Epigenome-wide association analyses of active injection drug use

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. 401 participants (Mage = 47.9; 68% male; 90% African Ameri...

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Bibliographic Details
Published in:Drug and alcohol dependence 2022-06, Vol.235, p.109431-109431, Article 109431
Main Authors: Shu, Chang, Jaffe, Andrew E., Sabunciyan, Sarven, Ji, Hongkai, Astemborski, Jacquie, Sun, Jing, Bakulski, Kelly M., Sosnowski, David W., Mehta, Shruti H., Kirk, Gregory D., Maher, Brion S.
Format: Article
Language:English
Subjects:
Abstinence
Adrenaline
African Americans
Biological effects
Blood
Buffy coat
Cell migration
Cocaine
Cohort Studies
CpG islands
CpG Islands - genetics
Deoxyribonucleic acid
DNA
DNA Methylation
Drug abuse
Drug use
Epigenesis, Genetic
Epigenetics
Epigenome
Epinephrine
Female
Genome-Wide Association Study
Health risks
Heroin
Humans
Inflammasomes
Injection
Injection drug use
Insulin
Lymphocytes
Lymphocytes T
Male
Microtubule-Associated Proteins - genetics
Middle Aged
Morbidity
Sociodemographics
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Summary: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. 401 participants (Mage = 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. 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 
ISSN:0376-8716
1879-0046
DOI:10.1016/j.drugalcdep.2022.109431