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

IF 4.8 2区 医学 Q1 GENETICS & HEREDITY Clinical Epigenetics Pub Date : 2024-11-02 DOI:10.1186/s13148-024-01763-2
Junyu Chen, Qin Hui, Boghuma K Titanji, Kaku So-Armah, Matthew Freiberg, Amy C Justice, Ke Xu, Xiaofeng Zhu, Marta Gwinn, Vincent C Marconi, Yan V Sun
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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.

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一项多特征全表观基因组关联研究发现了感染艾滋病毒男性的 DNA 甲基化炎症特征。
炎症是导致艾滋病病毒感染者(PWH)发病率和死亡率过高的许多病症的根源。一些单性状全表观基因组关联研究(EWAS)表明,炎症与艾滋病病毒感染者的 DNA 甲基化(DNAm)有关。多性状全表观遗传关联研究可进一步提高统计能力,并揭示不同炎症标志物之间的共同途径。我们在退伍军人老龄队列研究(n = 920)中对三种炎症标记物(可溶性 CD14、D-二聚体和白细胞介素-6)进行了单特质 EWAS 分析。研究对象均为男性退伍军人,平均年龄为 51 岁,82.3% 的人自称为黑人。然后,我们采用了两种多性状 EWAS 方法--CPASSOC 和 OmniTest,将单性状 EWAS 结果结合起来。CPASSOC 和 OmniTest 分别确定了 189 个和 157 个炎症相关 DNAm 位点,其中 112 个位点重叠。在鉴定出的位点中,56%在任何单一性状EWAS中都不显著。顶级位点被映射到炎症相关基因上,包括 IFITM1、PARP9 和 STAT1。这些基因在 "I型干扰素信号 "和 "对病毒的免疫反应 "等通路中明显富集。我们的研究表明,多性状 EWAS 可以改进炎症相关 DNAm 位点、基因和通路的发现。这些DNAm位点可能是解决PWH持续炎症的关键。
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来源期刊
自引率
5.30%
发文量
150
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
期刊最新文献
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