| 1. |
- Bernatsky, Sasha, et al.
(author)
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Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma
- 2017
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In: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 4:1
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Journal article (peer-reviewed)abstract
- Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE.
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| 2. |
- Berndt, Sonja, I, et al.
(author)
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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- 2022
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In: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
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Journal article (peer-reviewed)abstract
- Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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| 3. |
- Cerhan, James R., et al.
(author)
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Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma
- 2014
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:11, s. 1233-1238
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Journal article (peer-reviewed)abstract
- Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 x 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 x 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 x 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 x 10(-13) and 3.63 x 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.
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| 4. |
- Din, Lennox, et al.
(author)
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Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes
- 2019
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In: Genetic Epidemiology. - : WILEY. - 0741-0395 .- 1098-2272. ; 43:7, s. 844-863
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Journal article (peer-reviewed)abstract
- Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p =.0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.
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| 5. |
- Falahati-Anbaran, Mohsen, et al.
(author)
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Contrasting Patterns of Genetic Structuring in Natural Populations of Arabidopsis lyrata Subsp petraea across Different Regions in Northern Europe
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:9, s. e107479-
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Journal article (peer-reviewed)abstract
- Level and partitioning of genetic diversity is expected to vary between contrasting habitats, reflecting differences in strength of ecological and evolutionary processes. Therefore, it is necessary to consider processes acting on different time scales when trying to explain diversity patterns in different parts of species' distributions. To explore how historical and contemporary factors jointly may influence patterns of genetic diversity and population differentiation, we compared genetic composition in the perennial herb Arabidopsis lyrata ssp. petraea from the northernmost parts of its distribution range on Iceland to that previously documented in Scandinavia. Leaf tissue and soil were sampled from ten Icelandic populations of A. lyrata. Seedlings were grown from soil samples, and tissue from above-ground and seed bank individuals were genotyped with 21 microsatellite markers. Seed bank density in Icelandic populations was low but not significantly different from that observed in Norwegian populations. While within-population genetic diversity was relatively high on Iceland (H-E = 0.35), among-population differentiation was low (F-ST = 0.10) compared to Norwegian and Swedish populations. Population differentiation was positively associated with geographical distance in both Iceland and Scandinavia, but the strength of this relationship varied between regions. Although topography and a larger distribution range may explain the higher differentiation between mountainous Norwegian relative to lowland populations in Sweden, these factors cannot explain the lower differentiation in Icelandic compared to Swedish populations. We propose that low genetic differentiation among Icelandic populations is not caused by differences in connectivity, but is rather due to large historical effective population sizes. Thus, rather than contemporary processes, historical factors such as survival of Icelandic lineages in northern refugia during the last glacial period may have contributed to the observed pattern.
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| 6. |
- Kahlin, Magnus, 1982-
(author)
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3D-printing for Aerospace : Fatigue Behaviour of Additively Manufactured Titanium
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Laser powder bed fusion (L-PBF) and electron beam powder bed fusion (E-PBF) are two of the most common additive manufacturing (AM) methods which both provide the engineer with a great freedom of design.This means that parts with light weight, multifunctional applications and improved performance could be achieved through innovative design solutions which have attracted a lot of interest from the aerospace industry.This PhD project has focused on the following fatigue related areas forL-PBF and E-PBF Ti6Al4V material which all need to be addressed before AM can be fully introduced to critical aerospace applications: effect of geometry, roughness and loading on fatigue life, improved fatigue life through post processing, fatigue crack growth behaviour and fatigue prediction methods.The results show that the rough as-built surface is the single most severe factor for fatigue but that the fatigue strength of at least L-PBF material can be improved to levels similar to conventionally manufactured material using surface post processing. Furthermore, the results verify that acumulative damage approach gives good accuracy in predicting fatigue life for variable amplitude loading and that fatigue crack growth rates using material data from standard specimens can be used for damage tolerancean alysis independent of part geometry and stress level.The conclusion is therefore that the fatigue properties can be improved to acceptable levels and predicted using conventional methods. There are still some challenges to solve, however, especially within non-destructive testing before AM can be introduced to critical aerospace applications.
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| 7. |
- Kahlin, Magnus, et al.
(author)
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Fatigue behaviour of additive manufactured Ti6Al4V, with as-built surfaces, exposed to variable amplitude loading
- 2017
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In: International Journal of Fatigue. - : ELSEVIER SCI LTD. - 0142-1123 .- 1879-3452. ; 103, s. 353-362
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Journal article (peer-reviewed)abstract
- Additive Manufacturing (AM) allows for great design freedom compared to conventional manufacturing. This is very attractive for the aerospace industry in which AM could contribute to lightweight designs and thereby reduce fuel consumption, increase payload and extend flight range. The fatigue behaviour for rough as-built AM surfaces has previously been characterized with constant amplitude testing but in aerospace applications, most parts are exposed to variable amplitude loading. The fatigue behaviour for variable amplitude is not always consistent with the behaviour for constant amplitude due to effects of overloads and local plastic deformations. Therefore, variable amplitude loading behaviour of laser sintered and electron beam melted Ti6Al4V, with rough as-built surfaces have been investigated in this study using the Short-FALSTAFF (Fighter Aircraft Loading STAndard For Fatigue) load sequence. The predicted and the experimental fatigue life was overall consistent even though most experimental results exceeded the predicted life, especially for the laser sintered material. These findings show that conventional cumulative damage fatigue life predictions give reliable predictions for AM materials with rough as-built surfaces for the type of tension dominated load sequence used. (C) 2017 Elsevier Ltd. All rights reserved.
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| 8. |
- Kahlin, Magnus, et al.
(author)
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Fatigue Behaviour of Notched Additive Manufactured Ti6Al4V with As-built Surfaces
- 2017
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In: International Journal of Fatigue. - : Elsevier. - 0142-1123 .- 1879-3452. ; :101, s. 51-60
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Journal article (peer-reviewed)abstract
- Additive manufacturing (AM) allows the manufacturer to produce parts with complex geometries that are difficult to produce with conventional production methods. Generally, AM is considered to have great potential for the aerospace industry by contributing to reduced weight and lower costs. There are a number of challenges to be solved before AM can be fully utilized in the aerospace industry, and the understanding of fatigue behaviour is one of the major challenges. Although the fatigue properties of flat additive manufactured specimens with rough as-built surfaces already have been widely studied, in practice, few aerospace components have a simple flat geometry with no corners or radii that would act as stress concentrations. Therefore, the combined effect on fatigue life of a rough as-built surface and a geometrical notch needs to be established. In this study, the fatigue properties of both laser sintered and electron beam melted Ti6Al4V have been investigated and a combined effect of a rough as-built surface and a geometrical notch has been determined. In addition, hot isostatic pressing was found to have no impact on fatigue life for rough as-built surfaces. These findings can be directly applied to predict fatigue behaviour of an AM industrial component.
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| 9. |
- Kahlin, Magnus, 1982-, et al.
(author)
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Fatigue crack growth for through and part-through cracks in additively manufactured Ti6Al4V
- 2022
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In: International Journal of Fatigue. - : Elsevier. - 0142-1123 .- 1879-3452. ; 155
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Journal article (peer-reviewed)abstract
- Critical aerospace parts require damage tolerance analysis to determine the inspection intervals in-service. Such analyses, based on linear fracture mechanics, require that the fatigue crack growth (FCG) rate relation to the stress intensity factor range is applicable independent of geometry and stress. FCG rates for laser powder bed fusion Ti6Al4V material for conventional compact tension (CT) specimens have therefore been compared to FCG rates for specimens with a crack configuration more technically relevant from an industrial and engineering perspective. The FCG rates corresponded very well and data obtained with CT-specimens can therefore be considered relevant for general damage tolerance predictions.
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| 10. |
- Kahlin, Magnus
(author)
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Fatigue Performance of Additive Manufactured Ti6Al4V in Aerospace Applications
- 2017
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Licentiate thesis (other academic/artistic)abstract
- Additive Manufacturing (AM) for metals includes is a group of production methodst hat use a layer-by-layer approach to directly manufacture final parts. In recent years, the production rate and material quality of additive manufactured materials have improved rapidly which has gained increased interest from the industry to use AM not only for prototyping, but for serial production. AM offers a greater design freedom, compared to conventional production methods, which allows for parts with new innovative design. This is very attractive to the aerospace industry, in which parts could be designed to have reduced weight and improved performance contributing to reduced fuel consumption, increased payload and extended flight range. There are, however, challenges yet to solve before the potential of AM could be fully utilized in aerospace applications. One of the major challenges is how to deal with the poor fatigue behaviour of AM material with rough as-built surface.The aim of this thesis is to increase the knowledge of how AM can be used for high performance industrial parts by investigating the fatigue behaviour of the titanium alloy Ti6Al4V produced with different AM processes. Foremost, the intention is to improve the understanding of how rough as-built AM surfaces in combination with AM built geometrical notches affects the fatigue properties.This was done by performing constant amplitude fatigue testing to compare different combinations of AM material produced by Electron Beam Melting(EBM) and Laser Sintering (LS) with machined or rough as-built surfaces with or without geometrical notches and Hot Isostatic Pressing (HIP) treatment. Furthermore, the material response can be different between constant amplitude and variable amplitude fatigue loading due to effects of overloads and local plastic deformations. The results from constant amplitude testing were used to predict the fatigue life for variable amplitude loading by cumulative damage approach and these predictions were then verified by experimental variable amplitude testing.The constant amplitude fatigue strength of material with rough as-built surfaces was found to be 65-75 % lower, compared to conventional wrought bar, in which HIP treatments had neglectable influence on the fatigue strength. Furthermore, the fatigue life predictions with cumulative damage calculations showed good agreement with the experimental results which indicates that a cumulative damage approach can be used, at least for a tensile dominated load sequences, to predict the fatigue behaviour of additive manufactured Ti6Al4V.
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