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

TL;DR

This study finds DNA methylation patterns linked to inflammation in people with HIV, using a multi-trait approach to uncover new molecular insights.

Contribution

The study introduces a multi-trait EWAS approach to identify novel DNA methylation sites associated with inflammation in people with HIV.

Findings

Multi-trait EWAS identified 112 overlapping DNA methylation sites associated with inflammation not detected in single-trait analyses.

Top methylation sites were linked to genes like IFITM1, PARP9, and STAT1 involved in immune and viral response pathways.

The findings suggest molecular mechanisms underlying persistent inflammation in people with HIV.

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 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.

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