| 31. |
- Wang, Z., et al.
(author)
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Journal article (peer-reviewed)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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| 32. |
- Winkler, TW, et al.
(author)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Journal article (peer-reviewed)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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| 33. |
- Abdo, A. A., et al.
(author)
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FERMI/LARGE AREA TELESCOPE BRIGHT GAMMA-RAY SOURCE LIST
- 2009
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 183:1, s. 46-66
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Journal article (peer-reviewed)abstract
- Following its launch in 2008 June, the Fermi Gamma-ray Space Telescope (Fermi) began a sky survey in August. The Large Area Telescope (LAT) on Fermi in three months produced a deeper and better resolved map of the gamma-ray sky than any previous space mission. We present here initial results for energies above 100 MeV for the 205 most significant (statistical significance greater than similar to 10 sigma) gamma-ray sources in these data. These are the best characterized and best localized point-like (i.e., spatially unresolved) gamma-ray sources in the early mission data.
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| 34. |
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| 35. |
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| 36. |
- Abdo, A. A., et al.
(author)
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BRIGHT ACTIVE GALACTIC NUCLEI SOURCE LIST FROM THE FIRST THREE MONTHS OF THE FERMI LARGE AREA TELESCOPE ALL-SKY SURVEY
- 2009
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 700:1, s. 597-622
-
Journal article (peer-reviewed)abstract
- The first three months of sky-survey operation with the Large Area Telescope (LAT) onboard the Fermi Gamma-Ray Space Telescope reveal 132 bright sources at |b| > 10 degrees with test statistic greater than 100 ( corresponding to about 10 sigma). Two methods, based on the CGRaBS, CRATES, and BZCat catalogs, indicate high-confidence associations of 106 of these sources with known active galactic nuclei (AGNs). This sample is referred to as the LAT Bright AGN Sample (LBAS). It contains two radio galaxies, namely, Centaurus A and NGC 1275, and 104 blazars consisting of 58 flat spectrum radio quasars (FSRQs), 42 BL Lac objects, and 4 blazars with unknown classification. Four new blazars were discovered on the basis of the LAT detections. Remarkably, the LBAS includes 10 high-energy-peaked BL Lacs (HBLs), sources which were previously difficult to detect in the GeV range. Another 10 lower-confidence associations are found. Only 33 of the sources, plus two at |b| < 10 degrees, were previously detected with Energetic Gamma-Ray Experiment Telescope( EGRET), probably due to variability. The analysis of the gamma-ray properties of the LBAS sources reveals that the average GeV spectra of BL Lac objects are significantly harder than the spectra of FSRQs. No significant correlation between radio and peak gamma-ray fluxes is observed. Blazar log N-log S distributions and luminosity functions are constructed to investigate the evolution of the different blazar classes, with positive evolution indicated for FSRQs but none for BL Lacs. The contribution of LAT blazars to the total extragalactic gamma-ray intensity is estimated.
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| 37. |
- Hibar, Derrek P., et al.
(author)
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Novel genetic loci associated with hippocampal volume
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 38. |
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| 39. |
- Abdo, A. A., et al.
(author)
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Measurement of the Cosmic Ray e(+)+e(-) Spectrum from 20 GeV to 1 TeV with the Fermi Large Area Telescope
- 2009
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:Article number: 181101
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Journal article (peer-reviewed)abstract
- Designed as a high-sensitivity gamma-ray observatory, the Fermi Large Area Telescope is also an electron detector with a large acceptance exceeding 2 m(2) sr at 300 GeV. Building on the gamma-ray analysis, we have developed an efficient electron detection strategy which provides sufficient background rejection for measurement of the steeply falling electron spectrum up to 1 TeV. Our high precision data show that the electron spectrum falls with energy as E-3.0 and does not exhibit prominent spectral features. Interpretations in terms of a conventional diffusive model as well as a potential local extra component are briefly discussed.
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| 40. |
- Abdo, A. A., et al.
(author)
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EARLY FERMI GAMMA-RAY SPACE TELESCOPE OBSERVATIONS OF THE QUASAR 3C 454.3
- 2009
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 699:1, s. 817-823
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Journal article (peer-reviewed)abstract
- This is the first report of Fermi Gamma-Ray Space Telescope observations of the quasar 3C 454.3, which has been undergoing pronounced long-term outbursts since 2000. The data from the Large Area Telescope, covering 2008 July 7-October 6, indicate strong, highly variable.-ray emission with an average flux of similar to 3 x 10 (6) photons cm(-2) s(-1), for energies > 100 MeV. The gamma-ray flux is variable, with strong, distinct, symmetrically shaped flares for which the flux increases by a factor of several on a timescale of about 3 days. This variability indicates a compact emission region, and the requirement that the source is optically thin to pair production implies relativistic beaming with Doppler factor delta > 8, consistent with the values inferred from Very Long Baseline Interferometry observations of superluminal expansion (delta similar to 25). The observed gamma-ray spectrum is not consistent with a simple power law, but instead steepens strongly above similar to 2 GeV, and is well described by a broken power law with photon indices of similar to 2.3 and similar to 3.5 below and above the break, respectively. This is the first direct observation of a break in the spectrum of a high-luminosity blazar above 100 MeV, and it is likely direct evidence for an intrinsic break in the energy distribution of the radiating particles. Alternatively, the spectral softening above 2 GeV could be due to gamma-ray absorption via photon-photon pair production on the soft X-ray photon field of the host active galactic nucleus, but such an interpretation would require the dissipation region to be located very close (less than or similar to 100 gravitational radii) to the black hole, which would be inconsistent with the X-ray spectrum of the source.
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