8 research outputs found

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    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

    Radionuclide and stable elements in flora from Australian arid environments

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    Dataset made available per the CC BY 4.0 Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/Radiological impact assessments are an important tool for energy and resources industries and government safety regulators to assist in the protection of wildlife diversity, especially native species. Evaluations of radiological impacts to flora in the arid regions of Australia are currently based on international models that use predominately Northern Hemisphere data, with very limited Australian-specific data. This creates a degree of uncertainty in communicating the potential impact of relevant Australian assessments. The project aims to build an improved understanding of radionuclide concentration ratios and radionuclide pathways in arid Australian conditions and are expected to inform assessments in similar environmental conditions elsewhere. The dataset contains measurement of stable elements and radionuclides in soils and plants that were obtained from three regions in South Australia: Flinders Ranges, Pernatty and Roxby Downs region. Access to Australian specific data for use in radiological impact models provide a better understanding and more credible environmental impact assessment process based on more relevant local information

    Identification of seven new prostate cancer susceptibility loci through a genome-wide association study

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    Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. To identify common PrCa susceptibility alleles, we have previously conducted a genome-wide association study in which 541, 129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and 1,894 controls. We have now evaluated promising associations in a second stage, in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls, and a third stage, involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to previously identified loci, we identified a further seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11, and 22 (P=1.6×10−8 to P=2.7×10−33)
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