Narrative, genre and national myth in postmodern Canadian historical fiction

This thesis investigates the expansion and continuing proliferation of Canadian historical fiction during the past three decades, and makes a case for reading a number of these novels as postmodern historical fiction. Characterized by the postmodern tendency to problematize history and cross genre boundaries, the novels discussed here are nevertheless rooted in their Canadian context. To establish a theoretical framework, the thesis reviews the reconfiguration of history in contemporary critical theories and its impact on the writing of history and historical fiction, and investigates the debate over Canada's postcoloniality. In the textual analysis, I address the questions raised by the interaction between postmodern problematization of history and local concerns in the selected novels. What narrative strategies are employed to launch an epistemological and ontological questioning of history? Are alternative reconceptualizations of history offered after the problematization? How do these texts achieve genre transgression through narrative devices and what is the purpose of this? What meta-narratives of national history are challenged? What national myths are subverted and dismantled? Are some other myths accidentally reasserted in this deconstructive process? What effects does this historical revisionism or scepticism have on the understanding of Canadian national identity? The focus of the discussion is on the relationships between formal experimentation and thematic concerns and the ways these texts interweave general critiques of history and its representation with specific investigations into the Canadian context. Finally, I propose explanations for the flourishing of contemporary Canadian historical fiction by taking into account both the combined theoretical framework and the complexities and subtleties of the texts under scrutiny. The thesis concludes that the authors of these novels have complicated the postmodern questioning of history at a variety of levels and made that questioning accommodate the novelists' concern with Canadian specificities.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Narrative, genre and national myth in postmodern Canadian historical fiction

This thesis investigates the expansion and continuing proliferation of Canadian historical fiction during the past three decades, and makes a case for reading a number of these novels as postmodern historical fiction. Characterized by the postmodern tendency to problematize history and cross genre boundaries, the novels discussed here are nevertheless rooted in their Canadian context. To establish a theoretical framework, the thesis reviews the reconfiguration of history in contemporary critical theories and its impact on the writing of history and historical fiction, and investigates the debate over Canada's postcoloniality. In the textual analysis, I address the questions raised by the interaction between postmodern problematization of history and local concerns in the selected novels. What narrative strategies are employed to launch an epistemological and ontological questioning of history? Are alternative reconceptualizations of history offered after the problematization? How do these texts achieve genre transgression through narrative devices and what is the purpose of this? What meta-narratives of national history are challenged? What national myths are subverted and dismantled? Are some other myths accidentally reasserted in this deconstructive process? What effects does this historical revisionism or scepticism have on the understanding of Canadian national identity? The focus of the discussion is on the relationships between formal experimentation and thematic concerns and the ways these texts interweave general critiques of history and its representation with specific investigations into the Canadian context. Finally, I propose explanations for the flourishing of contemporary Canadian historical fiction by taking into account both the combined theoretical framework and the complexities and subtleties of the texts under scrutiny. The thesis concludes that the authors of these novels have complicated the postmodern questioning of history at a variety of levels and made that questioning accommodate the novelists' concern with Canadian specificities

Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome-wide association study.

Background and Aim: Chronic hepatitis C virus (HCV) infection, long-term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene-environment interactions in HCC. To address genetic susceptibility to HCC, we conducted a genome-wide association study (GWAS). Methods: Two case-control studies on HCC were conducted in the United States. DNA samples were genotyped using the Illumian microarray chip with over 710 000 single nucleotide polymorphisms (SNPs). We compared these SNPs between 705 HCC cases and 1455 population controls for their associations with HCC and verified our findings in additional studies. Results: In this GWAS, we found that two SNPs were associated with HCC at Conclusions: SNPs i

Genome-Wide Meta-Analysis of Five Asian Cohorts Identifies PDGFRA as a Susceptibility Locus for Corneal Astigmatism

Corneal astigmatism refers to refractive abnormalities and irregularities in the curvature of the cornea, and this interferes with light being accurately focused at a single point in the eye. This ametropic condition is highly prevalent, influences visual acuity, and is a highly heritable trait. There is currently a paucity of research in the genetic etiology of corneal astigmatism. Here we report the results from five genome-wide association studies of corneal astigmatism across three Asian populations, with an initial discovery set of 4,254 Chinese and Malay individuals consisting of 2,249 cases and 2,005 controls. Replication was obtained from three surveys comprising of 2,139 Indians, an additional 929 Chinese children, and an independent 397 Chinese family trios. Variants in PDGFRA on chromosome 4q12 (lead SNP: rs7677751, allelic odds ratio = 1.26 (95% CI: 1.16–1.36), Pmeta = 7.87×10−9) were identified to be significantly associated with corneal astigmatism, exhibiting consistent effect sizes across all five cohorts. This highlights the potential role of variants in PDGFRA in the genetic etiology of corneal astigmatism across diverse Asian populations

Polygenic risk scores for prediction of breast cancer risk in Asian populations.

PURPOSE: Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups. METHODS: The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases). RESULTS: The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk. CONCLUSION: PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry

A common variant near TGFBR3 is associated with primary open angle glaucoma

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis

Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia : The CREAM Consortium

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).Peer reviewe