| 891. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 892. |
- Stolk, Lisette, et al.
(författare)
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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
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Tidskriftsartikel (refereegranskat)abstract
- To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
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| 893. |
- Abdollahi, S., et al.
(författare)
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The Second Catalog of Flaring Gamma-Ray Sources from the Fermi All-sky Variability Analysis
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 846:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the second catalog of flaring gamma-ray sources (2FAV) detected with the Fermi All-sky Variability Analysis (FAVA), a tool that blindly searches for transients over the entire sky observed by the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. With respect to the first FAVA catalog, this catalog benefits from a larger data set, the latest LAT data release (Pass 8), as well as from an improved analysis that includes likelihood techniques for a more precise localization of the transients. Applying this analysis to the first 7.4 years of Fermi observations, and in two separate energy bands 0.1-0.8 GeV and 0.8-300 GeV, a total of 4547 flares were detected with significance greater than 6s (before trials), on the timescale of one week. Through spatial clustering of these flares, 518 variable gamma-ray sources were identified. Based on positional coincidence, likely counterparts have been found for 441 sources, mostly among the blazar class of active galactic nuclei. For 77 2FAV sources, no likely gamma-ray counterpart has been found. For each source in the catalog, we provide the time, location, and spectrum of each flaring episode. Studying the spectra of the flares, we observe a harder-when-brighter behavior for flares associated with blazars, with the exception of BL Lac flares detected in the low-energy band. The photon indexes of the flares are never significantly smaller than 1.5. For a leptonic model, and under the assumption of isotropy, this limit suggests that the spectrum of freshly accelerated electrons is never harder than p similar to 2.
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| 894. |
- Ackermann, M., et al.
(författare)
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MULTIWAVELENGTH EVIDENCE FOR QUASI-PERIODIC MODULATION IN THE GAMMA-RAY BLAZAR PG 1553+113
- 2015
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Ingår i: Astrophysical Journal Letters. - : Institute of Physics (IOP). - 2041-8205 .- 2041-8213. ; 813:2
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Tidskriftsartikel (refereegranskat)abstract
- We report for the first time a gamma-ray and multiwavelength nearly periodic oscillation in an active galactic nucleus. Using the Fermi Large Area Telescope we have discovered an apparent quasi-periodicity in the gamma-ray flux (E > 100 MeV) from the GeV/TeV BL Lac object PG 1553+113. The marginal significance of the 2.18 +/- 0.08 year period gamma-ray cycle is strengthened by correlated oscillations observed in radio and optical fluxes, through data collected in the Owens Valley Radio Observatory, Tuorla, Katzman Automatic Imaging Telescope, and Catalina Sky Survey monitoring programs and Swift-UVOT. The optical cycle appearing in similar to 10 years of data has a similar period, while the 15 GHz oscillation is less regular than seen in the other bands. Further long-term multiwavelength monitoring of this blazar may discriminate among the possible explanations for this quasi-periodicity.
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| 895. |
- Ackermann, M., et al.
(författare)
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SEARCH FOR DARK MATTER SATELLITES USING FERMI-LAT
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 747:2, s. 121-
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Tidskriftsartikel (refereegranskat)abstract
- Numerical simulations based on the ACDM model of cosmology predict a large number of as yet unobserved Galactic dark matter satellites. We report the results of a Large Area Telescope (LAT) search for these satellites via the gamma-ray emission expected from the annihilation of weakly interacting massive particle (WIMP) dark matter. Some dark matter satellites are expected to have hard gamma-ray spectra, finite angular extents, and a lack of counterparts at other wavelengths. We sought to identify LAT sources with these characteristics, focusing on gamma-ray spectra consistent with WIMP annihilation through the b (b) over bar channel. We found no viable dark matter satellite candidates using one year of data, and we present a framework for interpreting this result in the context of numerical simulations to constrain the velocity-averaged annihilation cross section for a conventional 100 GeV WIMP annihilating through the b (b) over bar channel.
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| 896. |
- Ackermann, M., et al.
(författare)
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Search for Gamma-Ray Emission from Local Primordial Black Holes with the Fermi Large Area Telescope
- 2018
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 857:1
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Tidskriftsartikel (refereegranskat)abstract
- Black holes with masses below approximately 10(15) g are expected to emit gamma-rays with energies above a few tens of MeV, which can be detected by the Fermi Large Area Telescope (LAT). Although black holes with these masses cannot be formed as a result of stellar evolution, they may have formed in the early universe and are therefore called primordial black holes (PBHs). Previous searches for PBHs have focused on either short-timescale bursts or the contribution of PBHs to the isotropic gamma-ray emission. We show that, in cases of individual PBHs, the Fermi-LAT is most sensitive to PBHs with temperatures above approximately 16 GeV and masses 6 x 10(11) g, which it can detect out to a distance of about 0.03 pc. These PBHs have a remaining lifetime of months to years at the start of the Fermi mission. They would appear as potentially moving point sources with gamma-ray emission that become spectrally harder and brighter with time until the PBH completely evaporates. In this paper, we develop a new algorithm to detect the proper motion of gamma-ray point sources, and apply it to 318 unassociated point sources at a high galactic latitude in the third Fermi-LAT source catalog. None of the unassociated point sources with spectra consistent with PBH evaporation show significant proper motion. Using the nondetection of PBH candidates, we derive a 99% confidence limit on the PBH evaporation rate in the vicinity of Earth, <(rho)over dot>(PBH) < 7.2 x 10(3) pc(-3) yr(-1). This limit is similar to the limits obtained with ground-based gamma-ray observatories.
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| 897. |
- Adcox, K, et al.
(författare)
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Net charge fluctuations in Au+Au interactions root s(NN)=130 GeV
- 2002
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Ingår i: Physical Review Letters. - 1079-7114. ; 89
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Tidskriftsartikel (refereegranskat)abstract
- Data from Au+ Au interactions at s(NN)=130 GeV, obtained with the PHENIX detector at the Relativistic Heavy-Ion Collider, are used to investigate local net charge fluctuations among particles produced near midrapidity. According to recent suggestions, such fluctuations may carry information from the quark-gluon plasma. This analysis shows that the fluctuations are dominated by a stochastic distribution of particles, but are also sensitive to other effects, like global charge conservation and resonance decays.
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| 898. |
- Ajello, M., et al.
(författare)
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FERMI LARGE AREA TELESCOPE OBSERVATIONS OF THE SUPERNOVA REMNANT G8.7-0.1
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 744:1, s. 80-
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Tidskriftsartikel (refereegranskat)abstract
- We present a detailed analysis of the GeV gamma-ray emission toward the supernova remnant (SNR) G8.7-0.1 with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. An investigation of the relationship between G8.7-0.1 and the TeV unidentified source HESS J1804-216 provides us with an important clue on diffusion process of cosmic rays if particle acceleration operates in the SNR. The GeV gamma-ray emission is extended with most of the emission in positional coincidence with the SNR G8.7-0.1 and a lesser part located outside the western boundary of G8.7-0.1. The region of the gamma-ray emission overlaps spatially connected molecular clouds, implying a physical connection for the gamma-ray structure. The total gamma-ray spectrum measured with LAT from 200 MeV-100 GeV can be described by a broken power-law function with a break of 2.4 +/- 0.6 (stat) +/- 1.2 (sys) GeV, and photon indices of 2.10 +/- 0.06 (stat) +/- 0.10 (sys) below the break and 2.70 +/- 0.12 (stat) +/- 0.14 (sys) above the break. Given the spatial association among the gamma rays, the radio emission of G8.7-0.1, and the molecular clouds, the decay of pi(0)s produced by particles accelerated in the SNR and hitting the molecular clouds naturally explains the GeV gamma-ray spectrum. We also find that the GeV morphology is not well represented by the TeV emission from HESS J1804-216 and that the spectrum in the GeV band is not consistent with the extrapolation of the TeV gamma-ray spectrum. The spectral index of the TeV emission is consistent with the particle spectral index predicted by a theory that assumes energy-dependent diffusion of particles accelerated in an SNR. We discuss the possibility that the TeV spectrum originates from the interaction of particles accelerated in G8.7-0.1 with molecular clouds, and we constrain the diffusion coefficient of the particles.
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| 899. |
- Allafort, A., et al.
(författare)
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PSR J2021+4026 IN THE GAMMA CYGNI REGION : THE FIRST VARIABLE gamma-RAY PULSAR SEEN BY THE Fermi LAT
- 2013
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Ingår i: ASTROPHYS J LETT. - 2041-8205. ; 777:1, s. L2-
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Tidskriftsartikel (refereegranskat)abstract
- Long-term monitoring of PSR J2021+4026 in the heart of the Cygnus region with the Fermi Large Area Telescope unveiled a sudden decrease in flux above 100 MeV over a timescale shorter than a week. The jump was near MJD 55850 (2011 October 16), with the flux decreasing from (8.33+/-0.08) x 10(-10) erg cm(-2) s(-1) to (6.86+/-0.13) x 10(-10) erg cm(-2) s(-1). Simultaneously, the frequency spindown rate increased from (7.8 +/- 0.1) x 10(-13) Hz s(-1) to (8.1 +/- 0.1) x 10(-13) Hz s(-1). Significant (>5 sigma) changes in the pulse profile and marginal (<3 sigma) changes in the emission spectrum occurred at the same time. There is also evidence for a small, steady flux increase over the 3 yr preceding MJD 55850. This is the first observation at gamma-ray energies of mode changes and intermittent behavior, observed at radio wavelengths for other pulsars. We argue that the change in pulsed gamma-ray emission is due to a change in emission beaming and we speculate that it is precipitated by a shift in the magnetic field structure, leading to a change of either effective magnetic inclination or effective current.
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| 900. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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