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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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- Rockström, Johan, et al.
(författare)
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The unfolding water drama in the Anthropocene : towards a resilience-based perspective on water for global sustainability
- 2014
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Ingår i: Ecohydrology. - : Wiley. - 1936-0584 .- 1936-0592. ; 7:5, s. 1249-1261
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Tidskriftsartikel (refereegranskat)abstract
- The human influence on the global hydrological cycle is now the dominant force behind changes in water resources across the world and in regulating the resilience of the Earth system. The rise in human pressures on global freshwater resources is in par with other anthropogenic changes in the Earth system (from climate to ecosystem change), which has prompted science to suggest that humanity has entered a new geological epoch, the Anthropocene. This paper focuses on the critical role of water for resilience of social-ecological systems across scales, by avoiding major regime shifts away from stable environmental conditions, and in safeguarding life-support systems for human wellbeing. It highlights the dramatic increase of water crowding: near-future challenges for global water security and expansion of food production in competition with carbon sequestration and biofuel production. It addresses the human alterations of rainfall stability, due to both land-use changes and climate change, the ongoing overuse of blue water, reflected in river depletion, expanding river basin closure, groundwater overexploitation and water pollution risks. The rising water turbulence in the Anthropocene changes the water research and policy agenda, from a water-resource efficiency to a water resilience focus. This includes integrated land and water stewardship to sustain wetness-dependent ecological functions at the landscape scale and a stronger emphasis on green water management for ecosystem services. A new paradigm of water governance emerges, encouraging land-use practices that explicitly take account of the multifunctional roles of water, with adequate attention to planetary freshwater boundaries and cross-scale interactions.
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