| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 3. |
- Cornelis, Marilyn C, et al.
(författare)
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Targeted proteomic analysis of habitual coffee consumption
- 2018
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 283:2, s. 200-211
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health.OBJECTIVE: We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n=816) and followed-up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n=635) and EpiHealth (n=2418).METHODS: In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records while a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay.RESULTS: Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR<5%, P<2.31×10(-3) ): leptin (LEP), chitinase-3-like protein 1 (CHI3L), Tumor necrosis factor (TNF) receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (β, -0.042 SD per cup of coffee, P=0.028) and EpiHealth (β, -0.025 SD per time of coffee, P=0.004). The negative coffee-CHI3L association replicated in EpiHealth (β, -0.07, P=1.15×10(-7) ), but not in ULSAM (β, -0.034, P=0.16).CONCLUSIONS: The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee.
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| 4. |
- Abdollahi, S., et al.
(författare)
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Incremental Fermi Large Area Telescope Fourth Source Catalog
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 260:2
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Tidskriftsartikel (refereegranskat)abstract
- We present an incremental version (4FGL-DR3, for Data Release 3) of the fourth Fermi Large Area Telescope (LAT) catalog of γ-ray sources. Based on the first 12 years of science data in the energy range from 50 MeV to 1 TeV, it contains 6658 sources. The analysis improves on that used for the 4FGL catalog over eight years of data: more sources are fit with curved spectra, we introduce a more robust spectral parameterization for pulsars, and we extend the spectral points to 1 TeV. The spectral parameters, spectral energy distributions, and associations are updated for all sources. Light curves are rebuilt for all sources with 1 yr intervals (not 2 month intervals). Among the 5064 original 4FGL sources, 16 were deleted, 112 are formally below the detection threshold over 12 yr (but are kept in the list), while 74 are newly associated, 10 have an improved association, and seven associations were withdrawn. Pulsars are split explicitly between young and millisecond pulsars. Pulsars and binaries newly detected in LAT sources, as well as more than 100 newly classified blazars, are reported. We add three extended sources and 1607 new point sources, mostly just above the detection threshold, among which eight are considered identified, and 699 have a plausible counterpart at other wavelengths. We discuss the degree-scale residuals to the global sky model and clusters of soft unassociated point sources close to the Galactic plane, which are possibly related to limitations of the interstellar emission model and missing extended sources.
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| 5. |
- Abdollahi, S., et al.
(författare)
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Search for New Cosmic-Ray Acceleration Sites within the 4FGL Catalog Galactic Plane Sources
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 933:2
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Tidskriftsartikel (refereegranskat)abstract
- Cosmic rays are mostly composed of protons accelerated to relativistic speeds. When those protons encounter interstellar material, they produce neutral pions, which in turn decay into gamma-rays. This offers a compelling way to identify the acceleration sites of protons. A characteristic hadronic spectrum, with a low-energy break around 200 MeV, was detected in the gamma-ray spectra of four supernova remnants (SNRs), IC 443, W44, W49B, and W51C, with the Fermi Large Area Telescope. This detection provided direct evidence that cosmic-ray protons are (re-)accelerated in SNRs. Here, we present a comprehensive search for low-energy spectral breaks among 311 4FGL catalog sources located within 5° from the Galactic plane. Using 8 yr of data from the Fermi Large Area Telescope between 50 MeV and 1 GeV, we find and present the spectral characteristics of 56 sources with a spectral break confirmed by a thorough study of systematic uncertainty. Our population of sources includes 13 SNRs for which the proton–proton interaction is enhanced by the dense target material; the high-mass gamma-ray binary LS I+61 303; the colliding wind binary η Carinae; and the Cygnus star-forming region. This analysis better constrains the origin of the gamma-ray emission and enlarges our view to potential new cosmic-ray acceleration sites.
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| 6. |
- Ajello, M., et al.
(författare)
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A gamma-ray pulsar timing array constrains the nanohertz gravitational wave background
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 376:6592, s. 521-523
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Tidskriftsartikel (refereegranskat)abstract
- After large galaxies merge, their central supermassive black holes are expected to form binary systems. Their orbital motion should generate a gravitational wave background (GWB) at nanohertz frequencies. Searches for this background use pulsar timing arrays, which perform long-term monitoring of millisecond pulsars at radio wavelengths. We used 12.5 years of Fermi Large Area Telescope data to form a gamma-ray pulsar timing array. Results from 35 bright gamma-ray pulsars place a 95% credible limit on the GWB characteristic strain of 1.0 x 10(-14) at a frequency of 1 year(-1). The sensitivity is expected to scale with t(obs), the observing time span, as t(obs)(-13/6). This direct measurement provides an independent probe of the GWB while offering a check on radio noise models.
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| 7. |
- Ajello, M., et al.
(författare)
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Fermi Large Area Telescope Performance after 10 Years of Operation
- 2021
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 256:1
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Tidskriftsartikel (refereegranskat)abstract
- The Large Area Telescope (LAT), the primary instrument for the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view, high-energy gamma-ray telescope, covering the energy range from 30 MeV to more than 300 GeV. We describe the performance of the instrument at the 10 yr milestone. LAT performance remains well within the specifications defined during the planning phase, validating the design choices and supporting the compelling case to extend the duration of the Fermi mission. The details provided here will be useful when designing the next generation of high-energy gamma-ray observatories.
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| 8. |
- Alatalo, Tarja, 1961-, et al.
(författare)
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Characteristics of Teacher Competence : Trends over Time and Between Student Groups in the Swedish Compulsory School
- 2018
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Konferensbidrag (refereegranskat)abstract
- BackgroundAchievement differences across schools have increased in Sweden during the past two decades, at the same time as average achievement levels have declined, for example in mathematics (Holmlund et al., 2014; SOU 2014:05) and reading (Skolverket, 2013). These negative trends may be related to schools’ demographic, organizational and resource prerequisites. The organizational basis for the Swedish compulsory school has undergone significant changes since the late 1980s, with free school choice, an increasing number of private schools and a larger autonomy for school leaders. The increased school segregation with respect to migration background since the implementation of these reforms (Yang Hansen & Gustafsson, 2016), could possibly be caused by the continuing decline in inclusion of migrant students and a related educational inequality in instructional quality and teacher competence. Inclusion is defined as a structure of organizing integration according to particular rules and regulations.The results of research on effects of teacher competence are, however, somewhat fragmented and unclear, at least with respect to effects on different student groups. This can partly be explained by uncertainties in the determination of crucial teacher characteristics. Making comparisons between for example authorized and unauthorized teachers has been shown to be problematic. There is vast research in this field which is characterized by severe methodological problems, e.g. with respect to drawing causal conclusions from cross-sectional observational data. For example, no correlation between student achievement and various resource factors has been found in some studies (e.g. Hanushek, 1997), whereas others found a positive correlation (e.g. Greenwald, Hedges & Laine, 1996).A teacher effect on student achievement is, however, well manifested (e.g., Gustafsson, 2003; Gustafsson & Myrberg, 2002; Johansson, Myrberg, & Rosén, 2015; Nye, Konstantopoulus, & Hedges, 2004; Rockoff, 2004), and the results also suggest that lower achieving students, as for example immigrants, are the more likely to benefit from increases in teacher effectiveness (e.g., Sanders, 1998). Teacher quality is, furthermore, one of the resource factors that explains most of the increase in performance differences between schools in Sweden (Björklund, Fredriksson, Gustafsson, & Öckert, 2010, Ch 7; Gustafsson & Myrberg, 2002). The general reduction in teacher quality in Sweden the last decades (SOU 2014:05), and the decreased equality of allocation of teacher competence between schools (Hansson & Gustafsson, 2016; OECD, 2013), supports these results. However, the variation between student outcomes that different teachers are achieving (Hanushek, 2003) needs to be further problematized and discussed. Teacher knowledge and skills, teacher training and teaching experience are examples of characteristics highlighted in different meta-studies (e.g., Greenwald, Hedges & Laine, 1996), that should be subject of such an investigation.This study intends to develop a precise and differentiated description of teacher quality for use in future analyses of relations between teacher competence and educational results, with focus on interactions with student composition of schools due to students’ socio-economic and migration backgrounds. The description is among other factors focusing on teacher’s basic knowledge, subject-related and pedagogical training, and type of teacher training program. One aim is to investigate the variation over time in access to qualified teachers and the variation in teacher qualifications between schools. In further analyses, the significance of the teacher characteristics for literacy and mathematics in grades 1 to 6 will be focused.Overall, the project, which this study is a part of, is expected to generate insights about essential conditions for effective and equitable teaching in Swedish and mathematics in primary school, and about distributions of teacher competence across schools with different student composition.
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| 9. |
- Arking, D. E., et al.
(författare)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 10. |
- Baldini, L., et al.
(författare)
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Catalog of Long-term Transient Sources in the First 10 yr of Fermi-LAT Data
- 2021
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 256:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the first Fermi Large Area Telescope (LAT) catalog of long-term gamma-ray transient sources (1FLT). This comprises sources that were detected on monthly time intervals during the first decade of Fermi-LAT operations. The monthly timescale allows us to identify transient and variable sources that were not yet reported in other Fermi-LAT catalogs. The monthly data sets were analyzed using a wavelet-based source detection algorithm that provided the candidate new transient sources. The search was limited to the extragalactic regions of the sky to avoid the dominance of the Galactic diffuse emission at low Galactic latitudes. The transient candidates were then analyzed using the standard Fermi-LAT maximum likelihood analysis method. All sources detected with a statistical significance above 4 sigma in at least one monthly bin were listed in the final catalog. The 1FLT catalog contains 142 transient gamma-ray sources that are not included in the 4FGL-DR2 catalog. Many of these sources (102) have been confidently associated with active galactic nuclei (AGNs): 24 are associated with flat-spectrum radio quasars, 1 with a BL Lac object, 70 with blazars of uncertain type, 3 with radio galaxies, 1 with a compact steep-spectrum radio source, 1 with a steep-spectrum radio quasar, and 2 with AGNs of other types. The remaining 40 sources have no candidate counterparts at other wavelengths. The median gamma-ray spectral index of the 1FLT-AGN sources is softer than that reported in the latest Fermi-LAT AGN general catalog. This result is consistent with the hypothesis that detection of the softest gamma-ray emitters is less efficient when the data are integrated over year-long intervals.
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