Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22 981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10-8). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine.
Bibliographical noteFunding Information:
We are grateful to all the participants of the eMERGE study. This study was supported by the following U01 grants from the National Human Genome Research Institute (NHGRI), a component of the National Institutes of Health (NIH), Bethesda, MD, USA: (1) U01HG006375 (Group Health/University of Washington); (2) U01HG006382 (Geisinger Health System); (3) U01HG006379 (Mayo Clinic); (4) U01HG006389 (Essentia Health and Marshfield Clinic Research Foundation); (5) U01HG006388 (Northwestern University); (6) HG004438 (Center for Inherited Disease Research, Johns Hopkins University); (7) HG004424 (Broad Institute of Harvard and MIT); (8) U01HG006378, U01HG006385, U01HG006385 (Vanderbilt University); (9) U01HG006380 (The Mt Sinai Hospital); (10) U01HG006828 (Cincinnati Children’s Hospital Medical Center/Harvard); and (11) U01HG006830 (Children’s Hospital of Philadelphia). Additional support was provided by a State of Washington Life Sciences Discovery Fund award to the Northwest Institute of Genetic Medicine (to GPJ).