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

Jason H. Karnes(University of Arizona), Lisa Bastarache(Vanderbilt University), Christian M. Shaffer(Vanderbilt University), Silvana Gaudieri(Murdoch University), Yaomin Xu(Vanderbilt University), Andrew M. Glazer(Vanderbilt University), Jonathan D. Mosley(Vanderbilt University), Shilin Zhao(Vanderbilt University), Soumya Raychaudhuri(Broad Institute), S. Mallal(Murdoch University), Zhan Ye(Marshfield Clinic), John Mayer(Marshfield Clinic), Murray H. Brilliant(Marshfield Clinic), Scott J. Hebbring(Marshfield Clinic), Dan M. Roden(Vanderbilt University), Elizabeth J. Phillips(Vanderbilt University), Joshua C. Denny(Vanderbilt University)
Science Translational Medicine
May 10, 2017
Cited by 130Open Access
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Abstract

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.


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