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

Jason H. Karnes, Lisa Bastarache, Christian M. Shaffer, Silvana Gaudieri, Yaomin Xu, Andrew M. Glazer, Jonathan D. Mosley, Shilin Zhao, Soumya Raychaudhuri, Simon Mallal, Zhan Ye, John G. Mayer, Murray H. Brilliant, Scott J. Hebbring, Dan M. Roden, Elizabeth J. Phillips, Joshua C. Denny

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


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. 2017

Original languageEnglish (US)
Article numberaai8708
JournalScience translational medicine
Issue number389
StatePublished - May 10 2017

ASJC Scopus subject areas

  • Medicine(all)


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