Germline variation at 8q24 and prostate cancer risk in men of European ancestry

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

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

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. © 2018 The Author(s).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. © 2018 The Author(s).Peer reviewe

Population locality dat Coordinates.Status

This file provides location data for sites where multiple host species were present and movement of Microbotryum spores was quantified between them

Sympatry and interference of divergent Microbotryum pathogen species

The impact of infectious diseases in natural ecosystems is strongly influenced by the degree of pathogen specialization and by the local assemblies of potential host species. This study investigated anther-smut disease, caused by fungi in the genus Microbotryum, among natural populations of plants in the Caryophyllaceae. A broad geographic survey focused on sites of the disease on multiple host species in sympatry. Analysis of molecular identities for the pathogens revealed that sympatric disease was most often due to co-occurrence of distinct, host-specific anther-smut fungi, rather than localized cross-species disease transmission. Flowers from sympatric populations showed that the Microbotryum spores were frequently moved between host species. Experimental inoculations to simulate cross-species exposure to the pathogens in these plant communities showed that the anther-smut pathogen was less able to cause disease on its regular host when following exposure of the plants to incompatible pathogens from another host species. These results indicate that multi-host/multi-pathogen communities are common in this system and they involve a previously hidden mechanism of interference between Microbotryum fungi, which likely affects both pathogen and host distributions

Data from: Sympatry and interference of divergent Microbotryum pathogen species.

The impact of infectious diseases in natural ecosystems is strongly influenced by the degree of pathogen specialization and by the local assemblies of potential host species. This study investigated anther-smut disease, caused by fungi in the genus Microbotryum, among natural populations of plants in the Caryophyllaceae. A broad geographic survey focused on sites of the disease on multiple host species in sympatry. Analysis of molecular identities for the pathogens revealed that sympatric disease was most often due to co-occurrence of distinct, host-specific anther-smut fungi, rather than localized cross-species disease transmission. Flowers from sympatric populations showed that the Microbotryum spores were frequently moved between host species. Experimental inoculations to simulate cross-species exposure to the pathogens in these plant communities showed that the anther-smut pathogen was less able to cause disease on its regular host when following exposure of the plants to incompatible pathogens from another host species. These results indicate that multi-host / multi-pathogen communities are common in this system and they involve a previously hidden mechanism of interference between Microbotryum fungi, which likely affects both pathogen and host distributions

Rebirth Fashion: Secondhand clothing consumption values and perceived risks

In recent years, the circular economy of alternative consumption models for secondhand goods has become a subject of prominence. However, very little research has been carried out to obtain an in-depth understanding of the negative or positive consumer attitudes, motivations, and values behind secondhand clothing consumption. Therefore, the aim of this study is to investigate the perceived risks and barriers to utilizing secondhand clothing and to identify the enabling and disabling factors that influence its consumption. Two empirical semiqualitative studies were carried out among secondhand clothing consumers (n=134) and non-secondhand clothing consumers (n=138) in the UK to investigate their attitudes, values, and perceptions of risk regarding secondhand clothing consumption. The study incorporated a qualitative means-end value model with a quantitative research technique to construct hierarchical value maps. The results show that consumer perceptions of secondhand fashion products and services differ significantly. The five main values identified among secondhand clothing consumers were: economic, self-expressive, hedonic, environmental, and social contribution values. Non-secondhand clothing consumers exhibited concerns about used clothing consumption due to perceived poor product quality and cleanliness, limitations in the degree of possible self-enhancement and expressibility of self-identity, and a perceived social image of the clothes as low-class and having low social acceptance. The study’s findings concerning secondhand clothing consumption values held by the market and consumers’ perceived risk dimensions can assist retailers and marketers to create a more tailored retailing and promotional strategy