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

A PheWAS approach in studying HLA-DRB1*1501

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A PheWAS approach in studying HLA-DRB1*1501

S J Hebbring et al. Genes Immun. 2013 Apr.

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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Conflict of interest statement

CONFLICT OF INTEREST

Authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Manhattan plot of unadjusted −log10 (P-values) for all ICD9 and V codes as related to rs3135388 genotype. Highlighted are associations results for multiple sclerosis (MS) (ICD9 340, P=0.023), erythematous conditions (ICD9 695, P=0.0054), and alcohol-induced cirrhosis of liver (ICD9 571.2, P=0.00011). Grey diamonds represent ICD9 codes defined by “rule of 1,” while black squares represent phenotypes defined by “rule of 2.”

References

    1. 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]
    1. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461:747–753. - PMC - PubMed
    1. Lango Allen H, Estrada K, Lettre G, Berndt SI, Weedon MN, Rivadeneira F, et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature. 1021;467:832–838. - PMC - PubMed
    1. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447:661–678. - PMC - PubMed
    1. 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

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