| 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. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Kane, Gordon, et al.
(författare)
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Deriving the inflaton in compactified M-theory with a de Sitter vacuum
- 2019
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 100:6
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Tidskriftsartikel (refereegranskat)abstract
- Compactifying M-theory on a manifold of G2 holonomy gives a UV complete 4D theory. It is supersymmetric, with soft supersymmetry breaking via gaugino condensation that simultaneously stabilizes all moduli and generates a hierarchy between the Planck and the Fermi scale. It generically has gauge matter, chiral fermions, and several other important features of our world. Here we show that the theory also contains a successful inflaton, which is a linear combination of moduli closely aligned with the overall volume modulus of the compactified G2 manifold. The scheme does not rely on ad hoc assumptions, but derives from an effective quantum theory of gravity. Inflation arises near an inflection point in the potential which can be deformed into a local minimum. This implies that a de Sitter vacuum can occur in the moduli potential even without uplifting. Generically present charged hidden sector matter generates a de Sitter vacuum as well.
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| 5. |
- Mauritsen, Thorsten, et al.
(författare)
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Developments in the MPI-M Earth System Model version 1.2 (MPI-ESM1.2) and Its Response to Increasing CO2
- 2019
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Ingår i: Journal of Advances in Modeling Earth Systems. - 1942-2466. ; 11:4, s. 998-1038
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Tidskriftsartikel (refereegranskat)abstract
- A new release of the Max Planck Institute for Meteorology Earth System Model version 1.2 (MPI-ESM1.2) is presented. The development focused on correcting errors in and improving the physical processes representation, as well as improving the computational performance, versatility, and overall user friendliness. In addition to new radiation and aerosol parameterizations of the atmosphere, several relatively large, but partly compensating, coding errors in the model's cloud, convection, and turbulence parameterizations were corrected. The representation of land processes was refined by introducing a multilayer soil hydrology scheme, extending the land biogeochemistry to include the nitrogen cycle, replacing the soil and litter decomposition model and improving the representation of wildfires. The ocean biogeochemistry now represents cyanobacteria prognostically in order to capture the response of nitrogen fixation to changing climate conditions and further includes improved detritus settling and numerous other refinements. As something new, in addition to limiting drift and minimizing certain biases, the instrumental record warming was explicitly taken into account during the tuning process. To this end, a very high climate sensitivity of around 7 K caused by low-level clouds in the tropics as found in an intermediate model version was addressed, as it was not deemed possible to match observed warming otherwise. As a result, the model has a climate sensitivity to a doubling of CO2 over preindustrial conditions of 2.77 K, maintaining the previously identified highly nonlinear global mean response to increasing CO2 forcing, which nonetheless can be represented by a simple two-layer model.
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| 6. |
- Reinert, Annika, et al.
(författare)
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A precision search for WIMPs with charged cosmic rays
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : Institute of Physics Publishing (IOPP). - 1475-7516. ; :1
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Tidskriftsartikel (refereegranskat)abstract
- AMS-02 has reached the sensitivity to probe canonical thermal WIMPs by their annihilation into antiprotons. Due to the high precision of the data, uncertainties in the astrophysical background have become the most limiting factor for indirect dark matter detection. In this work we systematically quantify and where possible reduce uncertainties in the antiproton background. We constrain the propagation of charged cosmic rays through the combination of antiproton, BBC and positron data. Cross section uncertainties are determined from a wide collection of accelerator data and are for the first time ever fully taken into account. This allows us to robustly constrain even subdominant dark matter signals through their spectral properties. For a standard NFW dark matter profile we are able to exclude thermal WIMPs with masses up to 570 GeV which annihilate into bottom quarks. While we confirm a reported excess compatible with dark matter of mass around 80 GeV, its local (global) significance only reaches 2.2 sigma (1.1 sigma) in our analysis.
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| 7. |
- Winkler, Martin Wolfgang
(författare)
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Cosmic ray antiprotons at high energies
- 2017
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : Institute of Physics (IOP). - 1475-7516. ; :2
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Tidskriftsartikel (refereegranskat)abstract
- Cosmic ray antiprotons provide a powerful tool to probe dark matter annihilations in our galaxy. The sensitivity of this important channel is, however, diluted by sizable uncertainties in the secondary antiproton background. In this work, we improve the calculation of secondary antiproton production with a particular focus on the high energy regime. We employ the most recent collider data and identify a substantial increase of antiproton cross sections with energy. This increase is driven by the violation of Feynman scaling as well as by an enhanced strange hyperon production. The updated antiproton production cross sections are made publicly available for independent use in cosmic ray studies. In addition, we provide the correlation matrix of cross section uncertainties for the AMS-02 experiment. At high energies, the new cross sections improve the compatibility of the AMS-02 data with a pure secondary origin of antiprotons in cosmic rays.
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| 8. |
- Winkler, Martin Wolfgang
(författare)
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Decay and detection of a light scalar boson mixing with the Higgs boson
- 2019
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Ingår i: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 99:1
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Tidskriftsartikel (refereegranskat)abstract
- The simplest extension of the standard model consists in adding one singlet scalar field which mixes with the Higgs boson. O(GeV) masses of the new scalar carry strong motivation from relaxion, dark matter and inflation models. The decay of a GeV scalar is, however, notoriously difficult to address since, at this mass scale, the chiral expansion breaks down and perturbative QCD does not apply. Existing estimates of the GeV scalar decay rate disagree by several orders of magnitude. In this work, we perform a new dispersive analysis in order to strongly reduce these uncertainties and to address discrepancies in earlier results. We will update existing limits on light scalars and future experimental sensitivities which are in some cases strongly affected by the new-found decay rates. The meson form factors provided in this work, can be used to generalize our findings to non-universally coupled light scalars.
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| 9. |
- Zhang, Rong, et al.
(författare)
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ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 x 10(-08)). A meta-analysis of rs6874700 of our previous and present study showed a p value of 9.2 x 10(-19). Developmental biology models were used to clarify the location of ISL1 activity in the forming urinary tract. Genetic lineage analysis of Isl1-expressing cells by the lineage tracer mouse model showed Isl1-expressing cells in the urinary tract of mouse embryos at E10.5 and distributed in the bladder at E15.5. Expression of isl1 in zebrafish larvae staged 48 hpf was detected in a small region of the developing pronephros. Our study supports ISL1 as a major susceptibility gene for CBE and as a regulator of urinary tract development.
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