Murdoch University Research Repository

Welcome to the Murdoch University Research Repository

The Murdoch University Research Repository is an open access digital collection of research
created by Murdoch University staff, researchers and postgraduate students.

Learn more

Phenome-wide scanning identifies multiple diseases and disease severity phenotypes associated with HLA variants

Karnes, J.H., Bastarache, L., Shaffer, C.M., Gaudieri, S., Xu, Y., Glazer, A.M., Mosley, J.D., Zhao, S., Raychaudhuri, S., Mallal, S., Ye, Z., Mayer, J.G., Brilliant, M.H., Hebbring, S.J., Roden, D.M., Phillips, E.J. and Denny, J.C. (2017) Phenome-wide scanning identifies multiple diseases and disease severity phenotypes associated with HLA variants. Science Translational Medicine, 9 (389). eaai8708.

Link to Published Version:
*Subscription may be required


Although many phenotypes have been associated with variants in human leukocyte antigen (HLA) genes, the full phenotypic impact of HLA variants across all diseases is unknown. We imputed HLA genomic variation from two populations of 28,839 and 8431 European ancestry individuals and tested association of HLA variation with 1368 phenotypes. A total of 104 four-digit and 92 two-digit HLA allele phenotype associations were significant in both discovery and replication cohorts, the strongest being HLA-DQB1*03:02 and type 1 diabetes. Four previously unidentified associations were identified across the spectrum of disease with two- and four-digit HLA alleles and 10 with nonsynonymous variants. Some conditions associated with multiple HLA variants and stronger associations with more severe disease manifestations were identified. A comprehensive, publicly available catalog of clinical phenotypes associated with HLA variation is provided. Examining HLA variant disease associations in this large data set allows comprehensive definition of disease associations to drive further mechanistic insights.

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Copyright: © 2017, American Association for the Advancement of Science
Item Control Page Item Control Page