Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

Contextualising video game engagement and addiction in mental health: the mediating roles of coping and social support

Introduction: A challenge in defining Internet Gaming Disorder (IGD) is discriminating pathological gameplay from an excessive, yet benign, involvement in video games. Although previous research has explored this theoretical distinction in the context of general computing activities, it merits consideration with regards to online gaming. Additionally, whilst comorbidities of addicted gaming and mental health outcomes have been robustly demonstrated, few studies have examined the role of mediating factors that may contextualise this relationship. As such, the present study aims to validate the distinction between addiction and engagement in online gaming, by considering the mediating roles of coping and social online and offline support in mental health. Method: One hundred and thirty-five participants completed the Computer Engagement/Addiction Questionnaire (CEAS), Depression-Anxiety-Stress Scale (DASS-21), Brief Approach-Avoidance Coping Questionnaire (BACQ) and two versions of the Multidimensional Scale of Perceived Social Support (MSPSS). Results: Correlational analyses showed a clear distinction between gaming addiction and engagement in the context of all of depression, stress and in particular anxiety (DAS) not found in previous studies. Multiple mediation analysis showed a significant mediating effect of coping, (specifically withdrawal/resignation coping) on the relationship between video game addiction and symptoms of DAS. Offline perceived social support was a significant partial mediator in the relationship between gaming addiction and depression, as compared to any kind of online social support. The results support the distinction of the addiction and engagement concepts in gaming. This study may inform future clinical classifications of IGD, with implications on how pathological gaming is treated