Genome-wide association study (GWAS) of human host factors influencing viral severity of herpes simplex virus type 2 (HSV-2)

Herpes simplex virus type 2 (HSV-2) is an incurable viral infection with severity ranging from asymptomatic to frequent recurrences. The viral shedding rate has been shown as a reproducible HSV-2 severity endpoint that correlates with lesion rates. We used a genome-wide association study (GWAS) to investigate the role of common human genetic variation in HSV-2 severity. We performed a GWAS on 223 HSV-2-positive participants of European ancestry. Severity was measured by viral shedding rate, as defined by the percent of days PCR+ for HSV-2 DNA over at least 30 days. Analyses were performed under linear regression models, adjusted for age, sex, and ancestry. There were no genome-wide significant (p<5E-08) associations with HSV-2 viral shedding rate. The top non-significant SNP (rs75932292, p=6.77E-08) associated with HSV-2 viral shedding was intergenic, with the nearest known biologically interesting gene (ABCA1) ∼130Kbp downstream. Several other SNPs approaching significance were in or near genes with viral or neurological associations, including 4 SNPs in KIF1B. The current study is the first comprehensive genome-wide investigation of human genetic variation in virologic severity of established HSV-2 infection. However, no significant associations were observed with HSV-2 virologic severity, leaving the exact role of human variation in HSV-2 severity unclear.