What has GWAS done for HLA and disease associations?

Summary
The major histocompatibility complex (MHC) is located in chromosome 6p21 and contains crucial regulators of immune response, including human leucocyte antigen (HLA) genes, alongside other genes with nonimmunological roles. More recently, a repertoire of noncoding RNA genes, including expressed pseudogenes, has also been identified. The MHC is the most gene dense and most polymorphic part of the human genome. The region exhibits haplotype‐specific linkage disequilibrium patterns, contains the strongest cis‐ and trans‐eQTLs/meQTLs in the genome and is known as a hot spot for disease associations. Another layer of complexity is provided to the region by the extreme structural variation and copy number variations. While the HLA‐B gene has the highest number of alleles, the HLA‐DR/DQ subregion is structurally most variable and shows the highest number of disease associations. Reliance on a single reference sequence has complicated the design, execution and analysis of GWAS for the MHC region and not infrequently, the MHC region has even been excluded from the analysis of GWAS data. Here, we contrast features of the MHC region with the rest of the genome and highlight its complexities, including its functional polymorphisms beyond those determined by single nucleotide polymorphisms or single amino acid residues. One of the several issues with customary GWAS analysis is that it does not address this additional layer of polymorphisms unique to the MHC region. We hig...

Source: International Journal of Immunogenetics - September 6, 2017 Category: Genetics & Stem Cells Authors: A. E. Kennedy, U. Ozbek, M. T. Dorak Tags: Review Source Type: research