11. |
- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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12. |
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13. |
- Wang, QBS, et al.
(författare)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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14. |
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15. |
- Abdo, A. A., et al.
(författare)
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FERMI DISCOVERY OF GAMMA-RAY EMISSION FROM NGC 1275
- 2009
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 699:1, s. 31-39
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of high-energy (E > 100 MeV) gamma-ray emission from NGC 1275, a giant elliptical galaxy lying at the center of the Perseus cluster of galaxies, based on observations made with the Large Area Telescope (LAT) of the Fermi Gamma-ray Space Telescope. The positional center of the gamma-ray source is only approximate to 3' away from the NGC 1275 nucleus, well within the 95% LAT error circle of approximate to 5'. The spatial distribution of gamma-ay photons is consistent with a point source. The average flux and power-law photon index measured with the LAT from 2008 August 4 to 2008 December 5 are F-gamma = (2.10 +/- 0.23) x 10(-7) ph (>100 MeV) cm(-2) s(-1) and Gamma = 2.17 +/- 0.05, respectively. The measurements are statistically consistent with constant flux during the four-month LAT observing period. Previous EGRET observations gave an upper limit of F-gamma < 3.72 x 10(-8) ph (>100 MeV) cm(-2) s(-1) to the gamma-ray flux from NGC 1275. This indicates that the source is variable on timescales of years to decades, and therefore restricts the fraction of emission that can be produced in extended regions of the galaxy cluster. Contemporaneous and historical radio observations are also reported. The broadband spectrum of NGC 1275 is modeled with a simple one-zone synchrotron/synchrotron self-Compton model and a model with a decelerating jet flow.
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16. |
- 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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17. |
- Abdo, A. A., et al.
(författare)
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The Fermi Gamma-Ray Space Telescope Discovers the Pulsar in the Young Galactic Supernova Remnant CTA 1
- 2008
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 322:5905, s. 1218-1221
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Tidskriftsartikel (refereegranskat)abstract
- Energetic young pulsars and expanding blast waves [ supernova remnants (SNRs)] are the most visible remains after massive stars, ending their lives, explode in core-collapse supernovae. The Fermi Gamma- Ray Space Telescope has unveiled a radio quiet pulsar located near the center of the compact synchrotron nebula inside the supernova remnant CTA 1. The pulsar, discovered through its gamma- ray pulsations, has a period of 316.86 milliseconds and a period derivative of 3.614 x 10(-13) seconds per second. Its characteristic age of 10(4) years is comparable to that estimated for the SNR. We speculate that most unidentified Galactic gamma- ray sources associated with star- forming regions and SNRs are such young pulsars.
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18. |
- Abdo, A. A., et al.
(författare)
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DETECTION OF THE ENERGETIC PULSAR PSR B1509-58 AND ITS PULSAR WIND NEBULA IN MSH 15-52 USING THE FERMI-LARGE AREA TELESCOPE
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 714:1, s. 927-936
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Tidskriftsartikel (refereegranskat)abstract
- We report the detection of high-energy gamma-ray emission from the young and energetic pulsar PSR B1509-58 and its pulsar wind nebula (PWN) in the composite supernova remnant G320.4-1.2 (aka MSH 15-52). Using 1 yr of survey data with the Fermi-Large Area Telescope (LAT), we detected pulsations from PSR B1509-58 up to 1 GeV and extended gamma-ray emission above 1 GeV spatially coincident with the PWN. The pulsar light curve presents two peaks offset from the radio peak by phases 0.96 +/- 0.01 and 0.33 +/- 0.02. New constraining upper limits on the pulsar emission are derived below 1 GeV and confirm a severe spectral break at a few tens of MeV. The nebular spectrum in the 1-100 GeV energy range is well described by a power law with a spectral index of (1.57 +/- 0.17 +/- 0.13) and a flux above 1 GeV of (2.91 +/- 0.79 +/- 1.35) x 10(-9) cm(-2) s(-1). The first errors represent the statistical errors on the fit parameters, while the second ones are the systematic uncertainties. The LAT spectrum of the nebula connects nicely with Cherenkov observations, and indicates a spectral break between GeV and TeV energies.
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19. |
- Abdo, A. A., et al.
(författare)
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Fermi large area telescope observations of PSR J1836+5925
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 712:2, s. 1209-1218
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of the gamma-ray pulsar PSR J1836+5925, powering the formerly unidentified EGRET source 3EG J1835+5918, was one of the early accomplishments of the Fermi Large Area Telescope (LAT). Sitting 25 degrees off the Galactic plane, PSR J1836+5925 is a 173 ms pulsar with a characteristic age of 1.8 million years, a spindown luminosity of 1.1 x 10(34) erg s(-1), and a large off-peak (OP) emission component, making it quite unusual among the known gamma-ray pulsar population. We present an analysis of one year of LAT data, including an updated timing solution, detailed spectral results, and a long-term light curve showing no indication of variability. No evidence for a surrounding pulsar wind nebula is seen and the spectral characteristics of the OP emission indicate it is likely magnetospheric. Analysis of recent XMM-Newton observations of the X-ray counterpart yields a detailed characterization of its spectrum, which, like Geminga, is consistent with that of a neutron star showing evidence for both magnetospheric and thermal emission.
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20. |
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