RT Journal Article
SR Electronic
T1 Pervasive additive and non-additive effects within the HLA region contribute to disease risk in the UK Biobank
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.28.119669
DO 10.1101/2020.05.28.119669
A1 Guhan Ram Venkataraman
A1 Julia Eve Olivieri
A1 Christopher DeBoever
A1 Yosuke Tanigawa
A1 Johanne Marie Justesen
A1 Alexander Dilthey
A1 Manuel A. Rivas
YR 2020
UL http://biorxiv.org/content/early/2020/06/12/2020.05.28.119669.abstract
AB The human leukocyte antigen (HLA) region is one of the most disease-associated regions of the human genome, yet even well-studied alleles in the HLA region have unknown impact on disease. Here, we study the effect of 156 HLA alleles on 677 binary phenotypes for 337,138 individuals in the UK Biobank. We assess HLA allele associations and subsequently use Bayesian Model Averaging for conditional analysis, a) replicating 88 known associations between HLA alleles and binary disease phenotypes such as cancer, and b) discovering 90 novel associations to phenotypes such as skin and reproductive tract cancers and to other phenotypes not previously associated with the HLA region (e.g. anemias and acne). We find several non-additive effects, suggesting a more complex landscape of disease-modifying effects throughout the region. Finally, we discover associations between homozygous HLA allele burden and several cancer and other phenotypes, suggesting that peptide presentation spectra as coded for by the HLA region are important in determining disease risk. Our results demonstrate the HLA region’s complexity and richness while underscoring its clinical relevance.Competing Interest StatementThe authors have declared no competing interest.