Epigenome-Wide Association Analyses of Active Injection Drug Use

Details

• Personal Author:
  Astemborski J ; Bakulski KM ; Jaffe AE ; Ji H ; Kirk GD ; Maher BS ; Mehta SH ; Sabunciyan S ; Shu C ; Sosnowski DW ; Sun J
• Description:
  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 (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. 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. [Description provided by NIOSH]
• Subjects:
  Cohort Studies Epidemiology Genetics Occupational Health Safety
• Keywords:
  Author Keywords: Injection Drug Use Cocaine Cohort Studies DNA Damage DNA Methylation Drug Use Epigenetics Heroin Longitudinal Study
• ISSN:
  0376-8716
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; Michigan ; New York ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  235
• NIOSHTIC Number:
  nn:20070620
• Citation:
  Drug Alcohol Depend 2022 Jun; 235:109431
• Contact Point Address:
  Brion S. Maher, Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, 624 N. Broadway, Rm 788, Hampton House, Baltimore, MI 21205, USA
• Email:
  brion@jhu.edu
• CAS Registry Number:
  Cocaine (CAS RN 50-36-2) ; Heroin (CAS RN 561-27-3)
• Federal Fiscal Year:
  2022
• Performing Organization:
  University of Michigan, Ann Arbor
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Drug and Alcohol Dependence
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8ae60019cc6aadc10bdccf54efcce3ed06c3cdc8e92458a69bb53648e5f5e4fb9cfeff5d7e75bd058dea6fe39fbd3aaebfa8c710d5f8b49e321f3077b4ee04e8
• Download URL:
  https://stacks.cdc.gov/view/cdc/208799/cdc_208799_DS1.pdf
• File Type:
  [PDF - 4.04 MB ]