| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 3. |
- Surakka, Ida, et al.
(författare)
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The impact of low-frequency and rare variants on lipid levels.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:6, s. 589-597
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Tidskriftsartikel (refereegranskat)abstract
- Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.
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| 4. |
- Vimaleswaran, Karani S, et al.
(författare)
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Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.
- 2014
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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595 .- 2213-8587. ; 2:9, s. 719-29
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Tidskriftsartikel (refereegranskat)abstract
- Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
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| 5. |
- Adman, Per, et al.
(författare)
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171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
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Ingår i: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
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| 6. |
- Baiocchi, B., et al.
(författare)
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Transport analysis and modelling of the evolution of hollow density profiles plasmas in JET and implication for ITER
- 2015
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Ingår i: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 55:12
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Tidskriftsartikel (refereegranskat)abstract
- The density evolution during the transient phase just after the L-H transition is investigated using theoretical transport models. Cases characterized by core densities which evolve in longer timescales than the edge densities, leading to hollow density profiles (R/L-n = -R del n/n < 0) are modelled. This density evolution is particularly interesting because it has been shown to be beneficial in the view of the access to burning plasma conditions in ITER (Loarte et al 2013 Nucl. Fusion 53 083031). Self-consistent simulations of the JET discharge 79676 of the density-only, and of the density and the temperatures are carried out using a quasilinear gyrokinetic code, QuaLiKiz (Bourdelle et al 2007 Phys. Plasmas 14 112501), coupled with a transport code CRONOS (Artaud et al 2010 Nucl. Fusion 50 043001). The slow evolution of the hollow density, associated with the self-consistently calculated hollow NBI particle deposition, is well reproduced in the plasma core. Indeed, QuaLiKiz is shown to reproduce nonlinear gyrokinetic heat and particle fluxes well for both positive and negative R/L-n. That gives a theoretical and general basis for the persistence of the hollowness, laying the groundwork for the extrapolation to ITER.
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| 7. |
- Baiocchi, B., et al.
(författare)
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Turbulent transport analysis of JET H-mode and hybrid plasmas using QuaLiKiz and Trapped Gyro Landau Fluid
- 2015
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 57:3
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Tidskriftsartikel (refereegranskat)abstract
- The physical transport processes at the basis of JET typical inductive H-mode scenarios and advanced hybrid regimes, with improved thermal confinement, are analyzed by means of some of the newest and more sophisticated quasi-linear transport models: trapped gyro Landau fluid (TGLF) and QuaLiKiz. The temporal evolution of JET pulses is modelled by CRONOS where the turbulent transport is modelled by either QuaLiKiz or TGLF. Both are first principle models with a more comprehensive physics than the models previously developed and therefore allow the analysis of the physics at the basis of the investigated scenarios. For H-modes, ion temperature gradient (ITG) modes are found to be dominant and the transport models are able to properly reproduce temperature profiles in self-consistent simulations. However, for hybrid regimes, in addition to ITG trapped electron modes (TEM) are also found to be important and different physical mechanisms for turbulence reduction play a decisive role. Whereas E x B flow shear and plasma geometry have a limited impact on turbulence, the presence of a large population of fast ions, quite important in low density regimes, can stabilize core turbulence mainly when the electromagnetic effects are taken into account. The TGLF transport model properly captures these mechanisms and correctly reproduces temperatures.
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| 8. |
- Baron-Wiechec, A., et al.
(författare)
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First dust study in JET with the ITER-like wall : sampling, analysis and classification
- 2015
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:11
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Tidskriftsartikel (refereegranskat)abstract
- Results of the first dust survey in JET with the ITER-Like Wall (JET-ILW) are presented. The sampling was performed using adhesive stickers from the divertor tiles where the greatest material deposition was detected after the first JET-ILW campaign in 2011-2012. The emphasis was especially on sampling and analysis of metal particles (Be and W) with the aim to determine the composition, size, surface topography and internal dust structure using a large set of methods: high-resolution scanning and transmission electron microscopy, focused ion beam, electron diffraction and also wavelength and energy dispersive x-ray spectroscopy. The most important was the identification of beryllium dust both in the form of flakes and droplets with dimensions in the micrometer range. Tungsten, molybdenum, inconel constituents were identified along with many impurity species. The particles are categorised and the origin of the various constituents discussed.
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| 9. |
- Bendor, Roy, et al.
(författare)
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Looking backward to the future: : On past-facing approaches to futuring
- 2021
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Ingår i: Futures. - : Elsevier. - 0016-3287 .- 1873-6378. ; 125
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Tidskriftsartikel (refereegranskat)abstract
- While the past is present in all futuring activities it tends to remain implicit and has not received adequate attention by futures scholars and practitioners. In response, this conceptual paper offers a novel framework with which the past can be brought into futures studies in a structured and comprehensive way. We begin by providing a brief account of how the past already figures in futures studies as part of efforts to understand the lingering effects of the past on the future; as part of a drive for ontological pluralization; and as a way to augment more mainstream futuring exercises. We then introduce two past-facing approaches to futuring, recasting and pastcasting, and illustrate their symmetry with the more familiar future-facing approaches, forecasting and backcasting. The symmetry, we argue, is based on shared aims and a shared style of inquiry. We then compare the different approaches and illustrate the landscape of futuring as an interplay of two dimensions: the focus of the activity on outcomes or pathways, and the stakes involved in it.
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| 10. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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