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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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| 5. |
- Lis, D. C., et al.
(författare)
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Herschel/HIFI measurements of the ortho/para ratio in water towards Sagittarius B2(M) and W31C
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L26 -
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Tidskriftsartikel (refereegranskat)abstract
- We present Herschel/HIFI observations of the fundamental rotational transitions of ortho- and para-H216O and H218O in absorption towards Sagittarius B2(M) and W31C. The ortho/para ratio in water in the foreground clouds on the line of sight towards these bright continuum sources is generally consistent with the statistical high-temperature ratio of 3, within the observational uncertainties. However, somewhat unexpectedly, we derive a low ortho/para ratio of 2.35 +/- 0.35, corresponding to a spin temperature of similar to 27 K, towards Sagittarius B2(M) at velocities of the expanding molecular ring. Water molecules in this region appear to have formed with, or relaxed to, an ortho/para ratio close to the value corresponding to the local temperature of the gas and dust.
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- Indriolo, N., et al.
(författare)
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Herschel Survey of Galactic OH+, H2O+, and H3O+: Probing the Molecular Hydrogen Fraction and Cosmic-Ray Ionization Rate
- 2015
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 800:1, s. 40-
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Tidskriftsartikel (refereegranskat)abstract
- In diffuse interstellar clouds the chemistry that leads to the formation of the oxygen-bearing ions OH+, H2O+, and H3O+ begins with the ionization of atomic hydrogen by cosmic rays, and continues through subsequent hydrogen abstraction reactions involving H2. Given these reaction pathways, the observed abundances of these molecules are useful in constraining both the total cosmic-ray ionization rate of atomic hydrogen (ζH) and molecular hydrogen fraction (f_H_2). We present observations targeting transitions of OH+, H2O+, and H3O+ made with the Herschel Space Observatory along 20 Galactic sight lines toward bright submillimeter continuum sources. Both OH+ and H2O+ are detected in absorption in multiple velocity components along every sight line, but H3O+ is only detected along 7 sight lines. From the molecular abundances we compute f_H_2 in multiple distinct components along each line of sight, and find a Gaussian distribution with mean and standard deviation 0.042 ± 0.018. This confirms previous findings that OH+ and H2O+ primarily reside in gas with low H2 fractions. We also infer ζH throughout our sample, and find a lognormal distribution with mean log (ζH) = –15.75 (ζH = 1.78 × 10–16 s–1) and standard deviation 0.29 for gas within the Galactic disk, but outside of the Galactic center. This is in good agreement with the mean and distribution of cosmic-ray ionization rates previously inferred from H_3^+ observations. Ionization rates in the Galactic center tend to be 10-100 times larger than found in the Galactic disk, also in accord with prior studies.
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