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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 4. |
- Matuozzo, D, et al.
(författare)
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Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
- 2022
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants wasTLR7, with an OR of 27.68 (95%CI:1.5-528.7,P=1.1×10−4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2],P=2.1×10−4). Adding the recently reportedTYK2COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4];P=3.4×10−3). When these 14 loci andTLR7were considered, all individuals hemizygous (n=20) or homozygous (n=5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0],P=4.7×10−7), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9],P=0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years;P=1.68×10−5).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
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| 6. |
- Butler-Laporte, G, et al.
(författare)
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Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative
- 2022
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 18:11, s. e1010367-
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Tidskriftsartikel (refereegranskat)abstract
- Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.
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| 7. |
- Rouillard, Alexandra, et al.
(författare)
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Evidence for extreme floods in arid subtropical northwest Australia during the Little Ice Age chronozone (CE 1400-1850)
- 2016
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Ingår i: Quaternary Science Reviews. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0277-3791 .- 1873-457X. ; 144, s. 107-122
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a similar to 2000-year sediment sequence from the Fortescue Marsh (Martuyitha) in the eastern Pilbara region, which we have used to investigate changing hydroclimatic conditions in the arid subtropics of northwest Australia. The Pilbara is located at the intersection of the tropical Indian and Pacific Oceans and its modern rainfall regime is strongly influenced by tropical cyclones, the Intertropical Convergence Zone (ITCZ) and the Indo-Pacific Warm Pool. We identified four distinct periods within the record. The most recent period (P1: CE similar to 1990-present) reveals hydroclimatic conditions over recent decades that are the most persistently wet of potentially the last similar to 2000 years. During the previous centuries (P2: similar to CE 1600-1990), the Fortescue Marsh was overall drier but likely punctuated by a number of extreme floods, which are defined here as extraordinary, strongly episodic floods in drylands generated by rainfall events of high volume and intensity. The occurrence of extreme floods during this period, which encompasses the Little Ice Age (LIA; CE 1400-1850), is coherent with other southern tropical datasets along the ITCZ over the last 2000 years, suggesting synchronous hydroclimatic changes across the region. This extreme flood period was preceded by several hundred years (P3: similar to CE 700-1600) of less vigorous but more regular flows. The earliest period of the sediment record (P4: similar to CE 100-700) was the most arid, with sedimentary and preservation processes driven by prolonged drought. Our results highlight the importance of developing paleoclimate records from the tropical and sub-tropical arid zone, providing a long-term baseline of hydrological conditions in areas with limited historical observations. (C) 2016 Elsevier Ltd. All rights reserved.
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| 8. |
- Evaldsson, Martin, 1977-, et al.
(författare)
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Spin Splitting in open quantum dots
- 2005
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Ingår i: International Conference on the Physics of Semiconductors,2004. - Melville, New York : American Institute of Physics. ; , s. 1413-
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Konferensbidrag (refereegranskat)
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| 9. |
- Evaldsson, Martin, et al.
(författare)
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Spin splitting in open quantum dots
- 2004
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Ingår i: Europhysics letters. - : IOP Publishing. - 0295-5075 .- 1286-4854. ; 68:2, s. 261-267
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that the magnetoconductance of small lateral quantum dots in the strongly coupled regime (i.e. when the leads can support one or more propagating modes) shows a pronounced splitting of the conductance peaks and dips which persists over a wide range of magnetic fields (from zero field to the edge-state regime) and is virtually independent of the magnetic field strength. Our numerical analysis of the conductance based on the Hubbard Hamiltonian demonstrates that this is essentially a many-body/spin effect that can be traced to a splitting of degenerate levels in the corresponding closed dot. The above effect in open dots can be regarded as a counterpart of the Coulomb-blockade effect in weakly coupled dots, with the difference, however, that the splitting of the peaks originates from interactions between electrons of opposite spin.
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| 10. |
- Matuozzo, Daniela, et al.
(författare)
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Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
- 2023
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Ingår i: Genome medicine. - 1756-994X. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in~80% of cases.We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1×10-4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1×10-4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4×10-3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7×10-8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68×10-5).Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60years old.
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