A PheWAS approach in studying HLA-DRB1*1501
- PMID: 23392276
- PMCID: PMC3637423
- DOI: 10.1038/gene.2013.2
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.
Conflict of interest statement
Authors declare no conflicts of interest.
Figures

References
-
- Hindorff LA, MacArthur J, Wise A, Junkins HA, Hall PN, Klemm AK, et al. A Catalog of Published Genome-Wide Association Studies. 2012 Available at: www.genome.gov/gwastudies. [cited 2012]
-
- Freudenberg J, Lee HS, Han BG, Shin HD, Kang YM, Sung YK, et al. Genome-wide association study of rheumatoid arthritis in Koreans: population-specific loci as well as overlap with European susceptibility loci. Arthritis Rheum. 2011;63:884–893. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials