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

Ein mehrsortiger Resolutionskalkuel mit Paramodulation

SEKI-Projekt; with many refs.Copy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Untersuchung der Dynamik des lang- und kurzfristigen Stoffaustrages bei kleinen Einzugsgebieten mit ackerbaulicher Nutzung

Technische Informationsbibliothek Hannover: AC 5843. / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Schubert's steamroller - a case study in many-sorted resolution

SIGLECopy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Measurements in Afghanistan using an active radon exposure meter and assessment of related annual effective dose.

Radon gas concentrations in eight basements, four living rooms and four caves from different locations in Kabul and Panjsher, Afghanistan, were measured by using eight active radon exposure meters recently developed by the Helmholtz Center in Munich, Germany. The two-phase measurements lasted from a week to a year. In the first phase of measurements which lasted one week, the mean activity concentrations ranged from 6 to 120 Bq/m 3 and 25 to 139 Bq/m 3 for the basements and caves, respectively. In the second phase of measurements which lasted one year, the mean activity concentrations ranged from 33 to 2064 Bq/m 3 and the corresponding effective annual doses calculated for the inhabitants were in the range between 0.6 and 33.4 mSv. As some of the values are rather high and exceed the recommended recommendations by IAEA and ICRP, based on the local conditions a number of simple recommendations has been proposed for the possible reduction of effective annual dose caused by radon in the measurement locations

Untersuchung der Beziehung zwischen elektrischer Leitfaehigkeit und Ionenkonzentration bei ausgewaehlten Guetepegeln an Fluessen Niedersachsens Bericht

TIB: AC 7250+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Kurse fuer auffaellige Kraftfahrer Zwischenbericht 1980

TIB: RN 7380 (7) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman