%0 Journal Article
%T A multi-trait epigenome-wide association study identified DNA methylation signature of inflammation among people with HIV.
%A Chen J
%A Hui Q
%A Titanji BK
%A So-Armah K
%A Freiberg M
%A Justice AC
%A Xu K
%A Zhu X
%A Gwinn M
%A Marconi VC
%A Sun YV
%J Res Sq
%V 0
%N 0
%D 2024 May 31
%M 38854093
暂无%R 10.21203/rs.3.rs-4419840/v1
%X 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 Veteran 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 suggest molecular mechanisms in response to inflammation associated with HIV and might hold the key to addressing persistent inflammation in PWH.