| 1. |
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| 2. |
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| 3. |
- Berndt, Sonja, I, et al.
(författare)
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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- 2022
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Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Law, PJ, et al.
(författare)
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Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 14175-
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Tidskriftsartikel (refereegranskat)abstract
- Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
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| 5. |
- Berndt, Sonja I., et al.
(författare)
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Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
- 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
- Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P = 2.55 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
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| 6. |
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| 7. |
- Cuzzone, Joshua K., et al.
(författare)
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Final deglaciation of the Scandinavian Ice Sheet and implications for the Holocene global sea-level budget
- 2016
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Ingår i: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X .- 1385-013X. ; 448, s. 34-41
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Tidskriftsartikel (refereegranskat)abstract
- The last deglaciation of the Scandinavian Ice Sheet (SIS) from similar to 21,000 to 13,000 yr ago is well constrained by several hundred Be-10 and C-14 ages. The subsequent retreat history, however, is established primarily from minimum-limiting C-14 ages and incomplete Baltic-Sea varve records, leaving a substantial fraction of final SIS retreat history poorly constrained. Here we develop a high-resolution chronology for the final deglaciation of the SIS based on 79 Be-10 cosmogenic exposure dates sampled along three transects spanning southern to northern Sweden and Finland. Combining this new chronology with existing Be-10 ages on deglaciation since the Last Glacial Maximum shows that rates of SIS margin retreat were strongly influenced by deglacial millennial-scale climate variability and its effect on surface mass balance, with regional modulation of retreat associated with dynamical controls. Ice-volume estimates constrained by our new chronology suggest that the SIS contributed 8 m sea-level equivalent to global sea-level rise between similar to 14.5 ka and 10 ka. Final deglaciation was largely complete by similar to 10.5 ka, with highest rates of sea-level rise occurring during the Bolling-Allerod, a 50% decrease during the Younger Dryas, and a rapid increase during the early Holocene. Combining our SIS volume estimates with estimated contributions from other remaining Northern Hemisphere ice sheets suggests that the Antarctic Ice Sheet (AIS) contributed 14.4 +/- 5.9 m to global sea-level rise since 13 ka. This new constraint supports those studies that indicate that an ice volume of 15 m or more of equivalent sea-level rise was lost from the AIS during the last deglaciation.
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| 8. |
- Johansson, Jan, 1960, et al.
(författare)
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Continuous GPS measurements of postglacial adjustment in Fennoscandia - 1. Geodetic results
- 2002
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 107:B8
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Tidskriftsartikel (refereegranskat)abstract
- Project BIFROST (Baseline Inferences for Fennoscandian Rebound Observations, Sea-level, and Tectonics) combines networks of continuously operating GPS receivers in Sweden and Finland to measure ongoing crustal deformation due to glacial isostatic adjustment (GIA). We present an analysis of data collected between August 1993 and May 2000. We compare the GPS determinations of three-dimensional crustal motion to predictions calculated using the high-resolution Fennoscandian deglaciation model recently proposed by Lambeck et al. [1998a, 1998b]. We find that the maximum observed uplift rate (~10 mm/yr) and the maximum predicted uplift rate agree to better than 1 mm yr-1. The patterns of uplift also agree quite well, although significant systematic differences are evident. The root-mean-square residual rate for a linear error model yields estimates of rate accuracy of 0.4 mm/yr for east, 0.3 mm/yr for north, and 1.3 mm/yr for up; these figures incorporate model errors, however. We have also compared the values for the observed radial deformation rates to those based on sea level rates from Baltic tide gauges. The observational error for the vertical GPS rates required to give a reduced chi^2 of unity is 0.8 mm/yr. The time series do exhibit temporal variations at seasonal frequencies, as well as apparent low-frequency noise. An empirical orthogonal function analysis indicates that the temporal variations are highly correlated among the sites. The correlation appears to be regional and falls off only slightly with distance. Some of this correlated noise is associated with snow accumulation on the antennas or, for those antennas with radomes, on the radomes. This problem has caused us to modify the radomes used several times, leading to one of our more significant sources of uncertainty.
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| 9. |
- Moore, Amy, et al.
(författare)
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Genetically Determined Height and Risk of Non-hodgkin Lymphoma
- 2020
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Ingår i: Frontiers in Oncology. - : FRONTIERS MEDIA SA. - 2234-943X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
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| 10. |
- Wang, Sophia S., et al.
(författare)
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HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
- 2018
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:14, s. 4086-4096
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Tidskriftsartikel (refereegranskat)abstract
- A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma.
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| 11. |
- Din, Lennox, et al.
(författare)
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Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes
- 2019
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Ingår i: Genetic Epidemiology. - : WILEY. - 0741-0395 .- 1098-2272. ; 43:7, s. 844-863
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Tidskriftsartikel (refereegranskat)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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| 12. |
- Glueder, Anna, et al.
(författare)
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Calibrated relative sea levels constrain isostatic adjustment and ice history in northwest Greenland
- 2022
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 293
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Tidskriftsartikel (refereegranskat)abstract
- Relative Sea Levels (RSLs) derived primarily from marine bivalves near Petermann Glacier, NW Greenland, constrain past regional ice-mass changes through glacial isostatic adjustment (GIA) modeling. Oxygen isotopes measured on bivalves corrected for shell-depth habitat and document changing meltwater input. Rapid RSL fall of up to 62 m/kyr indicates ice loss at or prior to ∼9 ka. Transition to an RSL stillstand starting at ∼6 ka reflects renewed ice-mass loading followed by further mass loss over the past few millennia. GIA simulations of rapid early RSL fall suggest a low regional upper-mantle viscosity. Early loss of grounded ice tracks atmospheric warming and pre-dates the eventual collapse of Petermann Glacier's floating ice tongue near ∼7 ka, suggesting grounding zone stabilization during early phases of deglaciation. We hypothesize mid-Holocene regrowth of regional ice caps in response to cooling and increased precipitation, following loss of the floating shelf ice. Remnants of these ice caps remain present but are now melting.
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| 13. |
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| 14. |
- Lidberg, Martin, 1964, et al.
(författare)
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Recent results based on continuous GPS observations of the GIA process in Fennoscandia from BIFROST
- 2010
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Ingår i: Journal of Geodynamics. - : Elsevier BV. - 0264-3707. ; 50:1, s. 8-18
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Tidskriftsartikel (refereegranskat)abstract
- We present the latest 3D velocity field of the Fennoscandian glacial isostatic adjustment (GIA) processfrom BIFROST. It is derived from more than 4800 days (13 years) of data at more than 80 permanentGPS sites. We use the GAMIT/GLOBK and the GIPSY/OASIS II software packages for GPS analysis andcompare the results. The solution has an internal accuracy at the level of 0.2 mm/year (1 sigma) forhorizontal velocities at the best sites.Wealso present a revised GIA prediction model. At the best sites, theoptimal model agrees with the observations to within 0.4 mm/year. However, the model systematicallyoverpredicts the magnitude of horizontal rates in the north. We discuss limitations in computed andpresented GNSS station velocities, where especially possible instability over time causing non-linearpattern in vertical time series are considered. In extension, preliminary results from an investigationapplying revised analysis strategies on a sparse subset of the database are presented, indicating possibleimprovements for the future.
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| 15. |
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| 16. |
- Milne, Glenn A., et al.
(författare)
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Space-Geodetic Constraints on Glacial Isostatic Adjustment in Fennoscandia
- 2001
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Ingår i: Science. - 0036-8075 .- 1095-9203. ; 291:23 March 2001, s. 2381-2385
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of Global Positioning System (GPS) data demonstrates that ongoing three-dimensional crustal deformation in Fennoscandia is dominated by glacial isostatic adjustment. Our comparison of these GPS observations with numerical predictions yields an Earth model that satisÞes independent geologic constraints and bounds both the average viscosity in the upper mantle (5 x 10^20 to 1 x 10^21 pascal seconds) and the elastic thickness of the lithosphere (90 to 170 kilometers). We combined GPS-derived radial motions with Fennoscandian tide gauge records to estimate a regional sea surface rise of 2.1 +- 0.3 mm/year. Furthermore, ongoing horizontal tectonic motions greater than ~1 mm/year are ruled out on the basis of the GPS-derived three-dimensional crustal velocity field.
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| 17. |
- Olsson, Per-Anders, 1971, et al.
(författare)
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The relation between gravity rate of change and vertical displacement in previously glaciated areas
- 2015
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Ingår i: Journal of Geodynamics. - : Elsevier BV. - 0264-3707. ; 83, s. 76-84
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Tidskriftsartikel (refereegranskat)abstract
- The rate of change of surface gravity, dg/dt, and vertical deformation rate of the solid surface, du/dt, are two observables of glacial isostatic adjustment (GIA). They contribute with different information on the same phenomenon. Their relation contains information of the underlying physics and a trustworthy relation allows to combine these observations to strengthen the overall observational accuracy of the phenomenon. In this paper we investigate the predicted relation between dg/dt and du/dt in previously glaciated areas. We use the normal mode approach for one dimensional earth models and solutions of the sea level equation with time-dependent coastline geometry. Numerical predictions of dg/dt and du/dt are computed for Laurentia, Fennoscandia and the British Isles respectively, using six different earth models. Within each region a linear trend is then fitted using the relation dg/dt = C du/dt + dg_0/dt. The estimated C and dg_0/dt differ more between the regions than between different earth models within each region. For Fennoscandia C ≈ −0.163 μGal/mm and for Laurentia C ≈ −0.152 μGal/mm. Maximum residuals between the linear trend and spatially varying model predictions of dg/dt are 0.04 μGal/yr in Fennoscandia and 0.17 μGal/yr in Laurentia. For the British Isles the results are harder to interpret, mainly since this region is located on the zero uplift isoline of Fennoscandia. In addition, we show temporal variation of the relation since the last glacial maximum till present-day. The temporal and spatial variation of the relation between dg/dt and du/dt can be explained by (i) the elastic respectively viscous proportion of the total signal and (ii) the spectral composition of the regional signal. Additional local effects, such as the Newtonian attraction and elastic deformation from local sea level changes, are examined in a case study for six stations in the Nordic absolute gravity network. The influence of these local effects on the relation between View the dg/dt and du/dt is negligible except for extreme locations close to the sea.
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| 18. |
- Scherneck, Hans-Georg, 1951, et al.
(författare)
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Fennoscandian strain rates from BIFROST GPS: A gravitating, thick-plate approach
- 2010
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Ingår i: Journal of Geodynamics. - : Elsevier BV. - 0264-3707. ; 50:1, s. 19-26
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this investigation is to develop a method for the analysis of crustal strain determined bystation networks that continuously measurements of Global Navigation Satellite Systems (GNSS). Themajor new ingredient is that we require a simultaneous minimum of the observation error and theelastic and potential energy implied by the deformation.The observations that we analyse come from eight years worth of daily solutions from continuousBIFROST GPS measurements in the permanent networks of the Nordic countries and their neighbours.Reducing the observations with best fitting predictions for the effects of glacial isostatic adjustment (GIA)we find strain rates of maximum 5 nano/yr in the interior of the rebound area predominantly as arealstrain. The largest strain rates are found in the Finnmarken area, where however the GNSS networkdensity is much lower than in the central and southern parts.The thick-plate adjustment furnishes a simultaneous treatment of 3-D displacements and the ensuingelastic and potential energy due to the deformation. We find that the strain generated by flexure due toGIA is important. The extensional regime seen at the surface turns over into a compressive style alreadyat moderated depth, some 50 km.
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| 19. |
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