A PheWAS approach in studying HLA-DRB1*1501

Genes Immun. 2013 Apr;14(3):187-91. doi: 10.1038/gene.2013.2. Epub 2013 Feb 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Erythema / genetics
  • Feasibility Studies
  • Genetic Association Studies / methods*
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • HLA-DRB1 Chains / genetics*
  • Haplotypes
  • Humans
  • International Classification of Diseases
  • Liver Diseases, Alcoholic / genetics
  • Middle Aged
  • Multiple Sclerosis / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Reproducibility of Results


  • HLA-DRB1 Chains
  • HLA-DRB1*15:01 antigen