1. |
- Saevarsdottir, S., et al.
(författare)
-
Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset
- 2022
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:8
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
|
|
2. |
- Steinthorsdottir, V, et al.
(författare)
-
Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women
- 2020
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 5976-
-
Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.
|
|
3. |
|
|
4. |
|
|
5. |
|
|
6. |
|
|
7. |
|
|
8. |
|
|
9. |
|
|
10. |
|
|
11. |
- Mikaelsdottir, E, et al.
(författare)
-
Genetic variants associated with platelet count are predictive of human disease and physiological markers
- 2021
-
Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1, s. 1132-
-
Tidskriftsartikel (refereegranskat)abstract
- Platelets play an important role in hemostasis and other aspects of vascular biology. We conducted a meta-analysis of platelet count GWAS using data on 536,974 Europeans and identified 577 independent associations. To search for mechanisms through which these variants affect platelets, we applied cis-expression quantitative trait locus, DEPICT and IPA analyses and assessed genetic sharing between platelet count and various traits using polygenic risk scoring. We found genetic sharing between platelet count and counts of other blood cells (except red blood cells), in addition to several other quantitative traits, including markers of cardiovascular, liver and kidney functions, height, and weight. Platelet count polygenic risk score was predictive of myeloproliferative neoplasms, rheumatoid arthritis, ankylosing spondylitis, hypertension, and benign prostate hyperplasia. Taken together, these results advance understanding of diverse aspects of platelet biology and how they affect biological processes in health and disease.
|
|
12. |
|
|
13. |
- Sieberts, SK, et al.
(författare)
-
Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis
- 2016
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12460-
-
Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h2=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.
|
|
14. |
|
|
15. |
|
|
16. |
|
|
17. |
|
|
18. |
|
|
19. |
|
|
20. |
|
|
21. |
|
|
22. |
|
|
23. |
|
|
24. |
- Hambardzumyan, K., et al.
(författare)
-
Association of female sex and positive rheumatoid factor with low serum infliximab and anti-drug antibodies, related to treatment failure in early rheumatoid arthritis : results from the SWEFOT trial population
- 2019
-
Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 48:5, s. 362-366
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Infliximab-treated patients with rheumatoid arthritis (RA) may respond insufficiently due to low serum infliximab (sIFX) levels, caused by anti-drug antibodies (ADAs). However, monitoring of sIFX and ADAs is not routinely implemented, and levels for optimal outcome have not been validated. We searched for predictors for sIFX < 0.2 μg/mL and ADA development in a randomized setting. Methods: In the SWEFOT trial, of 128 patients randomized to methotrexate + IFX therapy, 101 had serum samples at 3, 9, and 21 months that were analysed for sIFX [enzyme-linked immunosorbent assay (ELISA)] and ADAs [ELISA, and precipitation and acid dissociation (PandA) when sIFX > 0.2 μg/mL]. The primary and secondary outcome measures were low disease activity [LDA = 28-joint Disease Activity Score (DAS28) ≤ 3.2] and remission (DAS28 < 2.6). Baseline characteristics were assessed as potential predictors of sIFX < 0.2 μg/mL or ADA positivity, using logistic regression. Results: Categorization of sIFX levels into < 0.2, 0.2–2.9, 3.0–7.0, and > 7.0 μg/mL showed a dose–response association with LDA (30%, 64%, 67%, and 79%, respectively, p = 0.008) and remission (10%, 45%, 39%, and 66%, p = 0.004) at trial cessation (21 months). Female patients had sIFX < 0.2 μg/mL more often than males (35% vs 7%, p = 0.006), with a similar trend for rheumatoid factor (RF)-positive vs RF-negative patients (34% vs 16%, p = 0.059). ADA positivity showed similar patterns, also after adjustment for potential confounders (female sex: p = 0.050; RF positivity: p = 0.067). PandA captured four highly ADA-reactive patients with sIFX > 0.2 μg/mL, of whom three were ADA positive at other time-points, all with high DAS28 at follow-up. Conclusion: In early RA patients receiving IFX as a second-line agent, sIFX < 0.2 μg/mL and ADA development were associated with treatment failure and were more common in females, with a similar trend for RF positivity. Our findings support the use of therapeutic drug monitoring, and PandA in ADA-negative non-responders. Trial registration: SWEFOT NCT00764725 (https://clinicaltrials.gov/ct2/show/NCT00764725).
|
|
25. |
|
|
26. |
|
|
27. |
|
|
28. |
|
|
29. |
|
|
30. |
|
|
31. |
- Hedenstierna, L, et al.
(författare)
-
THE ASSOCIATION BETWEEN SOCIAL STRESSORS AND DISEASE REMISSION AMONG MEN AND WOMEN WITH EARLY RHEUMATOID ARTHRITIS
- 2021
-
Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 474-475
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The role of psychosocial conditions on the disease course of rheumatoid arthritis (RA) is getting increased attention. In our previous study, low social support and low decision latitude at work were associated with known modifiable risk factors for RA disease development, such as smoking and low educational level (1). Further, smoking and low educational level have previously been shown to be associated with worse RA disease outcome (2-4). Whether psychosocial characteristics are related to RA disease outcome needs further investigation.Objectives:To investigate the relationship between two psychosocial characteristics: low social support and low decision latitude at work, and achievement of remission in patients with RA.Methods:At inclusion in the Swedish EIRA study, incident RA cases (N=3724) and controls (N=5937), matched for age, sex and residential area, responded to a questionnaire including questions on social support and decision latitude at work. The answers were recoded into separate scores and the distribution of the scores among controls were used to define the exposures. Low social support and low decision latitude at work, respectively, among patients, were set as the level corresponding to the lowest quartile among controls, and were compared with scores corresponding to the remaining three quartiles.The outcome, disease activity score 28-joint count (DAS28) remission, defined as DAS28<2.6, was captured through linkage with the Swedish Rheumatology Quality Register (SRQ) with data available from diagnosis for 2693 out of 3700 cases for social support and for 847 out of 1248 cases for decision latitude at work.Logistic regression was used to evaluate the association between low social support or low decision latitude at work, respectively, and the chance of remission at the time-points 3 months, 12 months and 60 months after inclusion. All results were adjusted for age, sex and residential area and the fully adjusted models were also adjusted for smoking, obesity, physical activity and educational level.Results:Low social support (n=655) was associated with a reduced chance for remission at all three time points in the model adjusted for age, sex and residential area; OR 3 months 0.77 (95% CI 0.61-0.97), OR 12 months 0.78 (95% CI 0.64-0.95) OR 60 months 0.77 (95% CI 0.59-0.99). This association was diminished after further adjustment. After stratifying for sex, this association was enhanced in women but inverse among men (Figure 1).No association between low decision latitude at work (n=166) and chance for remission was observed neither in the analyses stratified for matching variables, nor in the full model. This result was only marginally changed after stratifying for sex (Figure 1).Conclusion:Low social support was associated with lower chance of remission in early RA, but the association was not independent of other risk factors for worse outcome (smoking, physical activity, obesity and low educational level).The interrelationship between social stressors and previously known risk factors for worse outcome highlights the importance of supportive actions at many levels to increase the possibility for the individual to make healthy decisions.References:[1]Hedenstierna. et al. Scand J Rheumatol. 2021:1-5.[2]Saevarsdottir, et al. Ann Rheum Dis. 2011;70(3):469-75.[3]Saevarsdottir, et al. Arthritis Rheum. 2011;63(1):26-36.[4]Jiang, et al. Arthritis Res Ther. 2015;17:317.Figure 1.Odds ratios for assiciation between social stressors and DAS 28 remissionAcknowledgements:We want to thank all the participants of the EIRA study and the clinical collaborators for their valuable contribution. We also want to thank the staff for their dedicated work with the data collection.Disclosure of Interests:None declared
|
|
32. |
|
|
33. |
|
|
34. |
- Karlsson, M-l, et al.
(författare)
-
Evaluation of an individually tailored smoking-cessation intervention for patients with rheumatoid arthritis in an outpatient clinic
- 2023
-
Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis. - 0300-9742 .- 1502-7732. ; 52:6, s. 591-600
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to evaluate an individually tailored smoking-cessation intervention delivered in rheumatology care and compare the characteristics of patients who quit smoking with those who did not.Method: This was an open single-group prospective intervention study over 24 months, with assessments at baseline and at 6, 12, 18, and 24 months. Current smokers with rheumatoid arthritis (RA) were invited to a smoking-cessation programme including behavioural change support, with or without pharmacotherapy. Data on disease activity, medical treatment, and patient-reported outcomes were retrieved from the Swedish Rheumatology Quality Register. The primary outcome was the proportion of patients at month 24 who reported having quit smoking with self-reported 7 day smoking abstinence.Results: In total, 99 patients participated in the study. Median age was 58 years (interquartile range 50-64); 69% were female and 88% rheumatoid factor and/or anti-cyclic citrullinated peptide positive. At 24 months, 21% of the patients had quit smoking. At 6, 12, and 18 months, 12%, 12%, and 14% of patients, respectively, had quit smoking. For patients still smoking at 24 months, the median number of cigarettes per day was significantly reduced from 12 to 6 (p <= 0.001). Among patients who had quit smoking at 24 months, a smaller proportion reported anxiety at baseline compared to those still smoking (28% vs 58%, p = 0.02).Conclusion: A smoking-cessation intervention including behavioural change support with or without pharmacotherapy can be helpful for a substantial number of RA patients. Anxiety is associated with lower smoking-cessation success rates.
|
|
35. |
- Karlsson, ML, et al.
(författare)
-
THE EFFECT OF A PERSON-CENTERED SMOKING CESSATION PROGRAM IN RHEUMATOID ARTHRITIS PATIENTS IN A RHEUMATOLOGY OUTPATIENT CLINIC SETTING - RESULTS OF AN INTERVENTIONAL FEASIBILITY STUDY
- 2021
-
Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 93-94
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Smoking is associated with worse treatment response1 and higher mortality2 in rheumatoid arthritis (RA).Objectives:To assess the effect of a smoking cessation intervention in a rheumatology setting.Methods:We designed a smoking cessation interventional feasibility study. RA patients who were active smokers were asked to participate. A nurse-delivered program consisting of behavioural changes techniques and voluntary pharmacotherapy was executed. The intervention was at baseline and at several time points during a 24 month period, based on the individual patient’s needs. Smoking status was collected at baseline, 6, 12, 18 and 24 months. Smoking cessation was verified by 7-days abstinence and carbon monoxide in expiratory air. The main outcome was the proportion of patients who quit smoking (QS) at 24 months.Results:A total of 99 patients were included in the study between 2011-2020. Median (IQR) age of patients was 58 (50 - 64), 69 % were female and 82% were RF and/or ACPA positive. 59% of patients had a newly diagnosed RA, (included from the early RA-track), with a median (IQR) symptom duration of 5 (2-9,5) months. Patients with established RA 41% (included from regular rheumatology department) had a median disease duration of 4 (2-8) years. After 24 months 21% quit smoking (QS) (Table 1). At months 6, 12, 18 and 24 the proportion of QS patients was 12, 13, 15 and 21, respectively. The proportion of QS patients at month 12 and continued being in the QS group throughout the study period was 10%. In the subgroup of patients who continued smoking (CS) the median number of cigarettes per day was significantly reduced at all follow-up time points (Table 1). No significant differences were observed at baseline between CS at 24 months and QS, apart from the proportion of patients who reported anxiety (extracted from EQ-5D and defined as absent or present), which was significantly fewer in the QS group (Table). In the QS group at month 24, the proportion of females was numerically lower compared to CS (52% vs. 73%, p=0.07).Table 1.Baseline demographical, clinical characteristics and number of cigarettes at specific time-points for patients who were non-smokers (QS) and smokers (CS) at month 24.QSN=21 (21%)CSN=78 (79%)Difference between QS and CS(p-value)Age*(median, IQR)60 (53-62)57 (50-64)0.94Symptom duration in early RA patients (months) (median, IQR)6 (2-12)4.5 (2-8.5)0.49Disease duration of patients with established RA (years) (median, IQR)8 (3.5-16.5)3 (2-6)0.12% females52730.07% RF and/or ACPA positive85810.70DAS28* (median, IQR)4.24 (3.13-5.72)4.11 (2.88-5.36)0.69HAQ* (median, IQR)0.75 (0.25 -1.38)0.88 (0.38-1.25)0.74VAS pain* (median, IQR)46.0 (11-60)34.5 (12-70)0.90% of patients with reported anxiety* (part of EQ5D)28580.02Smoking duration (years)(median, IQR)40 (30-50)40 (34-49)0.92Median number of cigarettes per day-at baseline10 (7-15)12 (10-20)0.22-at 6 months0 (0-3)6 (3-10)0.006-at 12 months0 (0-5)6 (3-10)0.0003-at 18 months0 (0-0)6 (2-10)0.00-at 24 months0 (0-0)6 (3-10)0.00*=measured at baselineConclusion:Smoking cessation intervention in a rheumatology clinic setting may facilitate reduced smoking or complete cessation in patients with RA. Patient who did not report anxiety were more likely to quit smoking.References:[1]Saevarsdottir, S., et al (2011). Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: observations from the Epidemiological Investigation of Rheumatoid Arthritis and the Swedish Rheumatology Register cohorts. Arthritis Rheum, 63(1), 26-36.[2]Joseph, R´., et al (2016) Smoking-Related Mortality in Patients With Early Rheumatoid Arthritis: A Retrospective Cohort Study Using the Clinical Practice Research Datalink Arthritis Care Res (Hoboken) 68 (11) 1598-1606Acknowledgements:This study was partly funded by grants from Swedish Reumatism Association.Disclosure of Interests:Marie-Louise Karlsson Speakers bureau: MLK has recivied fee form Novartis Sverige AB, Grant/research support from: MLK had recivied finical grants from Novartis Sverige. Abbvie has fincial support brochure wich was used in the study, Katarina Hertzberg-Nyquist: None declared, Saedis Saevarsdottir Employee of: S is a part-time employee of deCODE genetics Inc., unrelated to this work., Ingrid E. Lundberg Consultant of: I Lundberg har recieved consulting fees from Corbus Pharmaceutical, EMD Serono Research & Development Institute, Octapharma AG, Orphazyme, Janssen, Kezar Life Sciences Inc., Ingrid Demmelmaie: None declared, Susanne Pettersson: None declared, Katerina Chatzidionysiou Consultant of: KC has received consultancy fees from Eli Lilly, AbbVie and Pfizer.
|
|
36. |
- Lourido, L., et al.
(författare)
-
Circulating centromere protein F autoantibodies for predicting clinical response to infliximab in rheumatoid arthritis
- 2020
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 79, s. 1399-1399
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- One third of patients with rheumatoid arthritis (RA) respond poorly to TNF inhibitors and related studies are inconsistent in predictive biomarkers. The identification of biomarkers that predict the treatment response prior to drug exposure is a current priority on the RA field. ACPA and RF are ubiquitously tested in RA patients, but other autoantibodies exist and may provide additional information on RA treatment response.Objectives:This study aimed to identify circulating autoantibodies for predicting response to infliximab (IFX) in RA.Methods:We profiled the autoantibody repertoire of baseline sera from 155 biologic naïve RA patients treated with IFX. The sera were provided by three independent clinical sources and distributed in one exploratory cohort (N=20) collected from Hospital Clínico Universitario of Santiago de Compostela (Spain), one replication cohort (N=61) collected from Hospital Universitario de A Coruña (Spain) and samples from the Swedish Farmacotherapy (SWEFOT) trial (Sweden) (N=74) for clinical validation. The presence of autoantibodies and their levels in serum were analysed in association with EULAR clinical response at 6 months follow-up: good response (GR, N=56), moderate (MR, N=55) and non-response (NR, N=44). A suspension bead array platform built on protein fragments within Human Protein Atlas and selected from an initial untargeted screening using an array containing 42000 antigens was employed to identify the IgG and IgA autoantibodies on the exploratory cohort. A replication and validation phases were carried out on the other two serum sample cohorts. Meta-analysis and Receiver Operating Curves were performed in order to assess the clinical relevance of the findings observed.Results:Meta-analysis revealed that the levels in serum of IgG autoantibodies against Centromere protein F (CENPF) are significantly increased in responders (good responders and moderate responders; N=111) to IFX compared to non-responders (N=44) (P=0.018). CENP-F is a proliferation-associated and cell cycle-dependent centromere autoantigen that might be involved in the increased or abnormal cell proliferation that occurs during RA process. The combination of the anti-CENPF antibodies with clinical variables (age, sex, DAS28-ESR) resulted in the best model to discriminate the patients that will respond to IFX, showing an AUC of 0.756 (95% CI [0.639-0.874], P=0.001).Conclusion:High serum levels of IgG anti-CENPF antibodies might be potentially useful to identify RA patients more likely to benefit from IFXDisclosure of Interests:Lucía Lourido: None declared, Cristina Ruiz-Romero: None declared, flor picchi: None declared, Naomi Diz-Rosales: None declared, Sergio Vilaboa-Galán: None declared, Carlos Fernández-López: None declared, Jose Antonio Pinto Tasende: None declared, Eva Perez-Pampin: None declared, Cristina Regueiro Expósito: None declared, ANTONIO MERA VARELA: None declared, Antonio Gonzalez: None declared, Karen Hambardzumyan: None declared, Saedis Saevarsdottir Employee of: Part-time at deCODE Genetics/Amgen Inc, working on genetic research unrelated to this project, Peter Nilsson: None declared, Francisco J. Blanco Grant/research support from: Sanofi-Aventis, Lilly, Bristol MS, Amgen, Pfizer, Abbvie, TRB Chemedica International, Glaxo SmithKline, Archigen Biotech Limited, Novartis, Nichi-iko pharmaceutical Co, Genentech, Jannsen Research & Development, UCB Biopharma, Centrexion Theurapeutics, Celgene, Roche, Regeneron Pharmaceuticals Inc, Biohope, Corbus Pharmaceutical, Tedec Meiji Pharma, Kiniksa Pharmaceuticals, Ltd, Gilead Sciences Inc, Consultant of: Lilly, Bristol MS, Pfizer
|
|
37. |
|
|
38. |
|
|
39. |
|
|
40. |
|
|
41. |
- Saevarsdottir, KS, et al.
(författare)
-
Illness severity and risk of mental morbidities among patients recovering from COVID-19: a cross-sectional study in the Icelandic population
- 2021
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:7, s. e049967-
-
Tidskriftsartikel (refereegranskat)abstract
- To test if patients recovering from COVID-19 are at increased risk of mental morbidities and to what extent such risk is exacerbated by illness severity.DesignPopulation-based cross-sectional study.SettingIceland.ParticipantsA total of 22 861 individuals were recruited through invitations to existing nationwide cohorts and a social media campaign from 24 April to 22 July 2020, of which 373 were patients recovering from COVID-19.Main outcome measuresSymptoms of depression (Patient Health Questionnaire), anxiety (General Anxiety Disorder Scale) and posttraumatic stress disorder (PTSD; modified Primary Care PTSD Screen for DSM-5) above screening thresholds. Adjusting for multiple covariates and comorbidities, multivariable Poisson regression was used to assess the association between COVID-19 severity and mental morbidities.ResultsCompared with individuals without a diagnosis of COVID-19, patients recovering from COVID-19 had increased risk of depression (22.1% vs 16.2%; adjusted relative risk (aRR) 1.48, 95% CI 1.20 to 1.82) and PTSD (19.5% vs 15.6%; aRR 1.38, 95% CI 1.09 to 1.75) but not anxiety (13.1% vs 11.3%; aRR 1.24, 95% CI 0.93 to 1.64). Elevated relative risks were limited to patients recovering from COVID-19 that were 40 years or older and were particularly high among individuals with university education. Among patients recovering from COVID-19, symptoms of depression were particularly common among those in the highest, compared with the lowest tertile of influenza-like symptom burden (47.1% vs 5.8%; aRR 6.42, 95% CI 2.77 to 14.87), among patients confined to bed for 7 days or longer compared with those never confined to bed (33.3% vs 10.9%; aRR 3.67, 95% CI 1.97 to 6.86) and among patients hospitalised for COVID-19 compared with those never admitted to hospital (48.1% vs 19.9%; aRR 2.72, 95% CI 1.67 to 4.44).ConclusionsSevere disease course is associated with increased risk of depression and PTSD among patients recovering from COVID-19.
|
|
42. |
|
|
43. |
|
|
44. |
|
|
45. |
|
|
46. |
|
|
47. |
|
|
48. |
|
|
49. |
- Skuladottir, AT, et al.
(författare)
-
A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1598-
-
Tidskriftsartikel (refereegranskat)abstract
- Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and has a largely unknown underlying biology. In a genome-wide association study of CTS (48,843 cases and 1,190,837 controls), we found 53 sequence variants at 50 loci associated with the syndrome. The most significant association is with a missense variant (p.Glu366Lys) in SERPINA1 that protects against CTS (P = 2.9 × 10−24, OR = 0.76). Through various functional analyses, we conclude that at least 22 genes mediate CTS risk and highlight the role of 19 CTS variants in the biology of the extracellular matrix. We show that the genetic component to the risk is higher in bilateral/recurrent/persistent cases than nonrecurrent/nonpersistent cases. Anthropometric traits including height and BMI are genetically correlated with CTS, in addition to early hormonal-replacement therapy, osteoarthritis, and restlessness. Our findings suggest that the components of the extracellular matrix play a key role in the pathogenesis of CTS.
|
|
50. |
- Skuladottir, AT, et al.
(författare)
-
A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo
- 2021
-
Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1, s. 1148-
-
Tidskriftsartikel (refereegranskat)abstract
- Vertigo is the leading symptom of vestibular disorders and a major risk factor for falls. In a genome-wide association study of vertigo (Ncases = 48,072, Ncontrols = 894,541), we uncovered an association with six common sequence variants in individuals of European ancestry, including missense variants in ZNF91, OTOG, OTOGL, and TECTA, and a cis-eQTL for ARMC9. The association of variants in ZNF91, OTOGL, and OTOP1 was driven by an association with benign paroxysmal positional vertigo. Using previous reports of sequence variants associating with age-related hearing impairment and motion sickness, we found eight additional variants that associate with vertigo. Although disorders of the auditory and the vestibular system may co-occur, none of the six genome-wide significant vertigo variants were associated with hearing loss and only one was associated with age-related hearing impairment. Our results uncovered sequence variants associating with vertigo in a genome-wide association study and implicated genes with known roles in inner ear development, maintenance, and disease.
|
|