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

Spanning the Centuries: The historic bridges of Northamptonshire

This book, specially commissioned by Northamptonshire County Council (and written, designed and photographed by MOLA, with a Foreword by Tony Ciaburro of NCC), celebrates the rich diversity of the county’s historic bridges, specifically the 104 Listed by Historic England. There are many more within the county but these may be said to represent the best ones and moreover reveal the hsitory and development of bridges over time. These bridges include one Roman (although long-buried), 38 ‘historic’ bridges, ranging in date from the 13th to the 19th century, and another 20 ‘ornamental’ bridges within the great landscaped estates that Northamptonshire is famous for. The technical ingenuity that came with the Industrial Revolution is represented by the new bridges for canals and railways

Shakespeare's London theatreland: archaeology, history and drama

This guide to the unique theatrical venues of London, from 1567, when the first playhouse was built, to 1642, when Parliament closed them down, sets out the rich dramatic history of this period in relation to the latest exciting archaeological evidence. The book also details the people involved – the builders, actors, playwrights and audiences – what they wore and what they ate, where they drank, where they fought, where they lived and died. There are theatrical quotes and jokes, and illustrations old and new, while a series of walks explores different areas of today’s London, where glimpses of Shakespeare’s London can still be caught

The Rose and Globe - playhouses of Shakespeare's Bankside, Southwark

Excavations at the sites of two famous playhouses of Tudor London, the Rose and the Globe in Southwark, provided physical evidence for the size, layout and development of these playhouses; they are presented here in detail for the first time in 400 years.The hundreds of individual structural elements, objects and plant and animal remains found are described and, together with the freshly researched documentary sources on Shakespearean theatre, fully integrated into the chronological narratives and thematic discussions of every aspect of the playhouses. This archaeological report aims to integrate all strands of evidence and appeal to a wider audience of those interested in the history and development of the theatre