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- Guintivano, Jerry, et al.
(author)
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Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression
- 2023
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In: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 180:12, s. 884-895
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD.METHOD: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system.RESULTS: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD.CONCLUSIONS: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).
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| 2. |
- Muus, Christoph, et al.
(author)
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Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
- 2021
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 546-559
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Journal article (peer-reviewed)abstract
- Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention. An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.
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| 3. |
- Vuorinen, Katariina E.M., et al.
(author)
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Growth rings show limited evidence for ungulates' potential to suppress shrubs across the Arctic
- 2022
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In: Environmental Research Letters. - : IOP Publishing. - 1748-9318 .- 1748-9326. ; 17:3
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Journal article (peer-reviewed)abstract
- Global warming has pronounced effects on tundra vegetation, and rising mean temperatures increase plant growth potential across the Arctic biome. Herbivores may counteract the warming impacts by reducing plant growth, but the strength of this effect may depend on prevailing regional climatic conditions. To study how ungulates interact with temperature to influence growth of tundra shrubs across the Arctic tundra biome, we assembled dendroecological data from 20 sites, comprising 1153 individual shrubs and 223 63 annual growth rings. Evidence for ungulates suppressing shrub radial growth was only observed at intermediate summer temperatures (6.5 °C-9 °C), and even at these temperatures the effect was not strong. Multiple factors, including forage preferences and landscape use by the ungulates, and favourable climatic conditions enabling effective compensatory growth of shrubs, may weaken the effects of ungulates on shrubs, possibly explaining the weakness of observed ungulate effects. Earlier local studies have shown that ungulates may counteract the impacts of warming on tundra shrub growth, but we demonstrate that ungulates' potential to suppress shrub radial growth is not always evident, and may be limited to certain climatic conditions.
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