| 1. |
- Mitchell, Jonathan S., et al.
(författare)
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Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P = 1.31 x 10(-8)), 6q21 (rs9372120, P = 9.09 x 10(-15)), 7q36.1 (rs7781265, P = 9.71 x 10(-9)), 8q24.21 (rs1948915, P = 4.20 x 10(-11)), 9p21.3 (rs2811710, P = 1.72 x 10(-13)), 10p12.1 (rs2790457, P = 1.77 x 10(-8)), 16q23.1 (rs7193541, P = 5.00 x 10(-12)) and 20q13.13 (rs6066835, P = 1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
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| 2. |
- Roseman, C., et al.
(författare)
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Persistent pain and its predictors after starting anti-tumour necrosis factor therapy in psoriatic arthritis : what is the role of inflammation control?
- 2024
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Ingår i: Scandinavian Journal of Rheumatology. - 0300-9742 .- 1502-7732. ; 53:2, s. 94-103
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Tidskriftsartikel (refereegranskat)abstract
- Objective: While considerable focus has been placed on pain due to inflammation in psoriatic arthritis (PsA), less is reported on pain despite inflammation control. Here, we aimed to investigate the occurrence/predictors of persistent pain, including non-inflammatory components, after starting anti-tumour necrosis factor (anti-TNF) therapy. Method: Bionaïve PsA patients starting a first anti-TNF therapy 2004–2010 were identified (South Swedish Arthritis Treatment Group register; N = 351). Outcomes included unacceptable pain [visual analogue scale (VAS) pain > 40 mm], and unacceptable pain despite inflammation control (refractory pain; VAS pain > 40 mm + C-reactive protein < 10 mg/L + ≤ 1 swollen joint of 28), assessed at 0, 3, 6, and 12 months. Baseline predictors were estimated by logistic regression. Results: Upon starting anti-TNF therapy, 85% of patients reported unacceptable pain, falling to 43% at 3 months and then remaining stable. After 12 months, refractory pain constituted 63% of all unacceptable pain. Higher baseline VAS pain/global, worse physical function and lower health-related quality-of-life were associated with a higher risk of unacceptable/refractory pain at 12 months. More swollen joints and higher evaluator’s global assessment were associated with a lower risk of 12-month refractory pain. Conclusions: A substantial proportion of PsA patients reported unacceptable pain throughout the first anti-TNF treatment year. At 12 months, refractory pain constituted about two-thirds of this remaining pain load. More objective signs of inflammation at anti-TNF initiation were associated with less future refractory pain. This highlights insufficient effect of biologics in patients with inflammation-independent pain, warranting alternative treatments.
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| 3. |
- Ajore, Ram, et al.
(författare)
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Deletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert with TP53 mutations
- 2017
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 9:4, s. 498-507
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Tidskriftsartikel (refereegranskat)abstract
- Heterozygous inactivating mutations in ribosomal protein genes (RPGs) are associated with hematopoietic and developmental abnormalities, activation of p53, and altered risk of cancer in humans and model organisms. Here we performed a large-scale analysis of cancer genome data to examine the frequency and selective pressure of RPG lesions across human cancers. We found that hemizygous RPG deletions are common, occurring in about 43% of 10,744 cancer specimens and cell lines. Consistent with p53-dependent negative selection, such lesions are underrepresented in TP53-intact tumors (P ≪ 10−10), and shRNA-mediated knockdown of RPGs activated p53 in TP53-wild-type cells. In contrast, we did not see negative selection of RPG deletions in TP53-mutant tumors. RPGs are conserved with respect to homozygous deletions, and shRNA screening data from 174 cell lines demonstrate that further suppression of hemizygously deleted RPGs inhibits cell growth. Our results establish RPG haploinsufficiency as a strikingly common vulnerability of human cancers that associates with TP53 mutations and could be targetable therapeutically.
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| 4. |
- Bondesson, E., et al.
(författare)
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Comorbidity between pain and mental illness - Evidence of a bidirectional relationship
- 2018
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Ingår i: European Journal of Pain. - : Wiley. - 1090-3801. ; 22:7, s. 1304-1311
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pain from various locations in the body and mental illness are common and the comorbidity between the two is well-known although the temporal relationship remains to be determined. Our aim was to follow patients over time to study if pain (here dorsalgia/abdominal pain) or fibromyalgia lead to an increased risk of developing mental illness (here depression/anxiety) and/or the reverse, that is whether patients with mental illness have an increased risk to develop pain or fibromyalgia, compared to the rest of the population. Methods: This prospective cohort study used the Skåne Healthcare Register, covering all care in the region of Skåne, southern Sweden (population ~1.3 million). The cohort included healthcare consultations in primary care, outpatient specialized care and inpatient care between 2007 and 2016 for all patients without prior registered diagnosis of mental illness or pain, aged 18 or older (n = 504,365). Results: The incidence rate ratio (IRR) for developing mental illness after pain was 2.18 (95% CI = 2.14-2.22) compared to without pain. IRR for developing pain after mental illness was 2.02 (95% CI = 1.98-2.06) compared to without mental illness. Corresponding IRR for developing mental illness after fibromyalgia was 4.05 (95% CI = 3.58-4.59) and for developing fibromyalgia after mental illness 5.54 (95% CI = 4.99-6.16). Conclusions: This study shows a bidirectional influence of similar magnitude of pain and mental illness, respectively. In monitoring patients with pain or mental illness, a focus on both conditions is thus important to develop appropriate, targeted interventions and may increase the likelihood of improved outcomes. Significance: We followed a population-based cohort over a period of 10 years, including incident cases of both exposure and outcome and found a bidirectional relationship between pain and mental illness. Clinicians need to pay attention on both conditions, in patients seeking care due to mental illness or pain.
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| 5. |
- Bondesson, E, et al.
(författare)
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Consultation prevalence among children, adolescents and young adults with pain conditions : A description of age- And gender differences
- 2020
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Ingår i: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 24:3, s. 649-658
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pain is a common complaint presented in healthcare, but most epidemiological pain research has focused either on single pain conditions or on the adult population. The aim of this study was to investigate the 2017 consultation prevalence of a wide range of pain conditions in the general population of young people.METHODS: We used the Skåne Healthcare Register, covering prospectively collected data on all healthcare delivered (primary and secondary care) to the population in the region of Skåne, southern Sweden (population 2017 n = 1,344,689). For individuals aged 1-24 in 2017 (n = 373,178), we calculated the consultation prevalence, stratified by sex and age, and the standardised morbidity ratio (SMR) to assess overall healthcare consultation.RESULTS: A total of 58,981 (15.8%) individuals consulted at least once for any of the predefined pain conditions. Of these, 13.5% (n = 7,996) consulted four or more times for pain. Abdominal pain, joint pain/myalgia, headache and back/neck pain were the most common complaints. Overall, females had higher consultation prevalence than males: 17.6% versus 14.1% (p < .0001). SMR was 1.82 (95% CI = 1.74-1.87) for females with pain and 1.51 (95% CI = 1.42-1.56) for males with pain. Consultation prevalence increased with age, but this pattern varied between sex and pain condition.CONCLUSIONS: Among individuals under the age of 25, a significant proportion consult for pain already in early ages, and they also have high healthcare consultation rates for conditions other than pain. The even higher consultation rates among young females need additional attention, both in the clinic and in research.
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| 6. |
- Christophersen, Mikael K., et al.
(författare)
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SMIM1 variants rs1175550 and rs143702418 independently modulate Vel blood group antigen expression
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The Vel blood group antigen is expressed on the red blood cells of most individuals. Recently, we described that homozygosity for inactivating mutations in SMIM1 defines the rare Vel-negative phenotype. Still, Vel-positive individuals show great variability in Vel antigen expression, creating a risk for Vel blood typing errors and transfusion reactions. We fine-mapped the regulatory region located in SMIM1 intron 2 in Swedish blood donors, and observed a strong correlation between expression and rs1175550 as well as with a previously unreported tri-nucleotide insertion (rs143702418; C > CGCA). While the two variants are tightly linked in Caucasians, we separated their effects in African Americans, and found that rs1175550G and to a lesser extent rs143702418C independently increase SMIM1 and Vel antigen expression. Gel shift and luciferase assays indicate that both variants are transcriptionally active, and we identified binding of the transcription factor TAL1 as a potential mediator of the increased expression associated with rs1175550G. Our results provide insight into the regulatory logic of Vel antigen expression, and extend the set of markers for genetic Vel blood group typing.
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| 7. |
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| 8. |
- Kander, Thomas, et al.
(författare)
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ABO and RhD blood group are not associated with mortality and morbidity in critically ill patients; a multicentre observational study of 29 512 patients
- 2022
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Ingår i: BMC Anesthesiol. - : Springer Science and Business Media LLC. - 1471-2253. ; 22:1, s. 91-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The ABO and RhD blood group represent antigens on the surface of erythrocytes. The ABO blood group antigens are also present on multiple other cells. Interestingly, previous studies have demonstrated associations between the blood group and many types of disease. The present study aimed to identifying associations between the ABO blood group, the RhD blood group, and morbidity and mortality in a mixed cohort and in six pre-defined subgroups of critically ill patients. METHODS: Adult patients admitted to any of the five intensive care units (ICUs) in the Scania Region, Sweden, between February 2007 and April 2021 were eligible for inclusion. The outcomes were mortality analysed at 28- and 90-days as well as at the end of observation and morbidity measured using days alive and free of (DAF) invasive ventilation (DAF ventilation) and DAF circulatory support, including vasopressors or inotropes (DAF circulation), maximum Sequential Organ Failure Assessment score (SOFAmax) the first 28 days after admission and length of stay. All outcomes were analysed in separate multivariable regression models adjusted for age and sex. In addition, in a sensitivity analysis, five subgroups of patients with the main diagnoses sepsis, septic shock, acute respiratory distress syndrome, cardiac arrest and trauma were analysed using the same separate multivariable regression models. RESULTS: In total, 29,512 unique patients were included in the analyses. There were no significant differences for any of the outcomes between non-O blood groups and blood group O, or between RhD blood groups. In the sensitivity analysis of subgroups, there were no differences in mortality between non-O blood groups and blood group O or between the RhD blood groups. AB was the most common blood group in the COVID-19 cohort. CONCLUSIONS: The ABO and RhD blood group do not influence mortality or morbidity in a general critically ill patient population.
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| 9. |
- Larrosa Pardo, F, et al.
(författare)
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A diagnosis of rheumatoid arthritis, endometriosis or IBD is associated with later onset of fibromyalgia and chronic widespread pain
- 2019
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Ingår i: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 23:8, s. 1563-1573
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Widespread pain is a common comorbidity in several chronic diseases and is suspected to be caused by the underlying disease that has provoked a state of central sensitization. However, this argument is currently limited by evidence that has not sufficiently captured the temporal nature of the relationship between diagnosis of the underlying disease and onset of widespread pain. The aim of this study was to investigate whether patients with rheumatoid arthritis (RA), endometriosis or inflammatory bowel disease (IBD) have a higher risk of developing widespread pain (fibromyalgia or chronic widespread pain [CWP]).METHODS: Using the Swedish Skåne Healthcare Register of healthcare consultation, a cohort of 889,938 adult patients were followed from 2007-2016, and incident cases of RA, endometriosis or IBD and of fibromyalgia and CWP were identified by registered diagnoses. Using Poisson regression, we calculated incidence rate ratios (IRR) adjusted for sex, age, education, and propensity to seek health care.RESULTS: For patients with RA, the IRR for later fibromyalgia was 3.64 (95% CI: 2.75-4.81) compared to patients without RA, and for CWP the figure was 2.96 (95% CI: 1.81-4.86). For endometriosis patients, the IRR for fibromyalgia was 2.83 (95% CI: 1.96-4.08) and for CWP 5.02 (95% CI: 3.10-8.13). IRR for IBD patients was 2.32 (95% CI: 1.58-3.42) for fibromyalgia and 1.42 (95% CI: 0.93-2.17) for CWP.CONCLUSIONS: This study shows that RA, endometriosis and IBD are all risk factors for later fibromyalgia and chronic widespread pain, consistent with a hypothesis of central sensitization as an effect of a painful underlying condition.
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