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A PheWAS approach in studying HLA-DRB1*1501

Genes & Immunity volume 14, pages 187–191 (2013)Cite this article

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Abstract

HLA-DRB1 codes for a major histocompatibility complex class II cell surface receptor. Genetic variants in and around this gene have been linked to numerous autoimmune diseases. Most notably, an association between HLA-DRB1*1501 haplotype and multiple sclerosis (MS) has been defined. Utilizing electronic health records and 4235 individuals within Marshfield Clinic’s Personalized Medicine Research Project, a reverse genetic screen coined phenome-wide association study (PheWAS) tested association of rs3135388 genotype (tagging HLA-DRB1*1501) with 4841 phenotypes. As expected, HLA-DRB1*1501 was associated with MS (International Classification of Disease version 9-CM (ICD9) 340, P=0.023), whereas the strongest association was with alcohol-induced cirrhosis of the liver (ICD9 571.2, P=0.00011). HLA-DRB1*1501 also demonstrated association with erythematous conditions (ICD9 695, P=0.0054) and benign neoplasms of the respiratory and intrathoracic organs (ICD9 212, P=0.042), replicating previous findings. This study not only builds on the feasibility/utility of the PheWAS approach, represents the first external validation of a PheWAS, but may also demonstrate the complex etiologies associated with the HLA-DRB1*1501 loci.

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Acknowledgements

This study was funded by NLM grant 5T15LM007359, NIGMS grant R01GM097618, NCATS grant UL1TR000427 and NCRR grant 1U1RR025011. In addition, the authors gratefully acknowledge the support from the Marshfield Clinic Research Foundation through the Personalized Medicine Research Project.

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Authors and Affiliations

  1. Department of Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA

    S J Hebbring, S J Schrodi & M H Brilliant

  2. Department of Computation and Informatics in Biology and Medicine, University of Wisconsin Madison, Madison, WI, USA

    S J Hebbring & D Page

  3. Department of Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI, USA

    Z Ye & Z Zhou

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  1. S J Hebbring
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Correspondence to S J Hebbring.

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Hebbring, S., Schrodi, S., Ye, Z. et al. A PheWAS approach in studying HLA-DRB1*1501. Genes Immun 14, 187–191 (2013). https://doi.org/10.1038/gene.2013.2

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