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- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 3. |
- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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| 4. |
- Mawet, Dimitri, et al.
(författare)
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L '-band AGPM vector vortex coronagraph's first light on VLT/NACO Discovery of a late-type companion at two beamwidths from an F0V star
- 2013
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 552, s. L13-
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Tidskriftsartikel (refereegranskat)abstract
- Context. High contrast imaging has thoroughly combed through the limited search space accessible with first-generation ground-based adaptive optics instruments and the Hubble Space Telescope. Only a few objects were discovered, and many non-detections reported and statistically interpreted. The field is now in need of a technological breakthrough. Aims. Our aim is to open a new search space with first-generation systems such as NACO at the Very Large Telescope, by providing ground-breaking inner working angle (IWA) capabilities in the L' band. The L' band is a sweet spot for high contrast coronagraphy since the planet-to-star brightness ratio is favorable, while the Strehl ratio is naturally higher. Methods. An annular groove phase mask (AGPM) vector vortex coronagraph optimized for the L' band made from diamond subwavelength gratings was manufactured and qualified in the lab. The AGPM enables high contrast imaging at very small IWA, potentially being the key to unexplored discovery space. Results. Here we present the installation and successful on-sky tests of an L'-band AGPM coronagraph on NACO. Using angular differential imaging, which is well suited to the rotational symmetry of the AGPM, we demonstrated a Delta L' > 7.5 mag contrast from an IWA similar or equal to 0 ''.09 onwards, during average seeing conditions, and for total integration times of a few hundred seconds.
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| 7. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 8. |
- Milli, J., et al.
(författare)
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Discovery of a low-mass companion inside the debris ring surrounding the F5V star HD 206893
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 597
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Tidskriftsartikel (refereegranskat)abstract
- Aims. Uncovering the ingredients and the architecture of planetary systems is a very active field of research that has fuelled many new theories on giant planet formation, migration, composition, and interaction with the circumstellar environment. We aim at discovering and studying new such systems, to further expand our knowledge of how low-mass companions form and evolve.Methods. We obtained high-contrast H-band images of the circumstellar environment of the F5V star HD 206893, known to host a debris disc never detected in scattered light. These observations are part of the SPHERE High Angular Resolution Debris Disc Survey (SHARDDS) using the InfraRed Dual-band Imager and Spectrograph (IRDIS) installed on VLT/SPHERE.Results. We report the detection of a source with a contrast of 3.6 × 10−5 in the H-band, orbiting at a projected separation of 270 milliarcsecond or 10 au, corresponding to a mass in the range 24 to 73MJup for an age of the system in the range 0.2 to 2 Gyr. The detection was confirmed ten months later with VLT/NaCo, ruling out a background object with no proper motion. A faint extended emission compatible with the disc scattered light signal is also observed.Conclusions. The detection of a low-mass companion inside a massive debris disc makes this system an analog of other young planetary systems such as β Pictoris, HR 8799 or HD 95086 and requires now further characterisation of both components to understand their interactions.
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| 9. |
- Chitica, N, et al.
(författare)
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Fabrication of tunable InP/air-gap Fabry-Perot cavities by selective etching of InGaAs sacrificial layers
- 1999
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Ingår i: Physica scripta. T. - : ROYAL SWEDISH ACAD SCIENCES. - 0281-1847. ; T79, s. 131-134
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Tidskriftsartikel (refereegranskat)abstract
- We report the fabrication of InP/air-gap Fabry-Perot resonant cavities with an improved tunability characteristic achieved through the micromachining of more flexible suspended InP beams. The micromechanical structures are electrostatically actuated. A tuning range of 55 nm is demonstrated for an actuation voltage of 12 V. The low leakage current, of less than 10 µA for a bias of up to 30 V, provides a low actuation power. The tunable air-gap cavities are fabricated by selective wet etching of InGaAs sacrificial layers. An FeCl3 based etchant is used to completely remove the InGaAs material without affecting the thickness of the InP layer. The anisotropy of the etch rate of InGaAs was also investigated and exploited in the micromachining process.
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| 10. |
- Defrere, D., et al.
(författare)
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L'-band AGPM vector vortex coronagraph's first light on LBTI/LMIRCam
- 2014
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Ingår i: Adaptive Optics Systems IV. - : SPIE. - 9780819496164
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Konferensbidrag (refereegranskat)abstract
- We present the first observations obtained with the L'-band AGPM vortex coronagraph recently installed on LBTI/LMIRCam. The AGPM (Annular Groove Phase Mask) is a vector vortex coronagraph made from diamond subwavelength gratings. It is designed to improve the sensitivity and dynamic range of high-resolution imaging at very small inner working angles, down to 0.09 arcseconds in the case of LBTI/LMIRCam in the L' band. During the first hours on sky, we observed the young A5V star HR8799 with the goal to demonstrate the AGPM performance and assess its relevance for the ongoing LBTI planet survey (LEECH). Preliminary analyses of the data reveal the four known planets clearly at high SNR and provide unprecedented sensitivity limits in the inner planetary system (down to the diffraction limit of 0.09 arcseconds).
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