A PheWAS approach in studying HLA-DRB1*1501
By S. Hebbring, Steven J. Schrodi, Zhan Ye, Zhiyi Zhou, D. Page, M. Brilliant. 2013
83 citations recorded by the source corpus.
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.
Subfields: Genetics, Immunology, Radiology, Nuclear Medicine and Imaging
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In Genetics
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In Immunology
Citations in the corpus
- Natural Language Processing for EHR-Based Computational Phenotyping (2018, background): “WAS to detect genetic association [72], [73], [74].”
- Semi-Supervised Learning of the Electronic Health Record for Phenotype Stratification (2016, background): “Despite this, EHRs have already proven an effective source of phenotypes in genetic association studies [3,4].”
- Extracting research-quality phenotypes from electronic health records to support precision medicine (2015, background): “Hebbring and coworkers replicated a novel PheWAS finding of an association between the human leukocyte antigen HLA-DRB1*1501 variant and erythematous rashes in the Marshfield Clinic biobank [100] and have subsequently leveraged this cohort to study functional variants across the genome [101].”