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

Reliability analysis of photovoltaic systems

Reliability is an important parameter for the user of photovoltaic (PV) power systems. A methodology for the analytical treatment of the reliability of PV systems is proposed in this paper. The method depends upon the logic of the fault-tree technique. The reliabilities of the different components of a PV system are used to predict the reliability of the overall system. Today's most commonly known systems are considered and a reliability formula is developed for each system. The methodology presented is appropriate for a wide range of applications and system types.

Social acceptance of renewable energy technologies for buildings in the Helsinki Metropolitan Area of Finland

The application of renewable energy technologies (RETs) in the residential building sector requires acceptance of technical solutions by key stakeholders, such as building owners, real-estate developers, and energy providers. The objective of this study is to identify the current status of public perceptions of RETs that are available in the Finnish market and associated influencing factors, such as perceived reliability, investment cost, payback time, and national incentives. A web-based questionnaire was disseminated to the general public in the Helsinki Metropolitan Area (n = 246). Social perceptions of building-integrated RETs were evaluated through integration of survey data and Stochastic Multicriteria Acceptability Analysis (SMAA), which was applied to analyse the robustness of the survey results. The SMAA demonstrated that Finnish residents exhibit broad acceptance of multiple options, rather than preference for a single RET. Solar technologies and ground source heat pumps were the most preferred options and evaluated as very reliable, whereas wind-based technologies and combined heat and power were ranked as the least popular. In general, respondents indicated a strong willingness to financially invest in RETs as a means to reduce their carbon footprint and preferred tax deductions as an incentive to invest in RETs.</p

Social acceptance of renewable energy technologies for buildings in the Helsinki Metropolitan Area of Finland

The application of renewable energy technologies (RETs) in the residential building sector requires acceptance of technical solutions by key stakeholders, such as building owners, real-estate developers, and energy providers. The objective of this study is to identify the current status of public perceptions of RETs that are available in the Finnish market and associated influencing factors, such as perceived reliability, investment cost, payback time, and national incentives. A web-based questionnaire was disseminated to the general public in the Helsinki Metropolitan Area (n = 246). Social perceptions of building-integrated RETs were evaluated through integration of survey data and Stochastic Multicriteria Acceptability Analysis (SMAA), which was applied to analyse the robustness of the survey results. The SMAA demonstrated that Finnish residents exhibit broad acceptance of multiple options, rather than preference for a single RET. Solar technologies and ground source heat pumps were the most preferred options and evaluated as very reliable, whereas wind-based technologies and combined heat and power were ranked as the least popular. In general, respondents indicated a strong willingness to financially invest in RETs as a means to reduce their carbon footprint and preferred tax deductions as an incentive to invest in RETs

Increased Prevalence of Malignancies in Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS): Data from a National Referral Center and the Dutch National Pathology Registry (PALGA)

Malignant transformation of fibrous dysplasia lesions has been reported in patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS). Recently, we have observed an increased risk for breast cancer. In this study, the prevalence of skeletal and extraskeletal malignancies in patients with FD/MAS in the Netherlands was assessed by analyzing data from our cohort of FD/MAS patients, the Dutch Pathology Registry (PALGA), and the Netherlands Cancer Registry (NCR). We extracted data on sex, age at diagnosis of FD/MAS, type of FD/MAS, type of malignancy, and age at diagnosis of malignancy and histology of bone and malignant tissue when available, including GNAS-mutation analysis from patients' medical records. Standardized Morbidity Ratios (SMRs) with 95% confidence intervals were calculated. Twelve malignancies were identified in the LUMC FD/MAS cohort and 100 in the PALGA cohort. In this cohort, SMR was increased for osteosarcoma (19.7, 95% CI 3.5-48.9), cervical cancer (4.93, 95%CI 1.7-8.2), thyroid cancer (3.71, 95% CI 1.1-7.8), prostate cancer (3.08, 95% CI 1.8-4.6), and melanoma (2.01, 95%CI 1.2-3.1). SMRs for pancreatic cancer or hepatocellular carcinoma could not be calculated due to low numbers. The small number of malignancies identified in our FD/MAS cohort precluded the calculation of SMRs for our cohort specifically. Our findings show that patients with FD/MAS appear to have an increased risk for osteosarcoma, cervical, thyroid, and prostate cancer and melanoma. However, these data should be interpreted with caution, as true incidence rates of the identified malignancies may be influenced by the inclusion of only patients with histologically confirmed FD/MAS. The etiology of this increased risk for malignancies still needs to be elucidated.Clinical epidemiolog