| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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- Kanai, M, et al.
(författare)
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- 2023
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- Bravo, L, et al.
(författare)
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- 2021
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- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 9. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Law, Philip J., et al.
(författare)
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Association analyses identify 31 new risk loci for colorectal cancer susceptibility
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
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| 21. |
- Zhou, Wei, et al.
(författare)
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Global Biobank Meta-analysis Initiative : Powering genetic discovery across human disease
- 2022
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Ingår i: Cell Genomics. - : Elsevier. - 2666-979X. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.
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| 22. |
- Alanazi, W, et al.
(författare)
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Post-Transplant Cyclophosphamide Combined with Anti-Thymocyte Globulin as Graft-versus-Host Disease Prophylaxis for Allogeneic Hematopoietic Cell Transplantation in High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome
- 2021
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Ingår i: Acta haematologica. - : S. Karger AG. - 1421-9662 .- 0001-5792. ; 144:1, s. 66-73
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Allogeneic hematopoietic cell transplantation (HCT) is curative for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) but with significant non-relapse mortality (NRM) and relapse. We compared the combination of anti-thymocyte globulin (ATG; 4.5 mg/kg) and post-transplant cyclophosphamide (PTCy; 50 mg/kg on day +3 and +4) with other graft-versus-host disease (GvHD) prophylaxis regimens used for these patients. <b><i>Methods:</i></b> We retrospectively analyzed 159 patients, aged 22–73 (median 56) years, having undergone transplantation for high-risk AML (<i>n</i> = 120) or MDS (<i>n</i> = 39). The donors were matched related (33%), unrelated (55%) and haploidentical (12%). Almost all patients used peripheral blood stem cells. Conditioning was myeloablative (34%) or reduced intensity (66%). ATG + PTCy was used in 69 patients (43%), and other GvHD prophylaxis regimens in 90 patients (57%). <b><i>Results:</i></b> Grade III–IV acute GvHD occurred in 4% of the ATG + PTCy patients versus 20% of those using other regimens (<i>p</i> = 0.004), and chronic GvHD in 19% of the ATG + PTCy patients versus 41% of those using other regimens (<i>p</i> = 0.003). Two-year GvHD-free relapse-free survival (GRFS) was 30% with ATG + PTCy versus 18% with other regimens (<i>p</i> = 0.04). Multivariable analysis demonstrated that while ATG + PTCy had no significant influence on overall survival, cumulative incidence of relapse or NRM, there was a significant influence on GRFS in favor of ATG + PTCy (HR = 0.69, 95% CI 0.45–0.99, <i>p</i> = 0.04). <b><i>Conclusions:</i></b> We conclude that the ATG + PTCy combination significantly improved GRFS in allogeneic HCT for high-risk AML and MDS without influencing other outcomes.
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| 28. |
- Freitag, Daniel F., et al.
(författare)
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Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
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Tidskriftsartikel (refereegranskat)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
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| 29. |
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| 30. |
- Inamoto, Y., et al.
(författare)
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Non-GVHD ocular complications after hematopoietic cell transplantation: expert review from the Late Effects and Quality of Life Working Committee of the CIBMTR and Transplant Complications Working Party of the EBMT
- 2019
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 54:5, s. 648-661
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Tidskriftsartikel (refereegranskat)abstract
- Non-graft-vs.-host disease (non-GVHD) ocular complications are generally uncommon after hematopoietic cell transplantation (HCT), but can cause prolonged morbidity affecting activities of daily living and quality of life. Here we provide an expert review of non-GVHD ocular complications in a collaboration between transplant physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Complications discussed in this review include cataracts, glaucoma, ocular infections, ocular involvement with malignancy, ischemic microvascular retinopathy, central retinal vein occlusion, retinal hemorrhage, retinal detachment, and ocular toxicities associated with medications. We have summarized incidence, risk factors, screening, prevention and treatment of individual complicastions and generated evidence-based recommendations. Baseline ocular evaluation before HCT should be considered in all patients who undergo HCT. Follow-up evaluations should be considered according to clinical symptoms, signs and risk factors. Better preventive strategies and treatments remain to be investigated for individual ocular complications after HCT. Both transplant physicians and ophthalmologists should be knowledgeable of non-GVHD ocular complications and provide comprehensive collaborative team care.
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| 41. |
- Prem, Shruti, et al.
(författare)
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Relationship between certain HLA alleles and the risk of cytomegalovirus reactivation following allogeneic hematopoietic stem cell transplantation
- 2022
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Ingår i: Transplant Infectious Disease. - : John Wiley & Sons. - 1398-2273 .- 1399-3062. ; 24:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Evidence is emerging to support an association between certain human leukocyte antigen (HLA) alleles and the risk of cytomegalovirus (CMV) reactivation following allogeneic hematopoietic stem cell transplant (allo-HSCT). The primary aim of this study was to identify HLA alleles associated with resistance or susceptibility to CMV reactivation. Methods: We studied 586 adults who underwent al lo-HSCT for high-risk hematological malignancies. High-resolution HLA typing data were available for recipients and donors. HLA class I and II alleles observed at a frequency of >5% in our population were included in the analysis. A CMV viremia level of more than 200 IU/ml on weekly monitoring was considered to be indicative of CMV reactivation. Results: The median follow-up time in surviving patients was 21 months (range 4-74 months). The cumulative incidence of CMV reactivation at 6 months in the entire cohort was 55% (95% confidence interval [CI] 50.8%-59.2%). Mismatched donors, increasing recipient age, occurrence of acute graft versus host disease and recipient CMV seropositivity were associated with an increased risk of CMV reactivation. HLA B*07:02 (hazard ratio 0.59, 95% CI 0.40-0.83) was associated with a decreased risk of CMV reactivation. Patients who developed CMV reactivation had a lower incidence of relapse, higher transplant-related mortality (TRM) and lower overall survival (OS) than those without CMV reactivation. There was an adverse correlation of OS and TRM with increasing numbers of CMV reactivations. Conclusion: We observed that HLA B*07:02 was associated with a decreased risk of CMV reactivation. CMV reactivation was associated with lower relapse post-transplant, but this did not translate into a survival benefit due to higher TRM.
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| 42. |
- Queralt Salas, Maria, et al.
(författare)
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High incidence but low mortality of EBV-reactivation and PTLD after alloHCT using ATG and PTCy for GVHD prophylaxis
- 2020
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 61:13, s. 3198-3208
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Tidskriftsartikel (refereegranskat)abstract
- We explore risk factors and impacts of post-transplant EBV-Reactivation (EBV-R) and PTLD in 270 patients that underwent RIC alloHCT using ATG-PTCy and cyclosporine for GVHD prophylaxis. Twenty-five (12%) patients had probable (n = 7) or proven (n = 18) PTLD. Patients were managed with reduction of immunosuppression and 22 with weekly rituximab (375 mg/m2 IV). ORR was 84%; 8 (32%) recipients died, and one-year OS and NRM of patients with PTLD was 59.7% and 37%, respectively. One hundred seventy-two (63.7%) recipients had EBV-R. One-year OS and RFS of patients with EBV-R were 68.2% and 60.6%, and of EBV-Negative patients were 62.1% and 50.1%, respectively. High incidence but low mortality of EBV-R and PTLD was documented. EBV-R induced a protective effect on RFS in multivariable analysis (HR 0.91, p = .011). Therefore, EBV-R may have a protective effect on RFS in this setting. Further research is necessary to evaluate the interplay of EBV-R, immune reconstitution, and post-transplant outcomes.
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