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Sökning: WFRF:(Cramer W)

  • Resultat 21-30 av 87
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  • Lawrenson, Kate, et al. (författare)
  • Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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  • Lucht, W, et al. (författare)
  • Climatic control of the high-latitude vegetation greening trend and Pinatubo effect
  • 2002
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 296:5573, s. 1687-1689
  • Tidskriftsartikel (refereegranskat)abstract
    • A biogeochemical model of vegetation using observed climate data predicts the high northern latitude greening trend over the past two decades observed by satellites and a marked setback in this trend after the Mount Pinatubo, volcano eruption in 1991. The observed trend toward earlier spring budburst and increased maximum leaf area is produced by the model as a consequence of biogeochemical vegetation responses mainly to changes in temperature. The post-Pinatubo decline in vegetation in 1992-1993 is apparent as the effect of temporary cooling caused by the eruption. High-latitude CO2 uptake during these years is predicted as a consequence of the differential response of heterotrophic respiration and net primary production.
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  • Surendran, Praveen, et al. (författare)
  • Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1151-1161
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
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27.
  • Broberg, C. S., et al. (författare)
  • Long-Term Outcomes After Atrial Switch Operation for Transposition of the Great Arteries
  • 2022
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 80:10, s. 951-963
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: For patients with d-loop transposition of the great arteries (d-TGA) with a systemic right ventricle after an atrial switch operation, there is a need to identify risks for end-stage heart failure outcomes. Objectives: The authors aimed to determine factors associated with survival in a large cohort of such individuals. Methods: This multicenter, retrospective cohort study included adults with d-TGA and prior atrial switch surgery seen at a congenital heart center. Clinical data from initial and most recent visits were obtained. The composite primary outcome was death, transplantation, or mechanical circulatory support (MCS). Results: From 1,168 patients (38% female, age at first visit 29 ± 7.2 years) during a median 9.2 years of follow-up, 91 (8.8% per 10 person-years) met the outcome (66 deaths, 19 transplantations, 6 MCS). Patients experiencing sudden/arrhythmic death were younger than those dying of other causes (32.6 ± 6.4 years vs 42.4 ± 6.8 years; P < 0.001). There was a long duration between sentinel clinical events and end-stage heart failure. Age, atrial arrhythmia, pacemaker, biventricular enlargement, systolic dysfunction, and tricuspid regurgitation were all associated with the primary outcome. Independent 5-year predictors of primary outcome were prior ventricular arrhythmia, heart failure admission, complex anatomy, QRS duration >120 ms, and severe right ventricle dysfunction based on echocardiography. Conclusions: For most adults with d-TGA after atrial switch, progress to end-stage heart failure or death is slow. A simplified prediction score for 5-year adverse outcome is derived to help identify those at greatest risk.
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28.
  • Cramer, W, et al. (författare)
  • Tropical forests and the global carbon cycle: impacts of atmospheric carbon dioxide, climate change and rate of deforestation
  • 2004
  • Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 1471-2970. ; 359:1443, s. 331-343
  • Tidskriftsartikel (refereegranskat)abstract
    • The remaining carbon stocks in wet tropical forests are currently at risk because of anthropogenic deforestation, but also because of the possibility of release driven by climate change. To identify the relative roles of CO2 increase, changing temperature and rainfall, and deforestation in the future, and the magnitude of their impact on atmospheric CO2 concentrations, we have applied a dynamic global vegetation model, using multiple scenarios of tropical deforestation (extrapolated from two estimates of current rates) and multiple scenarios of changing climate (derived from four independent offline general circulation model simulations). Results show that deforestation will probably produce large losses of carbon, despite the uncertainty about the deforestation rates. Some climate models produce additional large fluxes due to increased drought stress caused by rising temperature and decreasing rainfall. One climate model, however, produces an additional carbon sink. Taken together, our estimates of additional carbon emissions during the twenty-first century, for all climate and deforestation scenarios, range from 101 to 367 Gt C, resulting in CO2 concentration increases above background values between 29 and 129 p.p.m. An evaluation of the method indicates that better estimates of tropical carbon sources and sinks require improved assessments of current and future deforestation, and more consistent precipitation scenarios from climate models. Notwithstanding the uncertainties, continued tropical deforestation will most certainly play a very large role in the build-up of future greenhouse gas concentrations.
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