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

Key Technologies for the Wide Field Infrared Survey Telescope Coronagraph Instrument

Submitted in response to the 2018 NAS Exoplanet Science Strategy call. 5 pages, 2 figuresThe Wide Field Infrared Survey Telescope (WFIRST) Coronagraph Instrument (CGI) is a high-contrast imager and integral field spectrograph that will enable the study of exoplanets and circumstellar disks at visible wavelengths. Ground-based high-contrast instrumentation has fundamentally limited performance at small working angles, even under optimistic assumptions for 30m-class telescopes. There is a strong scientific driver for better performance, particularly at visible wavelengths. Future flagship mission concepts aim to image Earth analogues with visible light flux ratios of more than 10^10. CGI is a critical intermediate step toward that goal, with a predicted 10^8-9 flux ratio capability in the visible. CGI achieves this through improvements over current ground and space systems in several areas: (i) Hardware: space-qualified (TRL9) deformable mirrors, detectors, and coronagraphs, (ii) Algorithms: wavefront sensing and control; post-processing of integral field spectrograph, polarimetric, and extended object data, and (iii) Validation of telescope and instrument models at high accuracy and precision. This white paper, submitted to the 2018 NAS Exoplanet Science Strategy call, describes the status of key CGI technologies and presents ways in which performance is likely to evolve as the CGI design matures