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

Land degradation, stocking rates and conservation policies in the communal rangelands of Botswana and Zimbabwe

Communal rangeland management policies in Botswana and Zimbabwe are based on incorrect technical assumptions about the stability of semiarid rangeland, the nature of rangeland degradation, and the benefits of destocking. Consequently, inappropriate policies, stressing the need to destock and stabilise the rangelands, are pursued. Acknowledgement of the great instability but intrinsic resilience of rangeland would encourage the Governments to regard the opportunistic stocking strategies of the agro-pastoralists of the Communal Areas more favourably. However, degradation of rangelands is occurring, although at varying rates. This justifies the promotion of a "tracking strategy', in which livestock densities are encouraged to follow, more closely than at present, variations in rainfall. The establishment of grazing territories controlled by specific "communities' may be a prerequisite for the promotion of the tracking strategy, and for communal rangeland management and improvement. However, the establishment of such territories must take into account social equity, institutional problems and transaction costs, as well as spatial and temporal variation in rangeland resources