| 1. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 2. |
- de Rojas, I., et al.
(author)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)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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| 3. |
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| 4. |
- Bellenguez, C, et al.
(author)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Journal article (peer-reviewed)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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| 5. |
- Arndt, D. S., et al.
(author)
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STATE OF THE CLIMATE IN 2017
- 2018
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In: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Research review (peer-reviewed)
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| 6. |
- Clark, DW, et al.
(author)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Journal article (peer-reviewed)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 7. |
- Aartsen, M. G., et al.
(author)
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Multipole analysis of IceCube data to search for dark matter accumulated in the Galactic halo
- 2015
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In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 75:1
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Journal article (peer-reviewed)abstract
- Dark matter which is bound in the Galactic halo might self-annihilate and produce a flux of stable final state particles, e. g. high energy neutrinos. These neutrinos can be detected with IceCube, a cubic-kilometer sized Cherenkov detector. Given IceCube's large field of view, a characteristic anisotropy of the additional neutrino flux is expected. In this paper we describe a multipole method to search for such a large-scale anisotropy in IceCube data. This method uses the expansion coefficients of a multipole expansion of neutrino arrival directions and incorporates signal-specific weights for each expansion coefficient. We apply the technique to a high-purity muon neutrino sample from the Northern Hemisphere. The final result is compatible with the null-hypothesis. As no signal was observed, we present limits on the self-annihilation cross-section averaged over the relative velocity distribution down to 1.9x10(-23) cm(3) s(-1) for a dark matter particle mass of 700-1,000 GeV and direct annihilation into nu(nu) over bar. The resulting exclusion limits come close to exclusion limits from gamma-ray experiments, that focus on the outer Galactic halo, for high dark matter masses of a few TeV and hard annihilation channels.
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| 8. |
- Aartsen, M. G., et al.
(author)
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Observation of High-Energy Astrophysical Neutrinos in Three Years of IceCube Data
- 2014
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 113:10, s. 101101-
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Journal article (peer-reviewed)abstract
- A search for high-energy neutrinos interacting within the IceCube detector between 2010 and 2012 provided the first evidence for a high-energy neutrino flux of extraterrestrial origin. Results from an analysis using the same methods with a third year (2012-2013) of data from the complete IceCube detector are consistent with the previously reported astrophysical flux in the 100 TeV-PeV range at the level of 10(-8) GeV cm(-2) s(-1) sr(-1) per flavor and reject a purely atmospheric explanation for the combined three-year data at 5.7 sigma. The data are consistent with expectations for equal fluxes of all three neutrino flavors and with isotropic arrival directions, suggesting either numerous or spatially extended sources. The three-year data set, with a live time of 988 days, contains a total of 37 neutrino candidate events with deposited energies ranging from 30 to 2000 TeV. The 2000-TeV event is the highest-energy neutrino interaction ever observed.
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| 9. |
- Aartsen, M. G., et al.
(author)
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SEARCHES FOR EXTENDED AND POINT-LIKE NEUTRINO SOURCES WITH FOUR YEARS OF ICECUBE DATA
- 2014
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 796:2, s. 109-
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Journal article (peer-reviewed)abstract
- We present results on searches for point-like sources of neutrinos using four years of IceCube data, including the first year of data from the completed 86 string detector. The total livetime of the combined data set is 1373 days. For an E-2 spectrum, the observed 90% C. L. flux upper limits are similar to 10(-12) TeV-1 cm(-2) s(-1) for energies between 1 TeV and 1 PeV in the northern sky and similar to 10(-11) TeV-1 cm(-2) s(-1) for energies between 100 TeV and 100 PeV in the southern sky. This represents a 40% improvement compared to previous publications, resulting from both the additional year of data and the introduction of improved reconstructions. In addition, we present the first results from an all-sky search for extended sources of neutrinos. We update the results of searches for neutrino emission from stacked catalogs of sources and test five new catalogs; two of Galactic supernova remnants and three of active galactic nuclei. In all cases, the data are compatible with the background-only hypothesis, and upper limits on the flux of muon neutrinos are reported for the sources considered.
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| 10. |
- Aartsen, M. G., et al.
(author)
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Search for non-relativistic magnetic monopoles with IceCube
- 2014
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In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 74:7, s. 2938-
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Journal article (peer-reviewed)abstract
- The IceCube Neutrino Observatory is a large Cherenkov detector instrumenting of Antarctic ice. The detector can be used to search for signatures of particle physics beyond the Standard Model. Here, we describe the search for non-relativistic, magnetic monopoles as remnants of the Grand Unified Theory (GUT) era shortly after the Big Bang. Depending on the underlying gauge group these monopoles may catalyze the decay of nucleons via the Rubakov-Callan effect with a cross section suggested to be in the range of to . In IceCube, the Cherenkov light from nucleon decays along the monopole trajectory would produce a characteristic hit pattern. This paper presents the results of an analysis of first data taken from May 2011 until May 2012 with a dedicated slow-particle trigger for DeepCore, a subdetector of IceCube. A second analysis provides better sensitivity for the brightest non-relativistic monopoles using data taken from May 2009 until May 2010. In both analyses no monopole signal was observed. For catalysis cross sections of the flux of non-relativistic GUT monopoles is constrained up to a level of at a 90 % confidence level, which is three orders of magnitude below the Parker bound. The limits assume a dominant decay of the proton into a positron and a neutral pion. These results improve the current best experimental limits by one to two orders of magnitude, for a wide range of assumed speeds and catalysis cross sections.
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