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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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- Bakhai, A, et al.
(författare)
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Treatment, outcomes, costs, and quality of life of women and men with acute coronary syndromes who have undergone percutaneous coronary intervention: results from the antiplatelet therapy observational registry
- 2013
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Ingår i: Postgraduate medicine. - : Informa UK Limited. - 0032-5481 .- 1941-9260. ; 125:2, s. 100-107
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Treatment, outcomes, costs, and quality of life after percutaneous coronary intervention (PCI) were compared between women and men with acute coronary syndromes (ACS) using data from the Antiplatelet Therapy Observational Registry (APTOR). METHODS: Fourteen European countries participated in this noninterventional, prospective, observational cohort registry, which enrolled patients with ACS who underwent PCI from 2007 to 2009. The 12-month outcomes included bleeding, cardiovascular events, and mortality. Quality of life was measured using the EQ-5D (EuroQol Group) health index and the visual analog scale. RESULTS: The APTOR registry included 4546 patients, of whom 1047 (23%) were women and 3499 (77%) were men. The women were older (mean age, 67 vs 61 years) and had higher rates of diabetes mellitus and hypertension. A greater proportion of the men were smokers (40% vs 30%). Approximately 70% of the patients underwent PCI on the day of the qualifying ACS event. Women and men received similar medications at the time of PCI, hospital discharge, and 12-month follow-up visit. Bleeding, cardiovascular events, and mortality occurred at higher rates in women than in men, but the differences were not statistically significant. At 12 months post-PCI, women reported lower quality-of-life scores on the EQ-5D health index and the visual analog scale than did men. The mean total cost of care was pound6252 (euro7189) for women and pound5841 (euro6717) for men; the differences may be driven by resource use after discharge from the hospital. CONCLUSION: Women with ACS tended to be older and had more comorbidities than men, but both sexes experienced similar outcomes after 1 year. This study indicated no differences in treatment between sexes.
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