TY - JOUR
T1 - Phenome-wide scanning identifies multiple diseases and disease severity phenotypes associated with HLA variants
AU - Karnes, Jason H.
AU - Bastarache, Lisa
AU - Shaffer, Christian M.
AU - Gaudieri, Silvana
AU - Xu, Yaomin
AU - Glazer, Andrew M.
AU - Mosley, Jonathan D.
AU - Zhao, Shilin
AU - Raychaudhuri, Soumya
AU - Mallal, Simon
AU - Ye, Zhan
AU - Mayer, John G.
AU - Brilliant, Murray H.
AU - Hebbring, Scott J.
AU - Roden, Dan M.
AU - Phillips, Elizabeth J.
AU - Denny, Joshua C.
PY - 2017/5/10
Y1 - 2017/5/10
N2 - 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
AB - 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
UR - http://www.scopus.com/inward/record.url?scp=85019257454&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.aai8708
DO - 10.1126/scitranslmed.aai8708
M3 - Article
C2 - 28490672
AN - SCOPUS:85019257454
SN - 1946-6234
VL - 9
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 389
M1 - aai8708
ER -
