Tehnoloogiainstituut

Permanent URI for this communityhttps://hdl.handle.net/10062/42114

Browse

Browsing Tehnoloogiainstituut by Author "Abner, Erik, juhendaja"

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Genome-wide association study for detecting autoimmune-disease-associated genetic pattern differences in specific HLA type carriers
    (Tartu Ülikool, 2023) Kukkonen, Arne; Abner, Erik, juhendaja
    The HLA locus variants are one of the strongest genetic predictors for most, if not all, human autoimmune diseases. The HLA locus genes include the antigen-presenting cell surface peptide encoding genes, which form an essential component in the maturation of the T-cell population in the thymus, and their subsequent activation in the periphery. Leveraging the modern population-wide genotype information that capture even the most polymorphic loci, this work sets the aim to design a case-control genome-wide association study (GWAS), that would result in the detection of non-HLA genetic variants that have a statistically different effect on an autoimmune disease in the carriers of certain HLA types, in comparison to the non-carriers. For the purpose of this aim, study groups are assembled based on specific HLA allele doses, so that for 42 HLA allele typesselected for this study there are 42 HLA-specific groups where every individual is a carrier of at least one copy of the HLA allele type. The effect sizes from the summary statistics of the HLA-specific GWASs are compared to a general population GWAS (which is done on all the participants of the Estonian Biobank in this case). The variants are considered relevant to this aim if their effect size is statisticallt different in the HLA-specific groups than they are in the general population GWAS.
  • Thumbnail Image
    Item
    Systematic interpretation of large-scale GWAS analyses of 5,035 phenotypes
    (Tartu Ülikool, 2024) Alekseienko, Anastasiia; Võsa, Urmo, juhendaja; Abner, Erik, juhendaja; Tartu Ülikool. Loodus- ja täppisteaduste valdkond; Tartu Ülikool. Tehnoloogiainstituut
    This thesis presents the systematic interpretation of 5,035 genome-wide association studies (GWAS) conducted within the Estonian Biobank, aiming to elucidate the genetic determinants influencing a diverse array of phenotypic traits. Through a review of existing literature and the application of advanced bioinformatic tools, the work done in this thesis outlined the results of main post-GWAS methods, such as the identification of novel variants, SNP heritability estimation, fine-mapping of causal variants, and prioritization of genes associated with complex traits. Around 26% of the variants identified as lead ones in this work are novel and had not been implicated by GWASs before. Fine mapping prioritized single genetic variants for 10.3% of investigated loci, providing hypotheses for further functional studies, and the gene prioritization approach identified the 2,402 lead variants to be related to 804 genes, several of those biologically interpretable. Heritability was reliably inferred for 25% of studied phenotypes, the most heritable traits being “Other specified hypothyroidism” (ICD-10 code E03.8), “Obesity due to excess calories” (E66.0), “Obesity” (E66), “Myopia” (H52.1), and “Hypertension” (I10). These findings are a good starting point for a more in-depth interpretation of loci associated with complex diseases in the Estonian Biobank.