Genome-wide association study for detecting autoimmune-disease-associated genetic pattern differences in specific HLA type carriers
Date
2023
Authors
Journal Title
Journal ISSN
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Publisher
Tartu Ülikool
Abstract
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.
Description
Keywords
genome-wide association study, human leukocyte antigens, epistasis, autoimmune diseases