A Direct Comparison of the Relationship of Epigenetic Aging and Epigenetic Substance Consumption Markers to Mortality in the Framingham Heart Study

James A Mills; Steven R H Beach; Meeshanthini Dogan; Ron L Simons; Frederick X Gibbons; Jeffrey D Long; Robert Philibert

doi:10.3390/genes10010051

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A Direct Comparison of the Relationship of Epigenetic Aging and Epigenetic Substance Consumption Markers to Mortality in the Framingham Heart Study

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A Direct Comparison of the Relationship of Epigenetic Aging and Epigenetic Substance Consumption Markers to Mortality in the Framingham Heart Study

James A Mills, Steven R H Beach, Meeshanthini Dogan, Ron L Simons, Frederick X Gibbons, Jeffrey D Long and Robert Philibert

Genes, Vol.10(1), p.51

01/15/2019

DOI: 10.3390/genes10010051

PMCID: PMC6356614

PMID: 30650672

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Abstract

A number of studies have examined the relationship of indices of epigenetic aging (EA) to key health outcomes. Unfortunately, our understanding of the relationship of EA to mortality and substance use-related health variables is unclear. In order to clarify these interpretations, we analyzed the relationship of the Levine EA index (LEA), as well as established epigenetic indices of cigarette (cg05575921) and alcohol consumption (cg04987734), to all-cause mortality in the Framingham Heart Study Offspring Cohort ( = 2256) Cox proportional hazards regression. We found that cg05575921 and cg04987734 had an independent effect relative to LEA and vice versa, with the model including all the predictors having better performance than models with either LEA or cg05575921 and cg04987734 alone. After correction for multiple comparisons, 195 and 327, respectively, of the 513 markers in the LEA index, as well as the overall index itself, were significantly associated with cg05575921 and cg04987734 methylation status. We conclude that the epigenetic indices of substance use have an independent effect over and above LEA, and are slightly stronger predictors of mortality in head-to-head comparisons. We also conclude that the majority of the strength of association conveyed by the LEA is secondary to smoking and drinking behaviors, and that efforts to promote healthy aging should continue to focus on addressing substance use.

Epigenesis, Genetic

Humans

Middle Aged

Male

Cardiovascular Diseases - genetics

DNA Methylation

Aging - genetics

Alcohol Drinking - epidemiology

Smoking - epidemiology

Cardiovascular Diseases - epidemiology

Cardiovascular Diseases - mortality

Female

Aged

Details

Title: Subtitle: A Direct Comparison of the Relationship of Epigenetic Aging and Epigenetic Substance Consumption Markers to Mortality in the Framingham Heart Study
Creators: James A Mills - Department of Psychiatry, University of Iowa, Iowa City, IA 52242, USA. Jim-mills@uiowa.edu
Steven R H Beach - Center for Family Research, University of Georgia, Athens, GA 30602, USA. srhbeach@uga.edu
Meeshanthini Dogan - Cardio Diagnostics LLC, Coralville, IA 52241, USA. mdogan@bdmethylation.com
Ron L Simons - Center for Family Research, University of Georgia, Athens, GA 30602, USA. ron.lee.simons@gmail.com
Frederick X Gibbons - Department of Psychology, University of Connecticut, Stoors, CT 06268, USA. rick.gibbons@uconn.edu
Jeffrey D Long - Department of Biostatistics, University of Iowa, Iowa City, IA 52242, USA. Jeffrey-long@uiowa.edu
Robert Philibert - Behavioral Diagnostics LLC, Coralville, IA 52241, USA. robert-philibert@uiowa.edu
Resource Type: Journal article
Publication Details: Genes, Vol.10(1), p.51
DOI: 10.3390/genes10010051
PMID: 30650672
PMCID: PMC6356614
NLM abbreviation: Genes (Basel)
ISSN: 2073-4425
eISSN: 2073-4425
Publisher: Switzerland
Grant note: R01 DA037648 / NIDA NIH HHS R44 CA213507 / NCI NIH HHS R44 AA022041 / NIAAA NIH HHS
Language: English
Date published: 01/15/2019
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Psychiatry; Iowa Neuroscience Institute; Biostatistics
Record Identifier: 9984003965002771

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