Genome-wide association study for detecting autoimmune-disease-associated genetic pattern differences in specific HLA type carriers



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Tartu Ülikool


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.



genome-wide association study, human leukocyte antigens, epistasis, autoimmune diseases