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

Remembering obedience and dissent: democratic citizenship and memorials to state violence in Australia and Argentina

Memorials to state violence can be read as cultural ledgers of what constitutes legitimate citizenship practice and acceptable citizen-state relations. I explore the significance of Argentinian and Australian memorials for understanding how past political action shapes a horizon of political possibility. Firstly, I examine how ANZAC memorials celebrate empire, obedience and the status quo. Here, there is a contrived unity of state and citizen that disappears questions of power, difference and dissent on which struggles for the expansion of citizenship in Australia and elsewhere have rested. ANZAC exists in a field of other memorials and cultural texts in Australia that negate politics and possibility for emancipation. Then, I discuss several Argentinian memorials that reflect the diversity of Argentina's politics of memory. Some memory spaces represent an open-ended view of the political process, while others are inseparable from a simplified dictatorship-democracy dichotomy. While questions of popular complicity in the state violence of the 1970s have yet to be memorialised, Argentine memorials nonetheless recognize the legitimacy of dissent as a basis of democratic citizenship. Finally, I draw out the significance of the comparison by discussing memorials in relation to theories of citizen agency. This problematizes the northwest-centric view of democracy as end, and reveals the importance of remembering challenges to power as a basis for ongoing democratization. Argentina's memory debates have created new dialogical networks spanning government and advocacy groups that have secured, momentarily at least, the right to claim rights and possibilities for agonistic memory. Australia's memorials, on the other hand, celebrate neither emancipatory struggles nor their proxies in rights, and are more in line with the contrived consensus characteristic of a securitarian state. Based on a comparison of memorials in relation to theories of democratic citizenship, Australia's political subjectivity is amenable to dedemocratization while Argentina's reflects the possibility of open-ended democratization

Multiple loci on 8q24 associated with prostate cancer susceptibility

Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility