{"title":"Association between DNA methylation predicted growth differentiation factor 15 and mortality: results from NHANES 1999–2002","authors":"Honglian Luo, Yun Shen","doi":"10.1007/s40520-024-02896-3","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Growth differentiation factor 15 (GDF15) is a crucial biomarker in various physiological and pathological processes. While elevated GDF15 levels are linked to increased mortality risk, the role of DNA methylation (DNAm)-predicted GDF15 in predicting mortality has not been extensively studied. The purpose of the study is to investigate the association between DNAm-predicted GDF15 levels and all-cause and cardiovascular disease (CVD) mortality in a nationally representative cohort.</p><h3>Methods</h3><p>Data from NHANES 1999–2002 were analyzed. DNAm-predicted GDF15 levels were estimated using a regression model. Weighted multivariate Cox regressions were employed to assess the relationship between DNAm-predicted GDF15 and mortality outcomes. Restricted cubic splines were used to explore dose-response relationships, and subgroup analyses were conducted to enhance result reliability.</p><h3>Results</h3><p>Higher DNAm-predicted GDF15 levels were significantly associated with increased all-cause mortality risk (HR = 1.08, 95% CI: 1.02–1.15). Participants in the highest DNAm-predicted GDF15 tertile showed significantly higher all-cause mortality risk (HR = 1.56, 95% CI: 1.16–2.10) and a 2.52-fold increased risk of cardiovascular mortality (HR = 2.52, 95% CI: 1.22–5.19). Kaplan-Meier curves revealed decreasing survival probability with higher DNAm-predicted GDF15 tertiles. Restricted cubic spline analysis demonstrated a non-linear dose-response relationship between DNAm-predicted GDF15 levels and cardiovascular mortality. The positive correlation between DNAm-predicted GDF15 and mortality remained robust in most of subgroups.</p><h3>Conclusions</h3><p>DNAm-predicted GDF15 independently predicts all-cause and cardiovascular mortality. This association persists across multiple models and stratified subgroups, supporting GDF15’s value as a biomarker for mortality risk stratification. Future research should elucidate underlying biological mechanisms and evaluate GDF15’s clinical utility in guiding mortality risk reduction interventions.</p></div>","PeriodicalId":7720,"journal":{"name":"Aging Clinical and Experimental Research","volume":"36 1","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40520-024-02896-3.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging Clinical and Experimental Research","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s40520-024-02896-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Growth differentiation factor 15 (GDF15) is a crucial biomarker in various physiological and pathological processes. While elevated GDF15 levels are linked to increased mortality risk, the role of DNA methylation (DNAm)-predicted GDF15 in predicting mortality has not been extensively studied. The purpose of the study is to investigate the association between DNAm-predicted GDF15 levels and all-cause and cardiovascular disease (CVD) mortality in a nationally representative cohort.
Methods
Data from NHANES 1999–2002 were analyzed. DNAm-predicted GDF15 levels were estimated using a regression model. Weighted multivariate Cox regressions were employed to assess the relationship between DNAm-predicted GDF15 and mortality outcomes. Restricted cubic splines were used to explore dose-response relationships, and subgroup analyses were conducted to enhance result reliability.
Results
Higher DNAm-predicted GDF15 levels were significantly associated with increased all-cause mortality risk (HR = 1.08, 95% CI: 1.02–1.15). Participants in the highest DNAm-predicted GDF15 tertile showed significantly higher all-cause mortality risk (HR = 1.56, 95% CI: 1.16–2.10) and a 2.52-fold increased risk of cardiovascular mortality (HR = 2.52, 95% CI: 1.22–5.19). Kaplan-Meier curves revealed decreasing survival probability with higher DNAm-predicted GDF15 tertiles. Restricted cubic spline analysis demonstrated a non-linear dose-response relationship between DNAm-predicted GDF15 levels and cardiovascular mortality. The positive correlation between DNAm-predicted GDF15 and mortality remained robust in most of subgroups.
Conclusions
DNAm-predicted GDF15 independently predicts all-cause and cardiovascular mortality. This association persists across multiple models and stratified subgroups, supporting GDF15’s value as a biomarker for mortality risk stratification. Future research should elucidate underlying biological mechanisms and evaluate GDF15’s clinical utility in guiding mortality risk reduction interventions.
期刊介绍:
Aging clinical and experimental research offers a multidisciplinary forum on the progressing field of gerontology and geriatrics. The areas covered by the journal include: biogerontology, neurosciences, epidemiology, clinical gerontology and geriatric assessment, social, economical and behavioral gerontology. “Aging clinical and experimental research” appears bimonthly and publishes review articles, original papers and case reports.