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1.
  • Pulit, S. L., et al. (författare)
  • Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
  • 2018
  • Ingår i: Neurology-Genetics. - 2376-7839. ; 4:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
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2.
  • Marini, Sandro, et al. (författare)
  • Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity A Meta-analysis
  • 2019
  • Ingår i: Jama Neurology. - 2168-6149. ; 76:4, s. 480-491
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. Objective: To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) ϵ4 alleles, the most potent genetic risk factor for ICH. Design, Setting, and Participants: This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. Main Outcomes and Measures: Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. Results: In total, 13124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE ϵ2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P
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3.
  • Abdo, A. A., et al. (författare)
  • Fermi Observations of High-Energy Gamma-Ray Emission from GRB 080916C
  • 2009
  • Ingår i: Science. - 0036-8075 .- 1095-9203. ; 323:5922, s. 1688-1693
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Gamma-ray bursts (GRBs) are highly energetic explosions signaling the death of massive stars in distant galaxies. The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gamma-ray energy. In September 2008, Fermi observed the exceptionally luminous GRB 080916C, with the largest apparent energy release yet measured. The high-energy gamma rays are observed to start later and persist longer than the lower energy photons. A simple spectral form fits the entire GRB spectrum, providing strong constraints on emission models. The known distance of the burst enables placing lower limits on the bulk Lorentz factor of the outflow and on the quantum gravity mass.</p>
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4.
  • Weiner, D. J., et al. (författare)
  • Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
  • 2017
  • Ingår i: Nature Genetics. - 1061-4036. ; 49:7, s. 978-
  • Tidskriftsartikel (refereegranskat)abstract
    • Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
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7.
  • Abdo, A. A., et al. (författare)
  • FERMI OBSERVATIONS OF GRB 090902B : A DISTINCT SPECTRAL COMPONENT IN THE PROMPT AND DELAYED EMISSION
  • 2009
  • Ingår i: Astrophysical Journal Letters. - 2041-8205. ; 706:1, s. L138-L144
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We report on the observation of the bright, long gamma-ray burst (GRB), GRB 090902B, by the Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) instruments on-board the Fermi observatory. This was one of the brightest GRBs to have been observed by the LAT, which detected several hundred photons during the prompt phase. With a redshift of z = 1.822, this burst is among the most luminous detected by Fermi. Time-resolved spectral analysis reveals a significant power-law component in the LAT data that is distinct from the usual Band model emission that is seen in the sub-MeV energy range. This power-law component appears to extrapolate from the GeV range to the lowest energies and is more intense than the Band component, both below similar to 50 keV and above 100 MeV. The Band component undergoes substantial spectral evolution over the entire course of the burst, while the photon index of the power-law component remains constant for most of the prompt phase, then hardens significantly toward the end. After the prompt phase, power-law emission persists in the LAT data as late as 1 ks post-trigger, with its flux declining as t(-1.5). The LAT detected a photon with the highest energy so far measured from a GRB, 33.4(-3.5)(+ 2.7) GeV. This event arrived 82 s after the GBM trigger and similar to 50 s after the prompt phase emission had ended in the GBM band. We discuss the implications of these results for models of GRB emission and for constraints on models of the extragalactic background light.</p>
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8.
  • Abdo, A. A., et al. (författare)
  • FERMI OBSERVATIONS OF GRB 090902B : A DISTINCT SPECTRAL COMPONENT IN THE PROMPT AND DELAYED EMISSION
  • 2009
  • Ingår i: Astrophysical Journal Letters. - 2041-8205. ; 706:1, s. L138-L144
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We report on the observation of the bright, long gamma-ray burst (GRB), GRB 090902B, by the Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) instruments on-board the Fermi observatory. This was one of the brightest GRBs to have been observed by the LAT, which detected several hundred photons during the prompt phase. With a redshift of z = 1.822, this burst is among the most luminous detected by Fermi. Time-resolved spectral analysis reveals a significant power-law component in the LAT data that is distinct from the usual Band model emission that is seen in the sub-MeV energy range. This power-law component appears to extrapolate from the GeV range to the lowest energies and is more intense than the Band component, both below similar to 50 keV and above 100 MeV. The Band component undergoes substantial spectral evolution over the entire course of the burst, while the photon index of the power-law component remains constant for most of the prompt phase, then hardens significantly toward the end. After the prompt phase, power-law emission persists in the LAT data as late as 1 ks post-trigger, with its flux declining as t(-1.5). The LAT detected a photon with the highest energy so far measured from a GRB, 33.4(-3.5)(+ 2.7) GeV. This event arrived 82 s after the GBM trigger and similar to 50 s after the prompt phase emission had ended in the GBM band. We discuss the implications of these results for models of GRB emission and for constraints on models of the extragalactic background light.</p>
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9.
  • Ackermann, M., et al. (författare)
  • Detection of a Spectral Break in the Extra Hard Component of GRB 090926A
  • 2011
  • Ingår i: Astrophysical Journal. - American Astronomical Society. - 0004-637X. ; 729:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the observation of the bright, long gamma-ray burst, GRB 090926A, by the Gamma-ray Burst Monitor and Large Area Telescope (LAT) instruments on board the Fermi Gamma-ray Space Telescope. GRB 090926A shares several features with other bright LAT bursts. In particular, it clearly shows a short spike in the light curve that is present in all detectors that see the burst, and this in turn suggests that there is a common region of emission across the entire Fermi energy range. In addition, while a separate high-energy power-law component has already been observed in other gamma-ray bursts, here we report for the first time the detection with good significance of a high-energy spectral break (or cutoff) in this power-law component around 1.4 GeV in the time-integrated spectrum. If the spectral break is caused by opacity to electron-positron pair production within the source, then this observation allows us to compute the bulk Lorentz factor for the outflow, rather than a lower limit.
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10.
  • Abdo, A. A., et al. (författare)
  • Fermi Observations of GRB 090902B : A Distinct Spectral Component in the Prompt and Delayed Emission
  • 2009
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. - 0004-637X ; 706:1, s. L138-L144
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We report on the observation of the bright, long gamma-ray burst (GRB), GRB 090902B, by the Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) instruments on-board the Fermi observatory. This was one of the brightest GRBs to have been observed by the LAT, which detected several hundred photons during the prompt phase. With a redshift of z = 1.822, this burst is among the most luminous detected by Fermi. Time-resolved spectral analysis reveals a significant power-law component in the LAT data that is distinct from the usual Band model emission that is seen in the sub-MeV energy range. This power-law component appears to extrapolate from the GeV range to the lowest energies and is more intense than the Band component, both below ~50 keV and above 100 MeV. The Band component undergoes substantial spectral evolution over the entire course of the burst, while the photon index of the power-law component remains constant for most of the prompt phase, then hardens significantly toward the end. After the prompt phase, power-law emission persists in the LAT data as late as 1 ks post-trigger, with its flux declining as t –1.5. The LAT detected a photon with the highest energy so far measured from a GRB, 33.4+2.7 –3.5 GeV. This event arrived 82 s after the GBM trigger and ~50 s after the prompt phase emission had ended in the GBM band. We discuss the implications of these results for models of GRB emission and for constraints on models of the extragalactic background light</p>
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