| 1. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 2. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 3. |
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| 4. |
- Boll, Rebecca, et al.
(författare)
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Imaging molecular structure through femtosecond photoelectron diffraction on aligned and oriented gas-phase molecules
- 2014
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Ingår i: Faraday Discussions. - : Royal Society of Chemistry (RSC). - 1364-5498. ; 171, s. 57-80
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Tidskriftsartikel (refereegranskat)abstract
- This paper gives an account of our progress towards performing femtosecond time-resolved photoelectron diffraction on gas-phase molecules in a pump-probe setup combining optical lasers and an X-ray free-electron laser. We present results of two experiments aimed at measuring photoelectron angular distributions of laser-aligned 1-ethynyl-4-fluorobenzene (C8H5F) and dissociating, laser-aligned 1,4-dibromobenzene (C6H4Br2) molecules and discuss them in the larger context of photoelectron diffraction on gas-phase molecules. We also show how the strong nanosecond laser pulse used for adiabatically laser-aligning the molecules influences the measured electron and ion spectra and angular distributions, and discuss how this may affect the outcome of future time-resolved photoelectron diffraction experiments.
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| 5. |
- Callaghan, Terry, et al.
(författare)
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Multi-Decadal Changes in Tundra Environments and Ecosystems : Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF)
- 2011
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 40:6, s. 705-716
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the responses of tundra systemsto global change has global implications. Most tundraregions lack sustained environmental monitoring and oneof the only ways to document multi-decadal change is toresample historic research sites. The International PolarYear (IPY) provided a unique opportunity for such researchthrough the Back to the Future (BTF) project (IPY project#512). This article synthesizes the results from 13 paperswithin this Ambio Special Issue. Abiotic changes includeglacial recession in the Altai Mountains, Russia; increasedsnow depth and hardness, permafrost warming, andincreased growing season length in sub-arctic Sweden;drying of ponds in Greenland; increased nutrient availabilityin Alaskan tundra ponds, and warming at mostlocations studied. Biotic changes ranged from relativelyminor plant community change at two sites in Greenland tomoderate change in the Yukon, and to dramatic increasesin shrub and tree density on Herschel Island, and in subarcticSweden. The population of geese tripled at one sitein northeast Greenland where biomass in non-grazed plotsdoubled. A model parameterized using results from a BTFstudy forecasts substantial declines in all snowbeds andincreases in shrub tundra on Niwot Ridge, Colorado overthe next century. In general, results support and provideimproved capacities for validating experimental manipulation,remote sensing, and modeling studies.
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| 6. |
- Carlsson, Pernilla, et al.
(författare)
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Polychlorinated biphenyls (PCBs) as sentinels for the elucidation of Arctic environmental change processes : a comprehensive review combined with ArcRisk project results
- 2018
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Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 25:23, s. 22499-22528
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Forskningsöversikt (refereegranskat)abstract
- Polychlorinated biphenyls (PCBs) can be used as chemical sentinels for the assessment of anthropogenic influences on Arctic environmental change. We present an overview of studies on PCBs in the Arctic and combine these with the findings from ArcRisk-a major European Union-funded project aimed at examining the effects of climate change on the transport of contaminants to and their behaviour of in the Arctic-to provide a case study on the behaviour and impact of PCBs over time in the Arctic. PCBs in the Arctic have shown declining trends in the environment over the last few decades. Atmospheric long-range transport from secondary and primary sources is the major input of PCBs to the Arctic region. Modelling of the atmospheric PCB composition and behaviour showed some increases in environmental concentrations in a warmer Arctic, but the general decline in PCB levels is still the most prominent feature. 'Within-Arctic' processing of PCBs will be affected by climate change-related processes such as changing wet deposition. These in turn will influence biological exposure and uptake of PCBs. The pan-Arctic rivers draining large Arctic/sub-Arctic catchments provide a significant source of PCBs to the Arctic Ocean, although changes in hydrology/sediment transport combined with a changing marine environment remain areas of uncertainty with regard to PCB fate. Indirect effects of climate change on human exposure, such as a changing diet will influence and possibly reduce PCB exposure for indigenous peoples. Body burdens of PCBs have declined since the 1980s and are predicted to decline further.
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| 7. |
- Christensen, JS, et al.
(författare)
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Diffusion of phosphorus in relaxed Si1-xGex films and strained Si/Si1-xGex heterostructures
- 2003
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 94:10, s. 6533-6540
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorus diffusion has been studied in relaxed Si1-xGex samples (x=0.11 and 0.19) and strained Si/Si1-xGex/Si heterostructures (x=0.08, 0.13, and 0.18). The diffusivity of P is found to increase with increasing Ge content, while the influence of compressive strain results in a decrease in diffusivity as compared to that in relaxed material. The effect of strain is found to be equivalent to an apparent activation energy of -13 eV per unit strain, where the negative sign indicates that the P diffusion is mediated by interstitials in Si1-xGex (x<0.20). This conclusion is also supported by an experiment utilizing injection of Si self-interstitials, which results in an enhanced P diffusion in strained Si1-xGex. Further, P is found to segregate into Si across Si/Si1-xGex interfaces and the segregation coefficient increases with increasing Ge concentration.
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| 8. |
- Christensen, JS, et al.
(författare)
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Phosphorus and boron diffusion in silicon under equilibrium conditions
- 2003
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 82:14, s. 2254-2256
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Tidskriftsartikel (refereegranskat)abstract
- The intrinsic diffusion of phosphorus and boron in high-purity epitaxial silicon films has been studied. Phosphorus diffusion in a wide temperature range (810 to 1100 degreesC) revealed diffusion coefficients with an Arrhenius behavior exhibiting an activation energy of 2.74+/-0.07 eV and a pre-exponential factor of (8+/-5)x10(-4) cm(2)/s. In the temperature range of 810 to 1050 degreesC, boron was found to diffuse with an activation energy of 3.12+/-0.04 eV and a pre-exponential factor of 0.06+/-0.02 cm(2)/s. These results differ from those of many previous studies, but this deviation may to a large extent be attributed to slow transients before equilibrium concentrations of point defects are established at temperatures below similar to1000 degreesC. Despite a similar diffusion mechanism mediated by Si self-interstitials, P exhibits a lower activation energy than B because of stronger bonding to the Si self-interstitial.
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| 9. |
- Christensen, J. S., et al.
(författare)
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Phosphorus diffusion in the presence of threading dislocations in strain relaxed SiGe films
- 2006
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Ingår i: Materials Science in Semiconductor Processing. - : Elsevier BV. - 1369-8001 .- 1873-4081. ; 9:4-5, s. 650-654
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Tidskriftsartikel (refereegranskat)abstract
- We have studied phosphorus diffusion in strain relaxed Si1-xGex films (x = 0.1 and 0.2) by secondary ion mass spectrometry (SIMS). The relaxed films were grown with low-pressure chemical vapor deposition (LPCVD) on a Si substrate followed by a graded SiGe layer. Two sets of samples were prepared under different growth conditions, and by transmission electron microscopy (TEM) it was shown that these conditions resulted in one set of samples containing a high density of threading dislocations in the relaxed films, and one set with a low dislocation density. The SIMS profiles of the phosphorus distributions in the samples, after annealing in N-2-ambient in the temperature range of 700-950 degrees C, show that the phosphorus diffusion is significantly faster in the films with the high dislocation density. Furthermore, the data suggests that the fast diffusion is due to a higher mobility of the diffusing complex rather than an increase in the point defect concentration mediating the diffusion, a result which indicates that the threading dislocations may act as channels for the rapid dopant diffusion in SiGe.
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| 10. |
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