10 research outputs found
Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease
Das Analkarzinom: Bedeutung der interdisziplinären Zusammenarbeit im Hinblick auf Kontinenzerhalt und Überleben
Einfluß des benutzten Staplers auf die Komplikationen und Reoperationen nach Stapler-Hämorrhoidopexie
Stabilizing Group Treatment for Complex Posttraumatic Stress Disorder Related to Child Abuse Based on Psychoeducation and Cognitive Behavioural Therapy: A Multisite Randomized Controlled Trial
Background: Evidence-based treatments for complex posttraumatic stress disorder (PTSD) related to childhood abuse are scarce. This is the first randomized controlled trial to test the efficacy of psycho-educational and cognitive behavioural stabilizing group treatment in terms of both PTSD and complex PTSD symptom severity. Methods: Seventy-one patients with complex PTSD and severe comorbidity (e.g. 74% axis II comorbidity) were randomly assigned to either a 20-week group treatment in addition to treatment as usual or to treatment as usual only. Primary outcome measures were the Davidson Trauma Scale (DTS) for PTSD and the Structured Interview for Disorders of Extreme Stress (SIDES) for complex PTSD symptoms. Statistical analysis was conducted in the intention-to-treat (ITT) and in the completer sample. Subjects were considered responders when scoring at 20 weeks at least 1 standard deviation below pretest findings. Results: The 16% attrition was relatively low. After 20 weeks, the experimental condition (large effect sizes) and control condition (medium effect sizes) both showed significant decreases on the DTS and SIDES, but differences between the conditions were not significant. The secondary responder analysis (ITT) revealed significantly more responders on the DTS (45 vs. 21%), but not on the SIDES (61 vs. 42%). Conclusions: Adding psycho-educational and cognitive behavioural stabilizing group treatment for complex PTSD related to child abuse to treatment as usual showed an equivocal outcome. Patients in both conditions improved substantially during stabilizing treatment, and while significant superiority on change scores was absent, responder analysis suggested clinical meaningfulness of adding group treatment. Copyright © 2012 S. Karger AG
Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease
Objective Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date. Design We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry. Results We demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix. Conclusion HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction
Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease
Objective Haemorrhoidal disease (HEM) affects a large and silently
suffering fraction of the population but its aetiology, including
suspected genetic predisposition, is poorly understood. We report the
first genome-wide association study (GWAS) meta-analysis to identify
genetic risk factors for HEM to date. Design We conducted a GWAS
meta-analysis of 218 920 patients with HEM and 725 213 controls of
European ancestry. Using GWAS summary statistics, we performed multiple
genetic correlation analyses between HEM and other traits as well as
calculated HEM polygenic risk scores (PRS) and evaluated their
translational potential in independent datasets. Using functional
annotation of GWAS results, we identified HEM candidate genes, which
differential expression and coexpression in HEM tissues were evaluated
employing RNA-seq analyses. The localisation of expressed proteins at
selected loci was investigated by immunohistochemistry. Results We
demonstrate modest heritability and genetic correlation of HEM with
several other diseases from the GI, neuroaffective and cardiovascular
domains. HEM PRS validated in 180 435 individuals from independent
datasets allowed the identification of those at risk and correlated with
younger age of onset and recurrent surgery. We identified 102
independent HEM risk loci harbouring genes whose expression is enriched
in blood vessels and GI tissues, and in pathways associated with smooth
muscles, epithelial and endothelial development and morphogenesis.
Network transcriptomic analyses highlighted HEM gene coexpression
modules that are relevant to the development and integrity of the
musculoskeletal and epidermal systems, and the organisation of the
extracellular matrix. Conclusion HEM has a genetic component that
predisposes to smooth muscle, epithelial and connective tissue
dysfunction