Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 2;16(1):152.
doi: 10.1186/s13148-024-01763-2.

A multi-trait epigenome-wide association study identified DNA methylation signature of inflammation among men with HIV

Junyu Chen  1 , Qin Hui  1 , Boghuma K Titanji  2 , Kaku So-Armah  3 , Matthew Freiberg  4 , Amy C Justice  5   6 , Ke Xu  5   7 , Xiaofeng Zhu  8 , Marta Gwinn  1 , Vincent C Marconi  2   9   10 , Yan V Sun  11   12
Affiliations

A multi-trait epigenome-wide association study identified DNA methylation signature of inflammation among men with HIV

Junyu Chen et al. Clin Epigenetics. .

Abstract

Inflammation underlies many conditions causing excess morbidity and mortality among people with HIV (PWH). A handful of single-trait epigenome-wide association studies (EWAS) have suggested that inflammation is associated with DNA methylation (DNAm) among PWH. Multi-trait EWAS may further improve statistical power and reveal pathways in common between different inflammatory markers. We conducted single-trait EWAS of three inflammatory markers (soluble CD14, D-dimers and interleukin-6) in the Veterans Aging Cohort Study (n = 920). The study population was all male PWH with an average age of 51 years, and 82.3% self-reported as Black. We then applied two multi-trait EWAS methods-CPASSOC and OmniTest-to combine single-trait EWAS results. CPASSOC and OmniTest identified 189 and 157 inflammation-associated DNAm sites, respectively, of which 112 overlapped. Among the identified sites, 56% were not significant in any single-trait EWAS. Top sites were mapped to inflammation-related genes including IFITM1, PARP9 and STAT1. These genes were significantly enriched in pathways such as "type I interferon signaling" and "immune response to virus." We demonstrate that multi-trait EWAS can improve the discovery of inflammation-associated DNAm sites, genes and pathways. These DNAm sites might hold the key to addressing persistent inflammation in PWH.

Keywords: D-dimer; EWAS; HIV; IL-6; sCD14.

PubMed Disclaimer

Conflict of interest statement

V.C.M. has received investigator-initiated research grants (to the institution) and consultation fees from Eli Lilly, Bayer, Gilead Sciences, Merck and ViiV.

Figures

Fig. 1
Fig. 1
Outline of multi-trait epigenome-wide associations studies of inflammatory markers in the Veterans Aging Cohort Study (VACS)
Fig. 2
Fig. 2
Overlapping CpG sites identified by the cross-phenotype association test (CPASSOC) and the omnibus test (OMNITEST) in meta-analyses
Fig. 3
Fig. 3
Comparison between the beta-coefficients of the CpG sites associated with (A) IL-6, (B) sCD14 and (C) D-dimer in VACS and the ones associated with C-reactive protein in the general population
See this image and copyright information in PMC

Update of

References

    1. Forsythe SS, McGreevey W, Whiteside A, et al. Twenty years of antiretroviral therapy for people living with HIV: global costs, health achievements economic benefits. Health Aff. 2019;38(7):1163–72. 10.1377/hlthaff.2018.05391. - PubMed
    1. Roomaney RA, van Wyk B, Pillay-van VW. Aging with HIV: increased risk of HIV comorbidities in older adults. Int J Environ Res Public Health. 2022;19(4):2359. 10.3390/ijerph19042359. - PMC - PubMed
    1. So-Armah KA, Tate JP, Chang CH, et al. Do biomarkers of inflammation, monocyte activation, and altered coagulation explain excess mortality between HIV infected and uninfected people? J Acquir Immune Defic Syndr (1999). 2016;72(2):206–13. 10.1097/qai.0000000000000954. - PMC - PubMed
    1. Borges ÁH, O’Connor JL, Phillips AN, et al. Interleukin 6 is a stronger predictor of clinical events than high-sensitivity C-reactive protein or D-dimer during HIV infection. J Infect Dis. 2016;214(3):408–16. 10.1093/infdis/jiw173. - PMC - PubMed
    1. Peterson TE, Baker JV. Assessing inflammation and its role in comorbidities among persons living with HIV. Curr Opin Infect Dis. 2019;32(1):8–15. 10.1097/qco.0000000000000510. - PubMed