| 1. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 2. |
- 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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| 3. |
- Keleta, S, et al.
(författare)
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Exclusive measurement of two-pion production in the dd -> He-4 pi pi reaction
- 2009
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Ingår i: Nuclear Physics A. - : Elsevier BV. - 0375-9474 .- 1873-1554. ; 825:1-2, s. 71-90
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Tidskriftsartikel (refereegranskat)abstract
- The results from the first kinematically complete measurement of the dd -> He-4 pi pi reaction are reported. The aim was to investigate a long standing puzzle regarding the origin of the peculiar pi pi-invariant mass distributions appearing in double pion production in light ion collisions, the so-called ABC effect. The measurements were performed at the incident deuteron energies of 712 MeV and 1029 MeV. with the WASA detector assembly at CELSIUS in Uppsala, Sweden. We report the observation of a characteristic enhancement at low pi pi-invariant mass at 712 MeV, the lowest energy yet. At the higher energy, in addition to confirming previous experimental observations, Our results reveal a strong angular dependence of the pions in the overall centre of mass system. The results are qualitatively reproduced by a theoretical model, according to which the ABC effect is described as resulting from a kinematical enhancement in the production of the pion pairs from two parallel and independent NN -> d pi sub-processes. (C) 2009 Elsevier B.V. All rights reserved.
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| 4. |
- Bashkanov, M., et al.
(författare)
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Double-Pionic Fusion of Nuclear Systems and the "ABC" Effect : Approaching a Puzzle by Exclusive and Kinematically Complete Measurements
- 2009
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:5, s. 052301-
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Tidskriftsartikel (refereegranskat)abstract
- The ABC effect-a puzzling low-mass enhancement in the pi pi invariant mass spectrum, first observed by Abashian, Booth, and Crowe-is well known from inclusive measurements of two-pion production in nuclear fusion reactions. Here we report on the first exclusive and kinematically complete measurements of the most basic double-pionic fusion reaction pn -> d pi(0)pi(0) at beam energies of 1.03 and 1.35 GeV. The measurements, which have been carried out at CELSIUS-WASA, reveal the ABC effect to be a (pi pi)(I=L=0) channel phenomenon associated with both a resonancelike energy dependence in the integral cross section and the formation of a Delta Delta system in the intermediate state. A corresponding simple s-channel resonance ansatz provides a surprisingly good description of the data.
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| 5. |
- Berlowski, M., et al.
(författare)
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Measurement of eta meson decays into lepton-antilepton pairs
- 2008
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Ingår i: Physical Review D. Particles and fields. - : American Physical Society. - 0556-2821 .- 1089-4918. ; 77:3, s. 032004-
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Tidskriftsartikel (refereegranskat)abstract
- A search for rare lepton decays of the eta meson was performed using the WASA detector at CELSIUS. Two candidates for double Dalitz decay eta -> e(+)e(-)e(+)e(-) events are reported with a background of 1.3 +/- 0.2 events. This allows to set an upper limit to the branching ratio of 9.7x10(-5) (90% CL). The branching ratio for the decay eta -> e(+)e(-)gamma is determined to (7.8 +/- 0.5(stat)+/- 0.8(syst))x10(-3) in agreement with world average value. An upper limit (90% CL) for the branching ratio for the eta -> e(+)e(-) decay is 2.7x10(-5) and a limit for the sum of the eta ->mu(+)mu(-)mu(+)mu(-) and eta ->pi(+)pi(-)mu(+)mu(-) decays is 3.6x10(-4).
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| 6. |
- Schonning, K., et al.
(författare)
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The pd -> He-3 eta pi(0) reaction at T-p=1450 MeV CELSIUS/WASA Collaboration
- 2010
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 685:1, s. 33-37
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Tidskriftsartikel (refereegranskat)abstract
- The cross section for the pd -> He-3 eta pi(0) reaction has been measured at a beam energy of 1450 MeV using the WASA detector at the CELSIUS storage ring. The He-3 was detected in coincidence with four photons from the decays of the two mesons. The data indicate that the production mechanism involves the formation of the Delta(1232) isobar. Although the beam energy does not allow the full peak of this resonance to be seen, the invariant mass distributions Of all three pairs of final particles are well reproduced by a phase space Monte Carlo simulation weighted with the p-wave factor of the square of the pi(0) momentum in the He-3 pi(0) system.
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| 7. |
- Bashkanov, M., et al.
(författare)
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Exclusive measurements of pd -> He-3 pi pi : The ABC effect revisited
- 2006
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 637:4-5, s. 223-228
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Tidskriftsartikel (refereegranskat)abstract
- Exclusive measurements of the reactions pd -> He-3 pi(+)7 pi(-) and pd -> He-3 pi(0)pi(0) have been carried out at T-p = 0.893 GeV at the CELSIUS storage ring using the WASA detector. The pi(+)pi(-) channel evidences a pronounced enhancement at low invariant pi pi masses-as anticipated from previous inclusive measurements of the ABC effect. This enhancement is seen to be even much larger in the isoscalar pi(0)pi(0) channel. The differential distributions prove this enhancement to be of scalar-isoscalar nature. Delta Delta calculations give a good description of the data, if a boundstate condition is imposed for the intermediate Delta Delta system.
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| 8. |
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| 9. |
- Kren, F., et al.
(författare)
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THE pp -> d pi(+)pi(0) REACTION - A CASE OF Delta Delta EXCITATION WITHOUT ABC-EFFECT
- 2009
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Ingår i: International Journal of Modern Physics A. - 0217-751X .- 1793-656X. ; 24:2-3, s. 561-563
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Tidskriftsartikel (refereegranskat)abstract
- The ABC effect, a low-mass enhancement in the invariant pp mass, is observed in double-pionic fusion reactions leading to a bound nuclear system in the final state. From previous measurements there have been indications that this phenomenon is resctricted to the sigma channel of the pp system. With exclusive measurements of the pp -> d pi(+)pi(0) reaction at T-p = 1.1 GeV we demonstrate that, indeed, the ABC effect does not occur in the vector-isovector Delta Delta channel (rho channel) despite the fact that the Delta Delta excitation is oberved to be the dominant reaction process. We also show that this reaction is well described by a t-channel Delta Delta excitation with the subsequent decay into the vector-isovector Delta Delta channel given by the rho channel operator.
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| 10. |
- Pettersson, Henrik, et al.
(författare)
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eta PRODUCTION IN PROTON-PROTON COLLISIONS AT 72 MeV EXCESS ENERGY
- 2009
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Ingår i: International Journal of Modern Physics A. - 0217-751X .- 1793-656X. ; 24:2-3, s. 446-449
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Tidskriftsartikel (refereegranskat)abstract
- The production of eta mesons at an excess energy of 72 MeV has been studied in the reaction pp -> pp(eta)gamma gamma. It is shown that a simple model with Pp. final states included reproduces observed differential distributions better than the same model restricted to Ss, Sd and Ds final states. The strong influence of the Pp states could be taken as an indication of rho dominance within an one boson exchange model for the excitation of N*(1535).
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