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
{"title":"A multi-trait epigenome-wide association study identified DNA methylation signature of inflammation among men with HIV.","authors":"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","doi":"10.1186/s13148-024-01763-2","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531128/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Epigenetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13148-024-01763-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
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.
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.