| 11. |
- Zeggini, Eleftheria, et al.
(författare)
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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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| 12. |
- Apatenkov, S. V., et al.
(författare)
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Conjugate observation of sharp dynamical boundary in the inner magnetosphere by Cluster and DMSP spacecraft and ground network
- 2008
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Ingår i: Annales Geophysicae. - 0992-7689 .- 1432-0576. ; 26:9, s. 2771-2780
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Tidskriftsartikel (refereegranskat)abstract
- We investigate an unusual sharp boundary separating two plasma populations (inner magnetospheric plasma with high fluxes of energetic particles and plasma sheet) observed by the Cluster quartet near its perigee on 16 December 2003. Cluster was in a pearl-on-string configuration at 05:00 MLT and mapped along magnetic field lines to similar to 8-9 R-E in the equatorial plane. It was conjugate to the MIRACLE network and the DMSP F16 spacecraft passed close to Cluster footpoint. The properties of the sharp boundary, repeatedly crossed 7 times by five spacecraft during similar to 10 min, are: (1) upward FAC sheet at the boundary with similar to 30 nA/m(2) current density at Cluster and similar to 2000 nA/m(2) at DMSP; (2) the boundary had an embedded layered structure with different thickness scales, the electron population transition was at similar to 20 km scale at Cluster (<7 km at DMSP), proton population had a scale similar to 100 km, while the FAC sheet thickness was estimated to be similar to 500 km at Cluster (similar to 100 km at DMSP); (3) the boundary propagated in the earthward-eastward direction at similar to 8 km/s in situ (equatorward-eastward similar to 0.8 km/s in ionosphere), and then decelerated and/or stopped. We discuss the boundary formation by the collision of two different plasmas which may include dynamical three-dimensional field-aligned current loops.
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| 13. |
- de Bakker, Paul I. W., et al.
(författare)
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Transferability of tag SNPs in genetic association studies in multiple populations
- 2006
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 38:11, s. 1298-1303
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Tidskriftsartikel (refereegranskat)abstract
- A general question for linkage disequilibrium-based association studies is how power to detect an association is compromised when tag SNPs are chosen from data in one population sample and then deployed in another sample. Specifically, it is important to know how well tags picked from the HapMap DNA samples capture the variation in other samples. To address this, we collected dense data uniformly across the four HapMap population samples and eleven other population samples. We picked tag SNPs using genotype data we collected in the HapMap samples and then evaluated the effective coverage of these tags in comparison to the entire set of common variants observed in the other samples. We simulated case-control association studies in the non-HapMap samples under a disease model of modest risk, and we observed little loss in power. These results demonstrate that the HapMap DNA samples can be used to select tags for genome-wide association studies in many samples around the world.
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| 14. |
- Saxena, Richa, et al.
(författare)
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Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5829, s. 1331-1336
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Tidskriftsartikel (refereegranskat)abstract
- New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
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| 15. |
- Yamauchi, M., et al.
(författare)
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Magnetospheric solitary structure maintained by 3000 km/s ions as a cause of westward moving auroral bulge at 19 MLT
- 2009
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 27:7, s. 2947-2969
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Tidskriftsartikel (refereegranskat)abstract
- In the evening equatorial magnetosphere at about 4 R-E geocentric distance and 19 MLT, the four Cluster spacecraft observed a solitary structure with a width of about 1000 similar to 2000 km in the propagation direction. The solitary structure propagates sunward with about 5 similar to 10 km/s carrying sunward electric field (in the propagation direction) of up to about 10 mV/m (total potential drop of about 5 similar to 10 kV), depletion of magnetic field of about 25%, and a duskward E x B convection up to 50 km/s of He+ rich cold plasma without O+. At the same time, auroral images from the IMAGE satellite together with ground based geomagnetic field data showed a westward (sunward at this location) propagating auroral bulge at the magnetically conjugate ionosphere with the solitary structure. The solitary structure is maintained by flux enhancement of selectively 3000 km/s ions (about 50 keV for H+, 200 keV for He+, and 750 keV for O+). These ions are the main carrier of the diamagnetic current causing the magnetic depletion, whereas the polarization is maintained by different behavior of energetic ions and electrons. Corresponding to aurora, field-aligned accelerated ionospheric plasma of several keV appeared at Cluster from both hemispheres simultaneously. Together with good correspondence in location and propagation velocity between the auroral bulge and the solitary structure, this indicates that the sunward moving auroral bulge is caused by the sunward propagation of the solitary structure which is maintained by energetic ions. The solitary structure might also be the cause of Pi2-like magnetic variation that started simultaneously at Cluster location.
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