cognitive behavioural therapy (iCBT) is superior to waitlist. However, the benefits are unclear of using this treatment modality as an add-on to treatment as usual (TAU) in regular healthcare.METHODS: The literature was systematically searched up to August 2021 for randomized trials of internet-delivered psychological treatments using TAU as the comparator. Eligible participants were diagnosed with depressive, anxiety, obsessive-compulsive, or trauma- and stress-related disorders. Outcomes of interest were symptoms, functioning, quality of life, healthcare utilization, and negative effects. Results were synthesized using random-effects meta-analyses. Quality of evidence was assessed using GRADE.RESULTS: The included studies evaluated iCBT for adults with depression (k = 9), depressive or anxiety disorders (k = 4), and post-traumatic stress disorder (k = 2) and were conducted in primary care or similar settings. For depression, low-certainty evidence suggested beneficial short-term effects on symptoms (g = -0.23; 95 % CI: = -0.37, -0.09), response rate (OR = 2.46; 1.31, 4.64), and remission (OR = 1.70; 1.19, 2.42;). The certainty of evidence was very low for long-term effects, other outcomes, and other disorders.LIMITATIONS: TAU varied across studies and was often insufficiently described.CONCLUSIONS: iCBT as a complement to usual care for adult with depression may result in a small incremental effect, which potentially could be clinically important. Studies are lacking for several common disorders and for children, adolescents, and the elderly. More robust studies of long-term effects are also needed, to better inform clinical decision-making.
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