Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.
Almost half of the staff surveyed in our hospital were satisfied or highly satisfied with the organizational climate. Satisfaction was strongly associated with positive evaluation of organizational characteristics.
Although the main causes of Hardy-Weinberg disequilibrium in controls are selection bias or genotyping error, a competing risk of death associated with the mutant gene would also result in Hardy-Weinberg disequilibrium among controls.
Background: Burnout syndrome is an increasingly frequent pathology that is related to people that suffer a deterioration in their daily activities due to highly demandant psychological requirements in their workplaces. Within last decades, burnout syndrome has been studied across medical professionals, concluding that physicians suffer stress levels high enough to make them develop it. Recently, attention has also been paid to medical students, although with small samples. Given that this phenomenon may produce a huge impact in medical students´ development, the aim of this study is to analyze the influential factors that may contribute to its occurrence. Methods: The necessary information was gathered through a web-based questionnaire, divided in two parts. The first part of the survey included questions related to personal aspects of the students. Burnout related questions (second part) were divided in three subscales to evaluate exhaustion, cynicism, and academic efficacy levels. Results: Family support for studying medicine is associated with lower burnout levels in all three scales of the Maslach Burnout Inventory. The number of years spent in the degree show the opposite trend: the more years in the degree, the higher score in all burnout scales. High percentage of Spanish medical students score high in one or more subscales composing burnout syndrome.Conclusions: Burnout syndrome is a problem among medical students in Spain that increases with the number of years studying medicine. It should be also noticed that family support and vocational studies are independent factors related to lower levels of burnout.
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