Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk

Wind resource mapping using landscape roughness and spatial interpolation methods

Energy saving, reduction of greenhouse gasses and increased use of renewables are key policies to achieve the European 2020 targets. In particular, distributed renewable energy sources, integrated with spatial planning, require novel methods to optimise supply and demand. In contrast with large scale wind turbines, small and medium wind turbines (SMWTs) have a less extensive impact on the use of space and the power system, nevertheless, a significant spatial footprint is still present and the need for good spatial planning is a necessity. To optimise the location of SMWTs, detailed knowledge of the spatial distribution of the average wind speed is essential, hence, in this article, wind measurements and roughness maps were used to create a reliable annual mean wind speed map of Flanders at 10 m above the Earth’s surface. Via roughness transformation, the surface wind speed measurements were converted into meso- and macroscale wind data. The data were further processed by using seven different spatial interpolation methods in order to develop regional wind resource maps. Based on statistical analysis, it was found that the transformation into mesoscale wind, in combination with Simple Kriging, was the most adequate method to create reliable maps for decision-making on optimal production sites for SMWTs in Flanders.

Wind Resource Mapping Using Landscape Roughness and Spatial Interpolation Methods

Energy saving, reduction of greenhouse gasses and increased use of renewables are key policies to achieve the European 2020 targets. In particular, distributed renewable energy sources, integrated with spatial planning, require novel methods to optimise supply and demand. In contrast with large scale wind turbines, small and medium wind turbines (SMWTs) have a less extensive impact on the use of space and the power system, nevertheless, a significant spatial footprint is still present and the need for good spatial planning is a necessity. To optimise the location of SMWTs, detailed knowledge of the spatial distribution of the average wind speed is essential, hence, in this article, wind measurements and roughness maps were used to create a reliable annual mean wind speed map of Flanders at 10 m above the Earth’s surface. Via roughness transformation, the surface wind speed measurements were converted into meso- and macroscale wind data. The data were further processed by using seven different spatial interpolation methods in order to develop regional wind resource maps. Based on statistical analysis, it was found that the transformation into mesoscale wind, in combination with Simple Kriging, was the most adequate method to create reliable maps for decision-making on optimal production sites for SMWTs in Flanders (Belgium).

CODEX: mapping co-created data for speculative geographies

This paper discusses a series of artworks named CODEX produced by the authors as part of a collaborative research project between the Centre for Research in Education, Art and Media (CREAM), University of Westminster, and the Oxford Internet Institute. Taking the form of experimental maps, large-scale installations and prints, we show how big data can be employed to reflect upon social phenomena through the formulation of critical, aesthetic and speculative geographies.