| 1. |
- Went, M, et al.
(författare)
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Author Correction: Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 213-
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Tidskriftsartikel (refereegranskat)abstract
- The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.
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| 2. |
- Went, M, et al.
(författare)
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Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3707-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.
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| 5. |
- 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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| 6. |
- Ali, Mina, et al.
(författare)
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The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 1649-
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we identified ELL2 as a susceptibility gene for multiple myeloma (MM). To understand its mechanism of action, we performed expression quantitative trait locus analysis in CD138+ plasma cells from 1630 MM patients from four populations. We show that the MM risk allele lowers ELL2 expression in these cells (Pcombined = 2.5 × 10−27; βcombined = −0.24 SD), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause–effect relationship. Our results provide mechanistic insight into MM predisposition.
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| 7. |
- Jonsson, Stefan, et al.
(författare)
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Identification of sequence variants influencing immunoglobulin levels
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49:8, s. 1182-1191
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and influence blood cell development. Notable associations include a rare variant at RUNX3 decreasing IgA levels by shifting isoform proportions (rs188468174[C>T]: P = 8.3 × 10(-55), β = -0.90 s.d.), a rare in-frame deletion in FCGR2B abolishing IgG binding to the encoded receptor (p.Asn106del: P = 4.2 × 10(-8), β = 1.03 s.d.), four IGH locus variants influencing class switching, and ten new associations with the HLA region. Our results provide new insight into the regulation of humoral immunity.
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| 9. |
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| 10. |
- Rönnblad, E, et al.
(författare)
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[Elbow injuries in children]
- 2016
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Ingår i: Lakartidningen. - 1652-7518. ; 113
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Tidskriftsartikel (refereegranskat)
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| 11. |
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| 12. |
- Thorin, M. H., et al.
(författare)
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Smoking, smoking cessation, and fracture risk in elderly women followed for 10 years
- 2016
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Ingår i: Osteoporosis International. - Stockholm : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 27:1, s. 249-255
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Tidskriftsartikel (refereegranskat)abstract
- Summary: This study examines the impact of smoking and smoking cessation on fracture risk in 75-year-old women followed for 10 years. Smoking increased fracture risk, especially for vertebral fractures. Smoking cessation decreased the risk for vertebral fractures but not for other fracture types. Introduction: The purpose of this study was to examine effects of smoking and smoking cessation on fracture risk. Methods: This prospective observational population-based study followed 1033 women during 10 years from age 75. Data regarding smoking were collected at age 75. Hazard ratios (HRs) and 95 % confidence intervals for fracture were calculated using competing risks proportional hazards regression. Results: Both former smokers and current smokers had an increased risk for any fracture (HR 1.30; 1.03–1.66, and HR 1.32; 1.01–1.73, respectively) and any osteoporotic fracture (hip, proximal humerus, distal radius, vertebra) (HR 1.31; 1.01–1.70 and HR 1.49; 1.11–1.98, respectively) compared to non-smokers. Former smokers had an increased risk for proximal humerus fractures (HR 2.23; 1.35–3.70), and current smokers had an increased risk for vertebral fractures (HR 2.30; 1.57–3.38) compared to non-smokers. After adjustment for weight, previous fractures, alcohol habits, bone mineral density (BMD), use of corticoids, vitamin D, bisphosphonates, and previous falls, former smokers had an increased risk for proximal humerus fracture (HR 2.07; 1.19–3.57) and current smokers had an increased risk for osteoporotic (HR 1.47; 1.05–2.05) and vertebral fractures (HR 2.50; 1.58–3.95) compared to non-smokers. Former smokers had a decreased risk for vertebral fractures, but not for other types of fractures, compared to current smokers. Conclusions: Smoking increased the risk for fracture among elderly women, especially vertebral fractures. Smoking cessation decreased the risk for vertebral fractures but not for other types of fractures.
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| 14. |
- Wihlborg, A., et al.
(författare)
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Fracture predictive ability of physical performance tests and history of falls in elderly women: a 10-year prospective study
- 2015
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 26:8, s. 2101-2109
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Tidskriftsartikel (refereegranskat)abstract
- A Summary In a large cohort of elderly women followed for 10 years, we found that balance, gait speed, and self-reported history of fall independently predicted fracture. These clinical risk factors are easily evaluated and therefore advantageous in a clinical setting. They would improve fracture risk assessment and thereby also fracture prevention. Introduction The aim of this study was to identify additional risk factors for osteoporosis-related fracture by investigating the fracture predictive ability of physical performance tests and self-reported history of falls. Methods In the population-based Osteoporosis Prospective Risk Assessment study (OPRA), 1044 women were recruited at the age of 75 and followed for 10 years. At inclusion, knee extension force, standing balance, gait speed, and bone mineral density (BMD) were examined. Falls the year before investigation was assessed by questionnaire. Cox proportional hazards regression analysis was used to determine fracture hazard ratios (HR) with BMD, history of fracture, BMI, smoking habits, bisphosphonate, vitamin D, glucocorticoid, and alcohol use as covariates. Continuous variables were standardized and HR shown for each standard deviation change. Results Of all women, 427 (41 %) sustained at least one fracture during the 10-year follow-up. Failing the balance test had an HR of 1.98 (1.18-3.32) for hip fracture. Each standard deviation decrease in gait speed was associated with an HR of 1.37 (1.14-1.64) for hip fracture. Previous fall had an HR of 1.30 (1.03-1.65) for any fracture; 1.39 (1.08-1.79) for any osteoporosis-related fracture; and 1.60 (1.03-2.48) for distal forearm fracture. Knee extension force did not show fracture predictability. Conclusion The balance test, gait speed test, and self-reported history of fall all hold independent fracture predictability. Consideration of these clinical risk factors for fracture would improve the fracture risk assessment and subsequently also fracture prevention.
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