Epigenome-wide association analyses of active injection drug use

Chang Shu; Andrew E Jaffe; Sarven Sabunciyan; Hongkai Ji; Jacquie Astemborski; Jing Sun; Kelly M Bakulski; David W Sosnowski; Shruti H Mehta; Gregory D Kirk; Brion S Maher

doi:10.1016/j.drugalcdep.2022.109431

Epigenome-wide association analyses of active injection drug use

Drug Alcohol Depend. 2022 Jun 1:235:109431. doi: 10.1016/j.drugalcdep.2022.109431. Epub 2022 Mar 29.

Authors

Affiliations

¹ Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.
² Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
³ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁵ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁶ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
⁷ Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁸ Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: brion@jhu.edu.

PMID: 35395503
DOI: 10.1016/j.drugalcdep.2022.109431

Abstract

Background: Injection drug use (IDU) is prevalent in the US and is associated with substantial risk of blood-borne infections, morbidity, and mortality. However, the spectrum of its biologic effects on DNA methylation in blood is not well characterized.

Methods: 401 participants (M_age = 47.9; 68% male; 90% African American) over several timepoints (1054 visits) were drawn from a longitudinal cohort of people who inject drugs. DNA methylation was measured among buffy coat samples from the 1054 visits. Compared to samples collected after ≥ 6 months of abstinence, separate EWAS were conducted for active injecting of any drug, quantitative injection frequency, injecting of heroin and injecting of cocaine. Linear mixed effect models were used and analyses were adjusted for repeated measurements and key technical, biological, and sociodemographic characteristics.

Results: We found epigenome-wide significant CpG sites associated with active injection (cg10636246, AIM2, p = 2.33 × 10^-8) and injection intensity (cg13117953, p = 4.30 × 10^-8). We found converging evidence that cg10636246 (AIM2), cg23110600 (PRKCH), cg03546163 (FKBP5), cg04590956 (GMCL1), and cg16317961 (MAPRE2) were among the top 0.1% significantly differentially methylated CpG sites shared across the five EWAS. Top ranked CpGs among the five EWAS were enriched (p < 0.0001) in AIM2 inflammasome complex, T cell migration, insulin regulation and epinephrine synthesis pathways. During periods of active injection, samples had 0.46 years of epigenetic age acceleration relative to the abstinence period, within the same subject (p = 0.03).

Conclusions: Findings from this study demonstrate modest, common, and specific effects on DNA methylation during a relatively short time between periods of active drug injection and abstinence.

Keywords: Cocaine; DNA methylation; Epigenetics; Heroin; Injection drug use.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Cohort Studies
CpG Islands / genetics
DNA Methylation
Epigenesis, Genetic
Epigenome*
Female
Genome-Wide Association Study*
Humans
Male
Middle Aged
Substance-Related Disorders* / diagnosis
Substance-Related Disorders* / genetics

Abstract

Publication types

MeSH terms

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