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Sökning: WFRF:(Hendricks Alexander) > Karolinska Institutet

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1.
  • Schafmayer, Clemens, et al. (författare)
  • Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms
  • 2019
  • Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 68:5, s. 854-865
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. Design Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. Results We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p< 0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3x10-10 and 0.002 (OR allelic = 1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). Conclusion I n silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.
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2.
  • Honk, Ludwig, et al. (författare)
  • Longitudinal associations between psychedelic use and psychotic symptoms in the United States and the United Kingdom
  • 2024
  • Ingår i: Journal of Affective Disorders. - 0165-0327 .- 1573-2517. ; 351, s. 194-201
  • Tidskriftsartikel (refereegranskat)abstract
    • It has long been speculated that psychedelic use could provoke the onset of psychosis, but there is little evidence to support this conjecture. Using a longitudinal research design with samples representative of the US and UK adult populations with regard to sex, age, and ethnicity (n = 9732), we investigated associations between psychedelic use and change in the number of psychotic symptoms during the two-month study period. In covariate-adjusted regression models, psychedelic use during the study period was not associated with a change in the number of psychotic symptoms unless it interacted with a personal or family history of bipolar disorder, in which case the number of symptoms increased, or with a personal (but not family) history of psychotic disorders, in which case the number of symptoms decreased. Taken together, these findings indicate that psychedelic use may affect psychotic symptoms in individuals with a personal or family history of certain disorders characterized by psychotic symptomatology.
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