Within subject cross‐tissue analyzes of epigenetic clocks in substance use disorder postmortem brain and blood

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 192; no. 1-2; pp. 13 - 27
• Main Authors: Cabrera‐Mendoza, Brenda, Stertz, Laura, Najera, Katherine, Selvaraj, Sudhakar, Teixeira, Antonio L., Meyer, Thomas D., Fries, Gabriel R., Walss‐Bass, Consuelo
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.01.2023; Wiley Subscription Services, Inc
• Subjects: Aging; Aging - genetics; Alcoholism; Blood; Brain; cross‐tissue; DNA methylation; DNA Methylation - genetics; Drug addiction; Drug use; Epigenesis, Genetic - genetics; epigenetic clocks; Epigenetics; Epigenomics; Genetics; Humans; opioid use disorder; Prefrontal cortex; stimulants use disorder; Substance use; Substance use disorder; Substance-Related Disorders - genetics; opioid use disorder; DNA methylation; epigenetic clocks; cross-tissue; stimulants use disorder
• ISSN: 1552-4841; 1552-485X; 1552-485X
• DOI: 10.1002/ajmg.b.32920

There is a possible accelerated biological aging in patients with substance use disorders (SUD). The evaluation of epigenetic clocks, which are accurate estimators of biological aging based on DNA methylation changes, has been limited to blood tissue in patients with SUD. Consequently, the impact of biological aging in the brain of individuals with SUD remains unknown. In this study, we evaluated multiple epigenetic clocks (DNAmAge, DNAmAgeHannum, DNAmAgeSkinBlood, DNAmPhenoAge, DNAmGrimAge, and DNAmTL) in individuals with SUD (n = 42), including alcohol (n = 10), opioid (n = 19), and stimulant use disorder (n = 13), and controls (n = 10) in postmortem brain (prefrontal cortex) and blood tissue obtained from the same individuals. We found a higher DNAmPhenoAge (β = 0.191, p‐value = 0.0104) and a nominally lower DNAmTL (β = −0.149, p‐value = 0.0603) in blood from individuals with SUD compared to controls. SUD subgroup analysis showed a nominally lower brain DNAmTL in subjects with alcohol use disorder, compared to stimulant use disorder and controls (β = 0.0150, p‐value = 0.087). Cross‐tissue analyzes indicated a lower blood DNAmTL and a higher blood DNAmAge compared to their respective brain values in the SUD group. This study highlights the relevance of tissue specificity in biological aging studies and suggests that peripheral measures of epigenetic clocks in SUD may depend on the specific type of drug used.