| 11. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 12. |
- Ip, H. F., et al.
(författare)
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Genetic association study of childhood aggression across raters, instruments, and age
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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| 13. |
- Abeysekara, A. U., et al.
(författare)
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VERITAS and Fermi-LAT Observations of TeV Gamma-Ray Sources Discovered by HAWC in the 2HWC Catalog
- 2018
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing. - 0004-637X .- 1538-4357. ; 866:1
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Tidskriftsartikel (refereegranskat)abstract
- The High Altitude Water Cherenkov (HAWC) collaboration recently published their 2HWC catalog, listing 39 very high energy (VHE; >100 GeV) gamma-ray sources based on 507 days of observation. Among these, 19 sources are not associated with previously known teraelectronvolt (TeV) gamma-ray sources. We have studied 14 of these sources without known counterparts with VERITAS and Fermi-LAT. VERITAS detected weak gamma-ray emission in the 1 TeV-30 TeV band in the region of DA 495, a pulsar wind nebula coinciding with 2HWC J1953+294, confirming the discovery of the source by HAWC. We did not find any counterpart for the selected 14 new HAWC sources from our analysis of Fermi-LAT data for energies higher than 10 GeV. During the search, we detected gigaelectronvolt (GeV) gamma-ray emission coincident with a known TeV pulsar wind nebula, SNR G54.1+0.3 (VER J1930+188), and a 2HWC source, 2HWC J1930+188. The fluxes for isolated, steady sources in the 2HWC catalog are generally in good agreement with those measured by imaging atmospheric Cherenkov telescopes. However, the VERITAS fluxes for SNR G54.1+0.3, DA 495, and TeV J2032+4130 are lower than those measured by HAWC, and several new HAWC sources are not detected by VERITAS. This is likely due to a change in spectral shape, source extension, or the influence of diffuse emission in the source region.
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| 14. |
- Abdo, A. A., et al.
(författare)
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The second Fermi large area telescope catalog of gamma-ray pulsars
- 2013
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 208:2, s. 17-
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Tidskriftsartikel (refereegranskat)abstract
- This catalog summarizes 117 high-confidence ≥0.1 GeV gamma-ray pulsar detections using three years of data acquired by the Large Area Telescope (LAT) on the Fermi satellite. Half are neutron stars discovered using LAT data through periodicity searches in gamma-ray and radio data around LAT unassociated source positions. The 117 pulsars are evenly divided into three groups: millisecond pulsars, young radio-loud pulsars, and young radio-quiet pulsars. We characterize the pulse profiles and energy spectra and derive luminosities when distance information exists. Spectral analysis of the off-peak phase intervals indicates probable pulsar wind nebula emission for four pulsars, and off-peak magnetospheric emission for several young and millisecond pulsars. We compare the gamma-ray properties with those in the radio, optical, and X-ray bands. We provide flux limits for pulsars with no observed gamma-ray emission, highlighting a small number of gamma-faint, radio-loud pulsars. The large, varied gamma-ray pulsar sample constrains emission models. Fermi's selection biases complement those of radio surveys, enhancing comparisons with predicted population distributions.
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| 15. |
- Acero, F., et al.
(författare)
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FERMI LARGE AREA TELESCOPE THIRD SOURCE CATALOG
- 2015
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 218:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the third Fermi Large Area Telescope (LAT) source catalog (3FGL) of sources in the 100 MeV-300 GeV range. Based on the first 4 yr of science data from the Fermi Gamma-ray Space Telescope mission, it is the deepest yet in this energy range. Relative to the Second Fermi LAT catalog, the 3FGL catalog incorporates twice as much data, as well as a number of analysis improvements, including improved calibrations at the event reconstruction level, an updated model for Galactic diffuse.-ray emission, a refined procedure for source detection, and improved methods for associating LAT sources with potential counterparts at other wavelengths. The 3FGL catalog includes 3033 sources above 4 sigma significance, with source location regions, spectral properties, and monthly light curves for each. Of these, 78 are flagged as potentially being due to imperfections in the model for Galactic diffuse emission. Twenty-five sources are modeled explicitly as spatially extended, and overall 238 sources are considered as identified based on angular extent or correlated variability (periodic or otherwise) observed at other wavelengths. For 1010 sources we have not found plausible counterparts at other wavelengths. More than 1100 of the identified or associated sources are active galaxies of the blazar class; several other classes of non-blazar active galaxies are also represented in the 3FGL. Pulsars represent the largest Galactic source class. From source counts of Galactic sources we estimate that the contribution of unresolved sources to the Galactic diffuse emission is similar to 3% at 1 GeV.
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| 16. |
- Ackermann, M., et al.
(författare)
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FERMI-LAT OBSERVATIONS OF THE LIGO EVENT GW150914
- 2016
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Ingår i: Astrophysical Journal Letters. - : Institute of Physics Publishing (IOPP). - 2041-8205 .- 2041-8213. ; 823:1
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Tidskriftsartikel (refereegranskat)abstract
- The Fermi Large Area Telescope (LAT) has an instantaneous field of view (FoV) covering similar to 1/5 of the sky and it completes a survey of the entire sky in high-energy gamma-rays every 3 hr. It enables searches for transient phenomena over timescales from milliseconds to years. Among these phenomena could be electromagnetic counterparts to gravitational wave (GW) sources. In this paper, we present a detailed study of the LAT observations relevant to Laser Interferometer Gravitational-wave Observatory (LIGO) event GW150914, which is the first direct detection of gravitational waves and has been interpreted as being due to the coalescence of two stellar-mass black holes. The localization region for GW150914 was outside the LAT FoV at the time of the GW signal. However, as part of routine survey observations, the LAT observed the entire LIGO localization region within similar to 70 minutes of the trigger and thus enabled a comprehensive search for a.-ray counterpart to GW150914. The study of the LAT data presented here did not find any potential counterparts to GW150914, but it did provide limits on the presence of a transient counterpart above 100 MeV on timescales of hours to days over the entire GW150914 localization region.
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| 17. |
- 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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| 18. |
- Ackermann, M., et al.
(författare)
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Fermi establishes classical novae as a distinct class of gamma-ray sources
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 345:6196, s. 554-558
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Tidskriftsartikel (refereegranskat)abstract
- A classical nova results from runaway thermonuclear explosions on the surface of a white dwarf that accretes matter from a low-mass main-sequence stellar companion. In 2012 and 2013, three novae were detected in gamma rays and stood in contrast to the first gamma-ray-detected nova V407 Cygni 2010, which belongs to a rare class of symbiotic binary systems. Despite likely differences in the compositions and masses of their white dwarf progenitors, the three classical novae are similarly characterized as soft-spectrum transient gamma-ray sources detected over 2- to 3-week durations. The gamma-ray detections point to unexpected high-energy particle acceleration processes linked to the mass ejection from thermonuclear explosions in an unanticipated class of Galactic gamma-ray sources.
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| 19. |
- Ackermann, M., et al.
(författare)
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THE THIRD CATALOG OF ACTIVE GALACTIC NUCLEI DETECTED BY THE FERMI LARGE AREA TELESCOPE
- 2015
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 810:1
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Tidskriftsartikel (refereegranskat)abstract
- The third catalog of active galactic nuclei (AGNs) detected by the Fermi-LAT (3LAC) is presented. It is based on the third Fermi-LAT catalog (3FGL) of sources detected between 100 MeV and 300 GeV with a Test Statistic greater than 25, between 2008 August 4 and 2012 July 31. The 3LAC includes 1591 AGNs located at high Galactic latitudes (vertical bar b vertical bar > 10 degrees), a 71% increase over the second catalog based on 2 years of data. There are 28 duplicate associations, thus 1563 of the 2192 high-latitude gamma-ray sources of the 3FGL catalog are AGNs. Most of them (98%) are blazars. About half of the newly detected blazars are of unknown type, i.e., they lack spectroscopic information of sufficient quality to determine the strength of their emission lines. Based on their gamma-ray spectral properties, these sources are evenly split between flat-spectrum radio quasars (FSRQs) and BL Lacs. The most abundant detected BL Lacs are of the high-synchrotron-peaked (HSP) type. About 50% of the BL Lacs have no measured redshifts. A few new rare outliers (HSP-FSRQs and high-luminosity HSP BL Lacs) are reported. The general properties of the 3LAC sample confirm previous findings from earlier catalogs. The fraction of 3LAC blazars in the total population of blazars listed in BZCAT remains non-negligible even at the faint ends of the BZCAT-blazar radio, optical, and X-ray flux distributions, which hints that even the faintest known blazars could eventually shine in gamma-rays at LAT-detection levels. The energy-flux distributions of the different blazar populations are in good agreement with extrapolation from earlier catalogs.
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| 20. |
- Abdollahi, S., et al.
(författare)
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Fermi Large Area Telescope Fourth Source Catalog
- 2020
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 247:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the fourth Fermi Large Area Telescope catalog (4FGL) of gamma-ray sources. Based on the first eight years of science data from the Fermi Gamma-ray Space Telescope mission in the energy range from 50 MeV to 1 TeV, it is the deepest yet in this energy range. Relative to the 3FGL catalog, the 4FGL catalog has twice as much exposure as well as a number of analysis improvements, including an updated model for the Galactic diffuse gamma-ray emission, and two sets of light curves (one-year and two-month intervals). The 4FGL catalog includes 5064 sources above 4 sigma significance, for which we provide localization and spectral properties. Seventy-five sources are modeled explicitly as spatially extended, and overall, 358 sources are considered as identified based on angular extent, periodicity, or correlated variability observed at other wavelengths. For 1336 sources, we have not found plausible counterparts at other wavelengths. More than 3130 of the identified or associated sources are active galaxies of the blazar class, and 239 are pulsars.
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