Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
Results
Showing 1 to 20 of 38 for “"Causal Variants"”.
-
Using molecular QTLs to identify cell types and causal variants for complex traits
… traits, and yet for most associated loci the causal variants and molecular mechanisms remain unknown. Studies mapping quantitative trait loci (QTLs) for molecular phenotypes, such as gene expression, RNA splicing, and chromatin accessibility, provide rich data that can link variant effects in …
-
Statistical Techniques to Fine Map the Related Genetic Aetiology of Autoimmune Diseases
… these studies and enable the analysis of the causal variants of these diseases. Colocalization methods disentangle whether potential causal variants are shared or distinct in related diseases, and enable the discovery of novel associations below the single-trait significance threshold. …
-
Computational personal genomics : understanding the functional effects of sequence variation
… analyzing functional data to identify putative causal variants in eQTLs or GWAS loci. We show that these approaches improve upon existing methods. We observe that there are genome-wide correlations in allele-specific activity, and that allele-specific activity is widespread across the autosomes. …
-
Allele-Specic QTL fine-mapping with PLASMA
… detection of quantitative trait loci (QTLs) with causal effects on molecular traits. In simulations, PLASMA accurately prioritizes causal QTL variants over a wide range of genetic architectures. Applied to RNA-Seq data from 524 kidney tumor samples, PLASMA achieves a greater power at 50 samples …
-
Statistical methods to improve understanding of the genetic basis of complex diseases
… with the aim of deducing the specific sequence variants that are causal for the disease of interest. Functional genomic data is now routinely generated from high-throughput experiments. This data can reveal clues relating to disease biology, for example elucidating the functional genomic …
-
Regulation of gene expression in macrophage immune response
… into the functions of disease-associated variants. However, many eQTLs are cell type and context specific. This is particularly relevant for immune cells, whose cellular function and behaviour can be substantially altered by external cues. Furthermore, understanding mechanisms behind eQTLs …
-
Integrative statistical methods for the genomic analysis of immune-mediated disease
… disease phenotypes. However, elucidating the causal mechanisms underlying such associations has proved challenging due to the regulatory nature of the majority of signals. In Chapters 2 and 3, I hypothesised that promoter-capture Hi-C (PCHi-C) data might have utility in physically linking …
-
Primary biliary cholangitis: genetic risk, phenotypic stratification and disease pathogenesis
… than sixty risk loci for the disease. Candidate variants and genes have been proposed at these risk loci. However, there are limitations in interpreting these candidate variants and genes. This impedes efforts to translate genetic observations into novel therapies. Many of these risk loci for PBC …
-
Investigating the Role of Inflammatory Biomarkers and Incretins in the Aetiology of Type 2 Diabetes and Coronary Heart Disease using Human Genetics
… diseases. Aims: To investigate the potential causal roles of IL-6 and GIP receptor signalling for the risk of cardiometabolic diseases, specifically T2D and coronary heart disease (CHD), through analysis of large-scale genetic data from patient and population-based studies. Methods: 1) …
-
Uncovering Functional Alzheimer’s Disease Variants and Their Effector Genes through Single-Cell CRISPRi Screening and 3D Genomics
… studies (GWAS) have successfully linked variants to traits in complex human diseases, functional dissection of the discovered loci has lagged behind. We address this gap in the context of Alzheimer’s disease (AD) by performing variant-to-gene (V2G) mapping to implicate causal variants and …
-
Genetics of hearing impairment and peripheral neuropathy in Mali
… SSA populations for which the prevalence of HI-causal variants is insignificant. Charcot-Marie-Tooth disease (CMT), is the most common inherited peripheral neuropathy (IPN) with a high clinical and genetic heterogeneity and over 100 genes are related to CMT, mostly in populations of Caucasian …
-
Primary sclerosing cholangitis: from genetic risk to disease biology
… opportunity to understand the underlying causal biology of disease. This is because the genetic variants associated with disease susceptibility perturb genes and biological pathways that contribute to disease causality. Twenty-two regions of the genome, outside of the HLA, have been …
-
Uncovering the variability, regulatory roles and mutation rates of short tandem repeats
… human genome, STRs have been identified as the causal variants in diseases such as Fragile X syndrome and Huntington's disease. However, in spite of their potentially profound biological consequences, STRs remain systematically understudied due to difficulties associated with obtaining accurate …
-
Medaka fish as a model for complex trait genetics
… Association Studies (GWAS), and post-GWAS causal variant prioritisation. In Chapter 3, I investigate heart rate in medaka embryos— a phenotype relevant to human physiology— and its variation across inbred strains exposed to different temperatures. In collaboration with Dr. Bettina Welz (BW, …
-
The Molecular Mechanism Of The Gwas Association Of The Slc22a1 Locus With Metabolic Traits
… the molecular mechanism by which SLC22A1 and its variants alter plasma acylcarnitine and LDL cholesterol levels. To study the hepatic function of SLC22A1, we generated liver-specific knockout or overexpression mouse models of SLC22A1 and closely examined their acylcarnitine and lipid profiles. We …
-
Functional Investigation of Genetic Determinants of Red Blood Cell Traits
… identification and interpretation of candidate causal variants and genes remain challenging. With increasing power to detect genetic associations, many loci reveal multiple statistically independent signals, which - while further adding complexity - also include rare variants with large effect …
-
Identification of Deleterious and Disease Alleles in a General Population and Preterm Labor Patients
… data to predict underlying disease-causing variants.</p> <p>To address the first question, I developed a new likelihood ratio test for sequence conservation to predict deleterious missense alleles in the human genome. By applying the new test to three personal genomes, I find that the …
-
Investigating the genomic distribution and potential contribution of retrotransposable elements in relation to their potential impact on genome function and predisposition to human diseases.
… have only recently begun incorporating RTE variants (RTEV) in association with complex human diseases. This study aimed to investigate the impact of RTEs activity on GF and the potential association of RTEV with disease susceptibility. A comprehensive database of all non-reference L1s, Alus, …
-
Characterization of 𝘈𝘵𝘩𝘴𝘲1, an Atherosclerosis Modifier Locus on Mouse Chromosome 4:
… in humans have identified multiple genetic variants associated with atherosclerosis related traits- such as circulating lipid levels and hypertension- as well as myocardial infarction and stroke, few of the causal variants or underlying mechanisms are known. The work presented in this thesis …
-
The functional impact of copy number variation in the human genome
… technologies, our ability to discover genetic variants is running far ahead of our ability to interpret their functional impact. One approach to close this gap is to explore statistical association between genetic variants and phenotypes. In contrast to the successes of genome-wide association …
Page 1 of 2