title: A PheWAS approach in studying HLA-DRB1*1501.
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.
authors: Department of Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA. hebbring.scott@mcrf.mfldclin.edu
authors: S J
authors: SJ
authors: Hebbring
authors: S J
authors: SJ
authors: Schrodi
authors: Z
authors: Z
authors: Ye
authors: Z
authors: Z
authors: Zhou
authors: D
authors: D
authors: Page
authors: M H
authors: MH
authors: Brilliant
mesh_terms: D004890:Erythema / Q000235:genetics; D005240:Feasibility Studies; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D038801:International Classification of Diseases; D008108:Liver Diseases, Alcoholic / Q000235:genetics; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results
chemical_list: D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen
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