| 1. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 2. |
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| 3. |
- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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| 4. |
- Olalde, I., et al.
(författare)
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The Beaker phenomenon and the genomic transformation of northwest Europe
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 555:7695, s. 190-196
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Tidskriftsartikel (refereegranskat)abstract
- From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.
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| 5. |
- Snodgrass, C., et al.
(författare)
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The 67P/Churyumov-Gerasimenko observation campaign in support of the Rosetta mission
- 2017
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Ingår i: Philosophical Transactions. Series A. - : The Royal Society. - 1364-503X .- 1471-2962. ; 375:2097
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Tidskriftsartikel (refereegranskat)abstract
- We present a summary of the campaign of remote observations that supported the European Space Agency's Rosetta mission. Telescopes across the globe (and in space) followed comet 67P/ Churyumov-Gerasimenko from before Rosetta's arrival until nearly the end of the mission in September 2016. These provided essential data for mission planning, large-scale context information for the coma and tails beyond the spacecraft and a way to directly compare 67P with other comets. The observations revealed 67P to be a relatively 'well-behaved' comet, typical of Jupiter family comets and with activity patterns that repeat from orbit to orbit. Comparison between this large collection of telescopic observations and the in situ results from Rosetta will allow us to better understand comet coma chemistry and structure. This work is just beginning as the mission ends-in this paper, we present a summary of the ground-based observations and early results, and point to many questions that will be addressed in future studies. This article is part of the themed issue 'Cometary science after Rosetta'.
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| 6. |
- Wessel, Jennifer, et al.
(författare)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 7. |
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| 8. |
- Gicquel, A., et al.
(författare)
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Modelling of the outburst on 2015 July 29 observed with OSIRIS cameras in the Southern hemisphere of comet 67P/Churyumov-Gerasimenko
- 2017
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Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 469, s. S178-S185
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Tidskriftsartikel (refereegranskat)abstract
- Images of the nucleus and the coma (gas and dust) of comet 67P/Churyumov-Gerasimenko have been acquired by the OSIRIS (Optical, Spectroscopic and Infrared Remote Imaging System) cameras since 2014 March using both the wide-angle camera and the narrow-angle camera (NAC). We use images from the NAC camera to study a bright outburst observed in the Southern hemisphere on 2015 July 29. The high spatial resolution of the NAC is needed to localize the source point of the outburst on the surface of the nucleus. The heliocentric distance is 1.25 au and the spacecraft-comet distance is 186 km. Aiming to better understand the physics that led to the outgassing, we used the Direct Simulation Monte Carlo method to study the gas flow close to the nucleus and the dust trajectories. The goal is to understand the mechanisms producing the outburst. We reproduce the opening angle of the outburst in the model and constrain the outgassing ratio between the outburst source and the local region. The outburst is in fact a combination of both gas and dust, in which the active surface is approximately 10 times more active than the average rate found in the surrounding areas. We need a number of dust particles 7.83 x 10(11) to 6.90 x 10(15) (radius 1.97-185 mu m), which correspond to a mass of dust (220-21) x 10(3) kg.
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| 9. |
- Fornasier, S., et al.
(författare)
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Rosetta's comet 67P/Churyumov-Gerasimenko sheds its dusty mantle to reveal its icy nature
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 354:6319, s. 1566-1570
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Tidskriftsartikel (refereegranskat)abstract
- The Rosetta spacecraft has investigated comet 67P/Churyumov-Gerasimenko from large heliocentric distances to its perihelion passage and beyond. We trace the seasonal and diurnal evolution of the colors of the 67P nucleus, finding changes driven by sublimation and recondensation of water ice. The whole nucleus became relatively bluer near perihelion, as increasing activity removed the surface dust, implying that water ice is widespread underneath the surface. We identified large (1500 square meters) ice-rich patches appearing and then vanishing in about 10 days, indicating small-scale heterogeneities on the nucleus. Thin frosts sublimating in a few minutes are observed close to receding shadows, and rapid variations in color are seen on extended areas close to the terminator. These cyclic processes are widespread and lead to continuously, slightly varying surface properties.
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| 10. |
- Gicquel, A., et al.
(författare)
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Sublimation of icy aggregates in the coma of comet 67P/Churyumov-Gerasimenko detected with the OSIRIS cameras on board Rosetta
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 462, s. S57-S66
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Tidskriftsartikel (refereegranskat)abstract
- Beginning in 2014 March, the OSIRIS (Optical, Spectroscopic, and Infrared Remote Imaging System) cameras began capturing images of the nucleus and coma (gas and dust) of comet 67P/Churyumov-Gerasimenko using both the wide angle camera (WAC) and the narrow angle camera (NAC). The many observations taken since July of 2014 have been used to study the morphology, location, and temporal variation of the comet's dust jets. We analysed the dust monitoring observations shortly after the southern vernal equinox on 2015 May 30 and 31 with the WAC at the heliocentric distance R-h = 1.53 AU, where it is possible to observe that the jet rotates with the nucleus. We found that the decline of brightness as a function of the distance of the jet is much steeper than the background coma, which is a first indication of sublimation. We adapted a model of sublimation of icy aggregates and studied the effect as a function of the physical properties of the aggregates (composition and size). The major finding of this paper was that through the sublimation of the aggregates of dirty grains (radius a between 5 and 50 mu m) we were able to completely reproduce the radial brightness profile of a jet beyond 4 km from the nucleus. To reproduce the data, we needed to inject a number of aggregates between 8.5 x 10(13) and 8.5 x 10(10) for a = 5 and 50 mu m, respectively, or an initial mass of H2O ice around 22 kg.
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