Boghuma K Titanji1, Zeyuan Wang2, Junyu Chen2, Qin Hui2, Kaku So-Armah3, Matthew Freiberg4, Amy C Justice5,6, Xu Ke5,6, Vincent C Marconi1,7,8,9, Yan V Sun2,7. 1. Division of Infectious Diseases, Emory University School of Medicine. 2. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA. 3. Boston University Medical School, MA. 4. Cardiovascular Medicine Division and Tennessee Valley Healthcare System, Vanderbilt University Medical Center, Nashville, TN. 5. Yale University School of Medicine, New Haven. 6. Connecticut Veteran Health System, West Haven, CT. 7. Atlanta Veterans Affairs Healthcare System, Decatur. 8. Hubert Department of Global Health, Rollins School of Public Health. 9. Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Abstract
OBJECTIVES: Elevated plasma levels of sCD14 predict all-cause mortality in people with HIV (PWH). Epigenetic regulation plays a key role in infection and inflammation. To reveal the epigenetic relationships between sCD14, immune function and disease progression among PWH, we conducted an epigenome-wide association study (EWAS) of sCD14 and investigated the relationship with mortality. DESIGN AND METHODS: DNA methylation (DNAm) levels of peripheral blood samples from PWH in the Veterans Aging Cohort Study (VACS) were measured using the Illumina Infinium Methylation 450K (n = 549) and EPIC (850K) BeadChip (n = 526). Adjusted for covariates and multiple testing, we conducted an epigenome-wide discovery, replication, and meta-analysis to identify significant associations with sCD14. We then examined and replicated the relationship between the principal epigenetic sites and survival using Cox regression models. FINDINGS: We identified 118 DNAm sites significantly associated with sCD14 in the meta-analysis of 1075 PWH. The principal associated DNAm sites mapped to genes (e.g. STAT1, PARP9, IFITM1, MX1, and IFIT1) related to inflammation and antiviral response. Adjusting for multiple testing, 10 of 118 sCD14-associated DNAm sites significantly predicted survival time conditional on sCD14 levels. CONCLUSION: The identification of DNAm sites independently predicting survival may improve our understanding of prognosis and potential therapeutic targets among PWH.
OBJECTIVES: Elevated plasma levels of sCD14 predict all-cause mortality in people with HIV (PWH). Epigenetic regulation plays a key role in infection and inflammation. To reveal the epigenetic relationships between sCD14, immune function and disease progression among PWH, we conducted an epigenome-wide association study (EWAS) of sCD14 and investigated the relationship with mortality. DESIGN AND METHODS: DNA methylation (DNAm) levels of peripheral blood samples from PWH in the Veterans Aging Cohort Study (VACS) were measured using the Illumina Infinium Methylation 450K (n = 549) and EPIC (850K) BeadChip (n = 526). Adjusted for covariates and multiple testing, we conducted an epigenome-wide discovery, replication, and meta-analysis to identify significant associations with sCD14. We then examined and replicated the relationship between the principal epigenetic sites and survival using Cox regression models. FINDINGS: We identified 118 DNAm sites significantly associated with sCD14 in the meta-analysis of 1075 PWH. The principal associated DNAm sites mapped to genes (e.g. STAT1, PARP9, IFITM1, MX1, and IFIT1) related to inflammation and antiviral response. Adjusting for multiple testing, 10 of 118 sCD14-associated DNAm sites significantly predicted survival time conditional on sCD14 levels. CONCLUSION: The identification of DNAm sites independently predicting survival may improve our understanding of prognosis and potential therapeutic targets among PWH.
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