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

Height, selected genetic markers and prostate cancer risk:Results from the PRACTICAL consortium

Background: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. Methods: We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions. Results: The results suggest that height is associated with high-grade prostate cancer risk. Men with height 4180cm are at a 22% increased risk as compared to men with height o173cm (OR 1.22, 95% CI 1.01–1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group. Conclusions: There was no evidence of gene-environment interaction between height and the selected candidate SNPs. Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.</p

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa

Critical board game modification : Changing board games to change the world

Working board game designer and scholar Greg Loring-Albright, PhD will present a talk about changing board games to incite social change. Hobby board gaming, as theorized by scholars like Paul Booth (2018) and Stewart Woods (2012) has been and continues to be a growing subculture, fandom, and market. Games like Catan (Teuber, 1995), Ticket to Ride (Moon, 2004), and Wingspan (Hargrave, 2019) are the result of design interventions by inspired designers. However, board games lag behind other entertainment media like film, TV, and video games when it comes to depicting social change and representing marginalized groups. Greg works to change this, both by designing and publishing new games (e.g. Bloc by Bloc: Uprising, 2022, co-designed with T.L. Simons; Keep the Faith, 2024) and by creating frameworks for modifying existing games (e.g. First Nations of Catan, 2015). This talk will address a general audience, briefly describing the world of hobby board gaming, showcasing some of its problematic dynamics (drawing upon Flanagan and Jakobsson, 2023, among others), and offering paths for other designers and interested amateurs to create their own interventions in the space by modifying the board games that they already play. In addition, Greg will propose a theory of how board games incite social change, developed from close observation of hundreds of board gaming sessions, both in a research context and while playtesting games for publication. Many approaches to games optimistically presuppose a level of impact on the player that may not be justified. Yet board games can change their players, primarily via the discursive opportunities that they afford around the table.Non UBCUnreviewedFacult

Platforming the past: Nostalgia, video games, and A Hat in Time

Research on nostalgia has shown how media texts can promote ideological visions of the past. The 2017 3D platformer video game A Hat in Time (AHIT) is a case study in this nostalgic construction of values in a contemporary, postmodern, convergence-culture context. The game's marketing and text discursively and materially construct AHIT as a continuation of video games from the 1990s and early 2000s in a way that creates a communal nostalgia. Fans have also used the game itself as a platform by creating a library of more than five thousand modifications, or mods, many of which are based on 1990s and 2000s texts; these mods allow the game to serve as a platform for postmodern remixes of nostalgic texts. AHIT shows how contemporary convergence culture and media platforms allow for communal, customizable nostalgia

Thermal Management of Large Format Lithium Iron Phosphate Battery Pack for Electric Vehicle

Abstract not Available.</jats:p

Kayak Motors (semester?), IPRO 353

Our IPRO is aimed at laying the groundwork for a small company that supplies attachable, battery-powered motors for kayaks. Throughout the world, water sports are a popular activity for families and couples that look to spend time together while enriching their health. Recreational kayaking is a popular and convenient way for people to spend time with their family while engaged in an enjoyable activity. Due to imbalances in physical abilities within the family (such as the wife having to carry the paddling load when her husband gets tired), the pleasurable experience could become too rigorous for some individuals to enjoy. Our product is an easy-to-install kit that provides convenient, on-demand power assistance to enhance the kayaking experience.Deliverables for IPRO 353: Kayak Motors for the Fall 2005 semeste