| 1. |
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| 2. |
- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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| 3. |
- Wightman, D. P., et al.
(författare)
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A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
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Tidskriftsartikel (refereegranskat)abstract
- Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
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| 4. |
- Elvsashagen, T, et al.
(författare)
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The genetic architecture of human brainstem structures and their involvement in common brain disorders
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4016-
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Tidskriftsartikel (refereegranskat)abstract
- Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson’s disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
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| 5. |
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| 6. |
- Kaufmann, Tobias, et al.
(författare)
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Common brain disorders are associated with heritable patterns of apparent aging of the brain
- 2019
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
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Tidskriftsartikel (refereegranskat)abstract
- Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
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| 7. |
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| 8. |
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| 9. |
- Jansen, Iris E, et al.
(författare)
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Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
- 2022
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Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 144:5, s. 821-842
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n=8074; replication n=5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
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| 10. |
- Khaydukov, Yu. N., et al.
(författare)
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Evidence for spin-triplet superconducting correlations in metal-oxide heterostructures with noncollinear magnetization
- 2014
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Ingår i: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969. ; 90:3, s. Article no. 035130 -
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Tidskriftsartikel (refereegranskat)abstract
- Heterostructures composed of ferromagnetic La0.7Sr0.3MnO3, ferromagnetic SrRuO3, and superconducting YBa2Cu3O6+x were studied experimentally. Structures of composition Au/La0.7Sr0.3MnO3/SrRuO3/YBa2Cu3O6+x were prepared by pulsed laser deposition, and their high quality was confirmed by x-ray diffraction and reflectometry. Anoncollinear magnetic state of the heterostructureswas revealed by means of superconducting quantum interference device magnetometry and polarized neutron reflectometry. We have further observed superconducting currents in mesa structures fabricated by deposition of a second superconducting Nb layer on top of the heterostructure, followed by patterning with photolithography and ion-beam etching. Josephson effects observed in these mesa structures can be explained by the penetration of a triplet component of the superconducting order parameter into the magnetic layers.
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| 11. |
- Kislinskiǐ, Yu V., et al.
(författare)
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Copper oxide superconducting/antiferromagnetic interface
- 2015
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Ingår i: Solid State Phenomena. - 1662-9779 .- 1012-0394. - 9783038354826 ; 233-234, s. 733-736
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Konferensbidrag (refereegranskat)abstract
- Superconducting Nb/Au/Ca1-xSrxCuO2/YBa2Cu3O7 mesa-heterostructures were investigated. Dependencies of electrical parameters versus inverse capacitance were measured. A band diagram which takes into account an accumulation of holes inCa1-xSrxCuO2 interlayer and band bending due to difference of work functions was proposed. The dependencies of electrical parameters were analyzed by examining the quasipartical and superconducting currents.
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| 12. |
- Ovsyannikov, Gennady, 1948, et al.
(författare)
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Proximity effect and electron transport in oxide hybrid heterostructures with superconducting/magnetic interfaces
- 2011
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Ingår i: Superconductor Science and Technology. - : IOP Publishing. - 0953-2048 .- 1361-6668. ; 24:5, s. Art. no. 055012-
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Tidskriftsartikel (refereegranskat)abstract
- We report on electron transport in oxide heterostructures with superconducting/magnetic (S/M) thin film interfaces. The investigated hybrid mesa-heterostructures consist of a cuprate superconductor, a nonsuperconducting cuprate (antiferromagnetic) or manganite (ferromagnetic) interlayer with thickness d(M) = 5-50 nm and a conventional superconductor (Nb). The superconducting critical current (I-C) with a critical current density j(c) = 10(3) A cm(-2) (for d(M) = 10 nm) and a characteristic voltage ICRN = 100-200 mu V (RN is normal resistance) are observed at liquid helium temperature for a CaXSr1-XCuO2 antiferromagnetic cuprate interlayer with a thickness of d(M) = 10-50 nm. The superconducting current-phase relation of heterostructures deviates from the regular sine type, demonstrating a second harmonic component. These hybrid heterostructures with S/M interfaces show unusually high sensitivity to external magnetic fields. When substituting the cuprate interlayer by a manganite film, no critical current was observed although the manganite interlayer was made several times thinner (down to d(M)
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Constantinian, K. Y., et al.
(författare)
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Electron transport and microwave dynamics of hybrid Nb/Au/CaSrCuO/YBaCuO planar Josephson junctions
- 2009
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 234:4, s. Art. no. 042004-
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Konferensbidrag (refereegranskat)abstract
- We report on measurements of dc electron transport and microwave dynamics of thin film hybrid Josephson junctions with an oxide antiferromagnetic interlayer. The base superconducting electrode YBaCuO and the antiferromagnetic (AF) interlayer CaSrCuO (with thickness d 20 - 70 nm) were grown by laser ablation on NdGaO3 substrates. I-V curves were well fitted to RSJ model and had no excess current, ICRN products were of order 0.2 mV at T=4.2 K. We did not observe any noticeable reduction of I CRN with increasing d. Such "tunnellike" behaviour also resulted in appearance of singularities on I-V curve when magnetic field was applied. Oscillating with microwave power integer and half-integer Shapiro steps were registered along with sub-harmonic detector response. Moreover, for some of junctions a "devil" staircase structure was observed on I-V curves and giant noise-like signals were measured in 1-2 GHz band at the certain levels of microwave power. Observed features, noise performance and the impact of the second harmonic in current-phase relation on junction dynamics are discussed taking into account data for structures without AF interlayer.
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| 18. |
- Constantinian, K. Y., et al.
(författare)
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Hybrid superconducting heterostructures with magnetic interlayers
- 2021
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Ingår i: Radioelektronika, Nanosistemy, Informacionnye Tehnologii. - : Editorial Board of Journal Radioelectronics, Nanosystems, Information Technology RENSIT. - 2218-3000 .- 2414-1267. ; 13:4, s. 471-478
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Tidskriftsartikel (refereegranskat)abstract
- Electron transport processes in oxide superconducting heterostructures with epitaxially grown magnetic thin-film interlayers, in which the interaction of superconducting correlations and magnetic ordering occurs due to superconducting and magnetic proximity effects, have been studied experimentally. Hybrid mesa-heterostructures were prepared from thin-film bottom cuprate superconductor (S), magnetic (M) interlayer made of manganite or an antiferromagnetic cuprate, and the upper electrode made from an ordinary superconductor. When the cuprate antiferromagnetic material was replaced by a ferromagnetic manganite interlayer, the superconducting current was suppressed, although the thin magnetic film was several times thinner, 5 nm, and the temperature was lowered to 0.3 K. At low temperatures dependences of differential resistance vs. voltage for mesa-heterostructures with manganite interlayer featured mini-gap low-energy states.
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| 19. |
- Constantinian, K. Y., et al.
(författare)
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Hybrid superconducting mesa-heterostructure with manganite-ruthenate interlayer
- 2014
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 507:Part 4, s. Art. no. 042007-
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Konferensbidrag (refereegranskat)abstract
- We present experimental data on Josephson effect in hybrid superconducting mesa-heterostructures (HSMH) with composite manganite-ruthenate interlayer. The HSMH base electrode consisted of the cuprate superconductor YBa 2Cu3O7 grown epitaxially on a NdGaO substrate using laser ablation. The interlayer was composed from in-situ deposited SrRuO3 (F1) and La0.7Sr0.3MnO3 (F2) thin films, each characterized by different directions of magnetization. The top electrode was Nb/Au thin film. A superconducting current was observed when the interlayer thickness was well above the correlation length, determined by the exchange field in F1 and F2. Obtained IC (H) dependences and non-sinusoidal current-phase relation evaluated from microwave measurements are discussed in terms of generation of long-range spin triplet superconducting current component in heterostructures with interfaces of singlet superconductors and bilayer ferromagnetic materials with different spatial directions of magnetization.
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| 20. |
- Constantinian, K. Y., et al.
(författare)
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Interfaces in superconducting hybrid heterostructures with an antiferromagnetic interlayer
- 2013
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Ingår i: Physics of the Solid State. - 1063-7834 .- 1090-6460. ; 55:3, s. 461-465
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Tidskriftsartikel (refereegranskat)abstract
- The structural, X-ray diffraction, and electrophysical studies of hybrid superconducting hetero-structures with an interlayer of cuprate antiferromagnetic Ca1 - x Sr (x) CuO2 (CSCO) with the upper electrode Nb/Au and the lower electrode Y(B)a(2)Cu(3)O(7 - delta) (YBCO) have been carried out. It has been experimentally shown that the epitaxial growth of two cuprates, YBCO and CSCO, results in the formation of an interface on which the enrichment of the CSCO interlayer with charge carriers proceeds to a depth of about 20 nm. In this case, the conduction of the enriched CSCO region proves to be closer to metallic, whereas the CSCO film deposited onto the NdGaO3 substrate is a Mott insulator with hopping conduction.
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| 21. |
- Constantinian, K. Y., et al.
(författare)
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Spin-Triplet Superconducting Current in Metal-Oxide Heterostructures With Composite Ferromagnetic Interlayer
- 2016
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Ingår i: IEEE Transactions on Applied Superconductivity. - : Institute of Electrical and Electronics Engineers (IEEE). - 1558-2515 .- 1051-8223. ; 26:3
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Tidskriftsartikel (refereegranskat)abstract
- Superconducting heterostructures fabricated from oxide superconductor YBa2Cu2O7-delta and a composite ferromagnet La0.7Sr0.3MnO3/SrRuO3 interlayer and Au/Nb counter electrode were studied experimentally. Superconducting current was observed at magnetic field H raised up to 2000 Oe, which is greater than saturation magnetic field of manganite La0.7Sr0.3MnO3 (of order 100 Oe) and greater by a few orders than the value of magnetic field corresponding to penetration of one magnetic flux quantum. Microwave measurements of integer and half-integer Shapiro steps in conditions when relatively low external magnetic fieldH < 30 Oe was applied showed that the second harmonic in the current-phase relation of superconducting current becomes as big as the first harmonic. Fourier analysis of I-C(H) dependence allows extracting the components of fractional periods in I-C(H) function that also confirms a deviation from the sinusoidal current-phase relation. The obtained experimental data are explained by theoretical models that predict a huge enhancement of the second harmonic of the spin-triplet component in the superconducting current. The current-phase relation could be controlled by an external magnetic field, changing the directions of magnetization in the composite bilayer ferromagnet, which is inserted between two spin-singlet superconductors.
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| 22. |
- Demidov, V. V., et al.
(författare)
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Magnetic anisotropy in strained manganite films and bicrystal junctions
- 2013
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 113:16
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Tidskriftsartikel (refereegranskat)abstract
- Transport and magnetic properties of La0.67Sr0.33MnO3 (LSMO) manganite thin films and bicrystal junctions were investigated. Epitaxial manganite films were grown on SrTiO3, LaAlO3, NdGaO3 (NGO), and (LaAlO3)(0.3) + (Sr2AlTaO6)(0.7) substrates, and their magnetic anisotropy were determined by two independent techniques of magnetic resonance spectroscopy. It was demonstrated that by using these techniques, a small (0.3%) anisotropy of crystal structure at the (110) surface plane of the orthorhombic NGO substrate leads to uniaxial magnetic anisotropy of the films in the plane of the substrate at least at the room temperature. It was found that on vicinal NGO substrates, the value of magnetic anisotropy strength can be varied in the range 100-200 Oe at T = 295 K by changing the substrate vicinal angle from 0 degrees to 25 degrees. Measurement of the magnetic anisotropy of manganite bicrystal junction demonstrated the presence of two ferromagnetic spin subsystems for both types of bicrystal boundaries with tilting of basal plane of manganite tilted bicrystal (TB-junction) and with rotation of crystallographic axes (RB-junction) used for comparison. The magnetoresistance of TB-junctions increases with decreasing temperature and the misorientation angle. Variation of bicrystal misorientation angle does not lead to change of misorientation of easy magnetic axes in the film parts forming TB-junction. Analysis of the voltage dependencies of bicrystal junction conductivity show that the low value of the magnetoresistance for the LSMO bicrystal junctions can be caused by two scattering mechanisms. The first one is the spin-flip of spin-polarized carriers due to the strong electron-electron interactions in a disordered layer at the bicrystal boundary at low temperatures and the second one is spin-flip by antiferromagnetic magnons at high temperatures.
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| 23. |
- Hou, JH, et al.
(författare)
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Polygenic resilience scores capture protective genetic effects for Alzheimer's disease
- 2022
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 296-
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast “resilient” unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected individuals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk.
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| 24. |
- Ovsyannikov, Gennady, 1948, et al.
(författare)
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Triplet superconductivity in oxide ferromagnetic interlayer of mesa-structure
- 2014
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 592:1, s. Art. no. 012136-
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Konferensbidrag (refereegranskat)abstract
- We present experimental data on Nb-Au/La0.7Sr0.3MnO3/SrRuO3/YBa2Cu3O7-δ mesa- structure with in plane linear size 10÷50 μm. The mesa-structures were patterned from the epitaxial heterostructures fabricated by pulsed laser ablation and magnetron sputtering. Superconducting critical current was observed for mesa-structures with the interlayer thicknesses up to 50 nm. In the mesa-structures with just one, either La0.7Sr0.3MnO3 or SrRuO3 interlayer with a thickness larger than 10 nm no superconducting current was observed. The registered superconducting current for the mesa-structures with a thinner interlayer is attributed to pinholes. Obtained results are discussed in terms of superconducting long-range triplet generation at interfaces of superconductor and a composite ferromagnet consisting of ferromagnetic materials with non-collinear magnetization.
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| 25. |
- Petrzhik, A. M., et al.
(författare)
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Electron transport in hybrid superconductor heterostructures with manganite interlayers
- 2011
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Ingår i: Journal of Experimental and Theoretical Physics. - : Pleiades Publishing Ltd. - 1090-6509 .- 1063-7761. ; 112:6, s. 1042-1050
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Tidskriftsartikel (refereegranskat)abstract
- Hybrid herostructures comprising an YBa(2)Cu(3)O (x) (YBCO) high-temperature superconductor (HTS) layer and Nb/Au low-temperature superconductor (LTS) bilayer (with critical HTS and LTS temperatures T (c) and T'(c), respectively), separated by a thin (d (M) = 5-20 nm) interlayer of LaMnO(3), La(0.7)Ca(0.3)MnO(3), or La(0.7)Sr(0.3)MnO(3) manganite have been studied. The electric resistance and magnetic properties of individual (evaporated directly onto the substrate) manganite films and related hybrid herostructures have been measured. Based on quasi-classical equations, analytical expressions for the conductivity of herostructures at T a parts per thousand currency sign T'(c) are obtained in the case of a low-transparency superconductor/manganite interface. It is established that the conductivity of heterostructures is determined by the proximity effect (related to the penetration of a condensate wavefunction from the Nb/Au bilayer to manganite) and depends strongly on interface transparency. At low temperatures (T a parts per thousand(a) T (c)'), the conductivity peaks are found at voltages determined by the exchange field of the manganite interlayer. At T (c)'
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| 26. |
- Petrzhik, A. M., et al.
(författare)
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Spin transport in epitaxial magnetic manganite/ruthenate heterostructures with an LaMnO3 layer
- 2014
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Ingår i: Journal of Experimental and Theoretical Physics. - : Pleiades Publishing Ltd. - 1090-6509 .- 1063-7761. ; 119:4, s. 745-752
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Tidskriftsartikel (refereegranskat)abstract
- Epitaxial La0.7Sr0.3MnO3/LaMnO3/SrRuO3 (LSMO/LMO/SRO) heterostructures with an LMO layer 0-35 nm thick are grown by laser ablation on an NdGaO3 substrate at a high temperature. X-ray diffraction and transmission electron microscopy demonstrate sharp interfaces and epitaxial growth of the LSMO and SRO layers in the heterostructures at an LMO layer thickness of 0-35 nm. SQUID measurements of the magnetic moment of the heterostructures with an LMO layer and the data obtained with reflectometry of polarized neutrons show that the manganite LMO layer is a ferromagnet at a temperature below 150 K and strongly affects the magnetic moment of the heterostructures at low temperatures. The magnetoresistance of the mesostructure created from the heterostructure using lithography and ion etching decreases with increasing LMO layer thickness and weakly depends on the direction of an applied magnetic field. If the LMP layer is absent, a negative magnetoresistance is detected; it is likely to be caused by a negative magnetization of the SRO layer.
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| 27. |
- Sheyerman, A. E., et al.
(författare)
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Current-phase relation of superconductor-ferromagnet-superconductor junctions with a composite interlayer
- 2015
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Ingår i: Solid State Phenomena. - 1662-9779 .- 1012-0394. ; 233-234, s. 737-740
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Konferensbidrag (refereegranskat)abstract
- We report on microwave measurements of hybrid superconductor-ferromagnetsuperconductor (SFF’S’) junctions with a composite oxide ferromagnetic bilayer with non-collinear magnetizations. Current-phase relation (CPR) of the junction superconducting current has been evaluated as a function of magnetic field. A significant part of the 2 nd harmonic in CPR, about 50%, was measured.
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| 28. |
- Sheyerman, A. E., et al.
(författare)
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Spin-triplet electron transport in hybrid superconductor heterostructures with a composite ferromagnetic interlayer
- 2015
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Ingår i: Journal of Experimental and Theoretical Physics. - 1090-6509 .- 1063-7761. ; 120:6, s. 1024-1033
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Tidskriftsartikel (refereegranskat)abstract
- Hybrid YBa2Cu3O7 - x /SrRuO3/La0.7Sr0.3MnO3/Au-Nb superconductor mesastructures with a composite manganite-ruthenate ferromagnetic interlayer are studied using electrophysical, magnetic, and microwave methods. The supercurrent in the mesastructure is observed when the interlayer thickness is much larger than the coherence length of ferromagnetic materials. The peak on the dependence of the critical current density on the interlayer material thickness corresponds to the coherence length, which is in qualitative agreement with theoretical predictions for a system with spit-triplet superconducting correlations. The magnetic-field dependence of the critical current is determined by penetration of magnetic flux quanta and by the magnetic domain structure, as well as by the field dependence of disorientation of the magnetization vectors of the layers in the composite magnetic interlayer. It is found that the supercurrent exists in magnetic fields two orders of magnitude stronger than the field corresponding to entry of a magnetic flux quantum into the mesastructure. The current-phase relation (CPR) of the supercurrent of mesastructures is investigated upon a change in the magnetic field from zero to 30 Oe; the ratio of the second CPR harmonic to the first, determined from the dependence of the Shapiro steps on the microwave radiation amplitude, does not exceed 50%.
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| 29. |
- van der Meer, Dennis, et al.
(författare)
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The link between liver fat and cardiometabolic diseases is highlighted by genome-wide association study of MRI-derived measures of body composition
- 2022
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Ingår i: Communications Biology. - : NATURE PORTFOLIO. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- A GWAS study of European individuals uncovers genetic associations between whole-body MRI derived measures and cardiometabolic diseases and highlights the key role of liver fat in cardiometabolic health. Obesity and associated morbidities, metabolic associated fatty liver disease (MAFLD) included, constitute some of the largest public health threats worldwide. Body composition and related risk factors are known to be heritable and identification of their genetic determinants may aid in the development of better prevention and treatment strategies. Recently, large-scale whole-body MRI data has become available, providing more specific measures of body composition than anthropometrics such as body mass index. Here, we aimed to elucidate the genetic architecture of body composition, by conducting genome-wide association studies (GWAS) of these MRI-derived measures. We ran both univariate and multivariate GWAS on fourteen MRI-derived measurements of adipose and muscle tissue distribution, derived from scans from 33,588 White European UK Biobank participants (mean age of 64.5 years, 51.4% female). Through multivariate analysis, we discovered 100 loci with distributed effects across the body composition measures and 241 significant genes primarily involved in immune system functioning. Liver fat stood out, with a highly discoverable and oligogenic architecture and the strongest genetic associations. Comparison with 21 common cardiometabolic traits revealed both shared and specific genetic influences, with higher mean heritability for the MRI measures (h(2 )= .25 vs. .13, p = 1.8x10(-7)). We found substantial genetic correlations between the body composition measures and a range of cardiometabolic diseases, with the strongest correlation between liver fat and type 2 diabetes (r(g )= .49, p = 2.7x10(-22)). These findings show that MRI-derived body composition measures complement conventional body anthropometrics and other biomarkers of cardiometabolic health, highlighting the central role of liver fat, and improving our knowledge of the genetic architecture of body composition and related diseases.
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| 30. |
- van der Meer, Dennis, et al.
(författare)
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The role of liver fat in cardiometabolic diseases is highlighted by genome-wide association study of MRI-derived measures of body composition
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background & AimsObesity and associated morbidities, metabolic associated liver disease (MAFLD) included, constitute some of the largest public health threats worldwide. Body composition and related risk factors are known to be heritable and identification of their genetic determinants may aid in the development of better prevention and treatment strategies. Recently, large-scale whole-body MRI data has become available, providing more specific measures of body composition than anthropometrics such as body mass index. Here, we aimed to elucidate the genetic architecture of body composition, by conducting the first genome-wide association study (GWAS) of these MRI-derived measures.MethodsWe ran both univariate and multivariate GWAS on fourteen MRI-derived measurements of adipose and muscle tissue distribution, derived from scans from 34,036 White European UK Biobank participants (mean age of 64.5 years, 51.5% female).ResultsThrough multivariate analysis, we discovered 108 loci with distributed effects across the body composition measures and 256 significant genes primarily involved in immune system functioning. Liver fat stood out, with a highly discoverable and oligogenic architecture and the strongest genetic associations. Comparison with 21 common cardiometabolic traits revealed both shared and specific genetic influences, with higher mean heritability for the MRI measures (h2=.25 vs. .16, p=1.4×10−6). We found substantial genetic correlations between the body composition measures and a range of cardiometabolic diseases, with the strongest correlation between liver fat and type 2 diabetes (rg=.48, p=1.6×10−22).ConclusionsThese findings show that MRI-derived body composition measures complement conventional body anthropometrics and other biomarkers of cardiometabolic health, highlighting the central role of liver fat, and improving our knowledge of the genetic architecture of body composition and related diseases.
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| 31. |
- Zaǐtsev, A. V., et al.
(författare)
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Superconducting current in hybrid structures with an antiferromagnetic interlayer
- 2010
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Ingår i: Journal of Experimental and Theoretical Physics. - 1090-6509 .- 1063-7761. ; 110:2, s. 336-344
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Tidskriftsartikel (refereegranskat)abstract
- It is shown experimentally that the superconducting current density in Nb/Au/Ca1 - x Sr (x) CuO2/YBa2Cu3O7 - delta hybrid superconducting heterostructures with a Ca1 - x Sr (x) CuO2 anti-ferromagnetic (AF) cuprate interlayer is anomalously high for interlayer thicknesses d (M) = 10-50 nm and the characteristic damping length for superconducting correlations is on the order of 10 nm. The experimental results are explained on the basis of theoretical analysis of a junction of two superconductors (S' and S) connected by a magnetic multilayer with the AF ordering of magnetization in the layers. It is shown that with such a magnetization ordering, anomalous proximity effect determined by the singlet component of the condensate wavefunction may take place. As a result, the critical currents in S'/I/AF/S and S'/I/N/S structures (I denotes an insulator, and N, the normal metal) may coincide in order of magnitude even when the thickness of the AF interlayer considerably exceeds the decay length of the condensate wavefunction in ferromagnetic layers.
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| 32. |
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| 33. |
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| 34. |
- Kislinskiǐ, Yu V., et al.
(författare)
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Magnetically Dependent Superconducting Transport in Oxide Heterostructures with an Antiferromagnetic Layer
- 2008
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Ingår i: Journal of Experimental and Theoretical Physics. - 1090-6509 .- 1063-7761. ; 106:4, s. 800-805
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Tidskriftsartikel (refereegranskat)abstract
- The superconducting current in hybrid superconducting structuresNb/Au/Ca1−xSrxCuO2/YBa2Cu3O7 –δwith an antiferromagnetic layer is experimentally shown to have aJosephson nature, and the deviation from the sinusoidal dependence of the superconducting current on thephase difference between superconducting electrodes is about 20% of the second harmonic. These heterostructuresare found to have sensitivity to an applied magnetic field that is much higher than that of conventionalJosephson junctions. The experimental shape of the magnetic-field dependence of the critical current in the heterostructuresdiffers from the usual Fraunhofer shape by oscillation with a significantly smaller period along amagnetic field.PACS numbers: 74.45.+c, 74.50.+r, 75.70.Cn
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| 35. |
- Losev, A., et al.
(författare)
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From Zwiebach invariants to Getzler relation
- 2007
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Ingår i: Communications in Mathematical Physics. - : Springer Science and Business Media LLC. - 0010-3616 .- 1432-0916. ; 271:3, s. 649-679
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Tidskriftsartikel (refereegranskat)abstract
- We introduce the notion of Zwiebach invariants that generalize Gromov-Witten invariants and homotopical algebra structures. We outline the induction procedure that induces the structure of Zwiebach invariants on the sub-bicomplex, that gives the structure of Gromov-Witten invariants on sub-bicomplex with zero differentials. We propose to treat Hodge dGBV with 1/12 axiom as the simplest set of Zwiebach invariants, and explicitly prove that it induces WDVV and Getzler equations in genera 0 and 1 respectively.
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| 36. |
- Ovsyannikov, Gennady, 1948, et al.
(författare)
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Triplet superconducting correlations in oxide heterostructures with a composite ferromagnetic interlayer
- 2013
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Ingår i: JETP Letters. - : Pleiades Publishing Ltd. - 1090-6487 .- 0021-3640. ; 97:3, s. 145-148
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Tidskriftsartikel (refereegranskat)abstract
- The superconducting current induced by the penetration of the long-range triplet component of superconducting correlations into a composite ferromagnetic interlayer has been detected in mesa-heterostructures based on oxide cuprate superconductors YBa2Cu3O7 - delta and Au/Nb bilayer films with the composite oxide interlayer that is made of ferromagnetic films of manganite La0.7Sr0.3MnO3 and ruthenate SrRuO3 and has a thickness much larger than the length of correlations determined by the exchange field. The deviation of the superconducting current in the mesa-heterostructure with the fraction of the second harmonic of 13% from a sinusoidal current-phase relation has been detected; this deviation can also be due to the generation of the triplet component of superconducting correlations in the ferromagnet.
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| 37. |
- Petrzhik, A. M., et al.
(författare)
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Electron Transport in Manganite Bicrystal Junctions
- 2013
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Ingår i: Physics of the Solid State. - : Pleiades Publishing Ltd. - 1063-7834 .- 1090-6460. ; 55:4, s. 759-764
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Tidskriftsartikel (refereegranskat)abstract
- The transport and magnetic properties of junctions created in La0.67Sr0.33MnO3 thin films epitaxially grown on substrates with a bicrystal boundary have been investigated. In tilted neodymium gallate bicrystal substrates, the NdGaO3(110) planes are inclined at angles of 12 degrees and 38 degrees. The temperature dependences of the electrical resistance, magnetoresistance, and differential conductance of the junctions at different voltages have been measured and analyzed. It has been found that the magnetoresistance and electrical resistance of the junction significantly increase with an increase in the misorientation angle, even though the misorientation of the easy magnetization axes remains nearly unchanged. The ratio of the spin-dependent and spin-independent contributions to the conductance of the bicrystal junction increases by almost an order of magnitude with an increase in the misorientation angle from 12 degrees to 38 degrees. The magnetoresistance of the junction increases with decreasing temperature, which is most likely associated with an increase of the magnetic polarization of the electrons. It has been shown that, at low (liquid-helium) temperatures, the conductance depends on the voltage V according to the law V-1/2, which indicates the dominant contribution from the electron-electron interaction to the electrical resistance of the junction. An increase in the temperature leads to a decrease in this contribution and an increase in the contribution proportional to V-3/2, which is characteristic of the mechanism involving inelastic spin scattering by surface antiferromagnetic magnons.
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| 38. |
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| 39. |
- Petrzhik, A. M., et al.
(författare)
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Spin-dependent electron transport in manganite bicrystal junctions
- 2012
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Ingår i: Journal of Experimental and Theoretical Physics. - 1090-6509 .- 1063-7761. ; 115:5, s. 876-884
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic bicrystal films and junctions of magnetic La0.67Sr0.33MnO3 (LSMO) and La0.67Ca0.33MnO3 (LCMO) films epitaxially grown on NdGaO3 substrates with the (110) planes of their two parts misoriented (tilted) at angles of 12A degrees, 22A degrees, 28A degrees, and 38A degrees are investigated. For comparison, bicrystal boundaries with a 90A degrees misorientation of the axes of the NdGaO3 (110) planes were fabricated. The directions of the axes and the magnetic anisotropy constants of the films on both sides of the boundary are determined by two independent techniques of magnetic resonance spectroscopy. The magnetic misorientation of the axes in the substrate plane has been found to be much smaller than the crystallographic misorientation for tilted bicrystal boundaries, while the crystallographic and magnetic misorientation angles coincide for boundaries with rotation of the axes. An increase in the magnetoresistance and characteristic resistance of bicrystal junctions with increasing misorientation angle was observed experimentally. The magnetoresistance of bicrystal junctions has been calculated by taking into account the uniaxial anisotropy, which has allowed the contributions from the tunneling and anisotropic magnetoresistances to be separated. The largest tunneling magnetoresistance was observed on LCMO bicrystal junctions, in which the characteristic resistance of the boundary is higher than that in LSMO boundaries.
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| 40. |
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| 41. |
- Werner, MCF, et al.
(författare)
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Immune marker levels in severe mental disorders: associations with polygenic risk scores of related mental phenotypes and psoriasis
- 2022
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 38-
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Tidskriftsartikel (refereegranskat)abstract
- Several lines of evidence implicate immune abnormalities in the pathophysiology of severe mental disorders (SMD) and comorbid mental disorders. Here, we use the data from genome-wide association studies (GWAS) of autoimmune diseases and mental phenotypes associated with SMD to disentangle genetic susceptibilities of immune abnormalities in SMD. We included 1004 patients with SMD and 947 healthy controls (HC) and measured plasma levels of IL-1Ra, sIL-2R, gp130, sTNFR-1, IL-18, APRIL, and ICAM-1. Polygenic risk scores (PRS) of six autoimmune disorders, CRP, and 10 SMD-related mental phenotypes were calculated from GWAS. General linear models were applied to assess the association of PRS with immune marker abnormalities. We found negative associations between PRS of educational attainment and IL-1Ra (P = 0.01) and IL-18 (P = 0.01). There were nominal positive associations between PRS of psoriasis and sgp130 (P = 0.02) and PRS of anxiety and IL-18 (P = 0.03), and nominal negative associations between PRS of anxiety and sIL-2R (P = 0.02) and PRS of educational attainment and sIL-2R (P = 0.03). Associations explained minor amounts of the immune marker plasma-level difference between SMD and HC. Different PRS and immune marker associations in the SMD group compared to HC were shown for PRS of extraversion and IL-1Ra ([interaction effect (IE), P = 0.002), and nominally for PRS of openness and IL-1Ra (IE, P = 0.02) and sTNFR-1 (IE, P = 0.04). Our findings indicate polygenic susceptibilities to immune abnormalities in SMD involving genetic overlap with SMD-related mental phenotypes and psoriasis. Associations might suggest immune genetic factors of SMD subgroups characterized by autoimmune or specific mental features.
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| 42. |
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