Hydro-morphodynamics 2D modelling using a discontinuous Galerkin discretisation

The development of morphodynamic models to simulate sediment transport accurately is a challenging process that is becoming ever more important because of our increasing exploitation of the coastal zone, as well as sea-level rise and the potential increase in strength and frequency of storms due to a changing climate. Morphodynamic models are highly complex given the non-linear and coupled nature of the sediment transport problem. Here we implement a new depth-averaged coupled hydrodynamic and sediment transport model within the coastal ocean model Thetis, built using the code generating framework Firedrake which facilitates code flexibility and optimisation benefits. To the best of our knowledge, this represents the first full morphodynamic model including both bedload and suspended sediment transport which uses a discontinuous Galerkin based finite element discretisation. We implement new functionalities within Thetis extending its existing capacity to model scalar transport to modelling suspended sediment transport, incorporating within Thetis options to model bedload transport and bedlevel changes. We apply our model to problems with non-cohesive sediment and account for effects of gravity and helical flow by adding slope gradient terms and parametrising secondary currents. For validation purposes and in demonstrating model capability, we present results from test cases of a migrating trench and a meandering channel comparing against experimental data and the widely-used model Telemac-Mascaret

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe