| 1. |
- Stacey, Simon N, et al.
(författare)
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A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103
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Tidskriftsartikel (refereegranskat)abstract
- To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
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| 2. |
- Gretarsdottir, Solveig, et al.
(författare)
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Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 71-692
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
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| 3. |
- Helgadottir, Anna, et al.
(författare)
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Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism
- 2012
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 60:8, s. 722-729
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. Methods The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (ne = 4,572); venous thromboembolism (ne = 4,607); intracranial aneurysm (ne = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). Results LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 X 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 x 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 x 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 x 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 x 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). Conclusions LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes. (J Am Coll Cardiol 2012; 60: 722-9) (C) 2012 by the American College of Cardiology Foundation
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| 4. |
- Jenab, M, et al.
(författare)
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Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition
- 2006
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 95:3, s. 406-415
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Tidskriftsartikel (refereegranskat)abstract
- Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.
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| 5. |
- Scandariato, G., et al.
(författare)
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CHEOPS (CHaracterizing ExOPlanets Satellite) Mission
- 2016
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Ingår i: Proceedings of Science. - 1824-8039. ; 2016-May
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Tidskriftsartikel (refereegranskat)abstract
- The Characterizing ExOPlanet Satellite (CHEOPS) mission was selected in October 2012 by ESA as the first small mission. It will be a ultra-high precision photometer dedicated to the observation of transits of known exoplanets on bright stars, for which the mass has already been measured via ground-based spectroscopic surveys. Its precision will allow the accurate determination of the planetary radii and, by consequence, the planetary bulk density. CHEOPS will also unveil transiting exoplanets of interest for in-depth characterization, a legacy for future instruments suited to the spectroscopic characterization of exoplanetary atmospheres.
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| 6. |
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| 7. |
- Árnadóttir, Thóra, et al.
(författare)
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Glacial rebound and plate spreading : results from the first countrywide GPS observations in Iceland
- 2009
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Ingår i: Geophysical Journal International. - 0956-540X .- 1365-246X. ; 177:2, s. 691-716
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Forskningsöversikt (refereegranskat)abstract
- Iceland is one of the few places on Earth where a divergent plate boundary can be observed on land. Direct observations of crustal deformation for the whole country are available for the first time from nationwide Global Positioning System (GPS) campaigns in 1993 and 2004. The plate spreading across the island is imaged by the horizontal velocity field and high uplift rates (>= 10 mm yr(-1)) are observed over a large part of central and southeastern Iceland. Several earthquakes, volcanic intrusions and eruptions occurred during the time spanned by the measurements, causing local disturbances of the deformation field. After correcting for the largest earthquakes during the observation period, we calculate the strain rate field and find that the main feature of the field is the extension across the rift zones, subparallel to the direction of plate motion. Kinematic models of the horizontal plate spreading signal indicate a slightly elevated rate of spreading in the Northern Volcanic Zone (NVZ) (23 +/- 2 mm yr(-1)), while the rates at the other plate boundary segments agree fairly well with the predicted rate of plate spreading (similar to 20 mm yr(-1)) across Iceland. The horizontal ISNET velocities across north Iceland therefore indicate that the excessive spreading rate (>30 mm yr(-1)) observed by GPS in 1987-1992 following the 1975-1984 Krafla rifting episode was significantly slower during 1993-2004. We model the vertical velocities using glacial isostatic adjustment (GIA) due to the recent thinning of the largest glaciers in Iceland. A layered earth model with a 10-km thick elastic layer, underlain by a 30-km thick viscoelastic layer with viscosity 1 x 10(20) Pa s, over a half-space with viscosity similar to 1 x 10(19) Pa s can explain the broad area of uplift in central and southeastern Iceland. A wide area of significant residual uplift ( up to 8 mm yr(-1)) is evident in north Iceland after we subtract the rebound signal from the observed rates, whereas the Reykjanes Peninsula and the Western Volcanic Zone (WVZ) appear to be subsiding at a rate of 4-8 mm yr(-1). We observe a coherent pattern of small but significant residual horizontal motion (up to 3 mm yr(-1)) away from Vatnajokull and the smaller glaciers that is most likely caused by glacial rebound. Our study demonstrates that the velocity field over a large part of Iceland is affected by deglaciation and that this effect needs to be considered when interpreting deformation data to monitor subglacial volcanoes in Iceland.
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| 8. |
- Bergholdt, Regine, et al.
(författare)
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Integrative analysis for finding genes and networks involved in diabetes and other complex diseases
- 2007
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1474-7596 .- 1465-6906. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- We have developed an integrative analysis method combining genetic interactions, identified using type l diabetes genome scan data, and a high-confidence human protein interaction network. Resulting networks were ranked by the significance of the enrichment of proteins from interacting regions. We identified a number of new protein network modules and novel candidate genes/ proteins for type 1 diabetes. We propose this type of integrative analysis as a general method for the elucidation of genes and networks involved in diabetes and other complex diseases.
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| 9. |
- Bergsmark, T., et al.
(författare)
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Long-term survival after liver transplantation for alcohol-related liver disease in the Nordic countries
- 2023
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 58:8, s. 923-30
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesAlcohol-related liver disease (ALD) is among the most common indications for liver transplantation (LTX) in Europe and North America, with good five-year survival rates post-LTX. Here we evaluated survival up to and beyond 20 years after LTX for patients with ALD compared to a comparison group.MethodsPatients with ALD and a comparison group transplanted in the Nordic countries between 1982 and 2020 were included. Data were analyzed using descriptive statistics, Kaplan-Meier curves and predictors of survival were assessed with Cox-regressions.Results831 patients with ALD and 2979 patients in the comparison group were included in the study. Patients with ALD were older at the time of LTX (p < .001) and more likely to be male (p < .001). The estimated median follow-up time was 9.1 years for the ALD-group and 11.1 years for the comparison group. 333 (40.1%) patients with ALD and 1010 (33.9%) patients in the comparison group died during follow-up. The overall survival was impaired for patients with ALD compared to the comparison group (p < .001) and was evident for male and female patients, patients transplanted before and after 2005, and observed in all age-groups except patients over 60 years. Age at transplant, waiting time, year of LTX and country of LTX were associated with decreased survival after LTX for patients with ALD.ConclusionsPatients with ALD have a decreased long-term survival following LTX. This difference was evident in most sub-groups of patients and warrants close follow-up of liver transplanted patients with ALD with focus on risk reduction.
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| 10. |
- Holland, Stephen T., et al.
(författare)
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GRB 090417B and its host galaxy : a step toward an understanding of optically dark gamma-ray bursts
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 717:1, s. 223-234
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Tidskriftsartikel (refereegranskat)abstract
- GRB 090417B was an unusually long burst with a T-90 duration of at least 2130 s and a multi-peaked light curve at energies of 15-150 keV. It was optically dark and has been associated with a bright star-forming galaxy at a redshift of 0.345 that is broadly similar to the Milky Way. This is one of the few cases where a host galaxy has been clearly identified for a dark gamma-ray burst (GRB) and thus an ideal candidate for studying the origin of dark bursts. We find that the dark nature of GRB 090417B cannot be explained by high redshift, incomplete observations, or unusual physics in the production of the afterglow. Assuming the standard relativistic fireball model for the afterglow we find that the optical flux is at least 2.5 mag fainter than predicted by the X-ray flux. The Swift/XRT X-ray data are consistent with the afterglow being obscured by a dense, localized sheet of dust approximately 30-80 pc from the burst along the line of sight. Our results suggest that this dust sheet imparts an extinction of A(V) greater than or similar to 12 mag, which is sufficient to explain the missing optical flux. GRB 090417B is an example of a GRBs that is dark due to the localized dust structure in its host galaxy.
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