TY - JOUR
T1 - Within subject cross-tissue analyzes of epigenetic clocks in substance use disorder postmortem brain and blood
AU - Cabrera-Mendoza, Brenda
AU - Stertz, Laura
AU - Najera, Katherine
AU - Selvaraj, Sudhakar
AU - Teixeira, Antonio L.
AU - Meyer, Thomas D.
AU - Fries, Gabriel R.
AU - Walss-Bass, Consuelo
N1 - Funding Information:
National Institute on Drug Abuse (NIDA) and the Fogarty Foundation National Institutes of Health (NIH), Grant/Award Number: R01DA044859; National Institute of Mental Health, Grant/Award Number: K01 MH121580 Funding information
Funding Information:
We are grateful for the invaluable donations and participation from families, as well as for the generous collaboration of the medical examiners at the Harris County Institute of Forensic Sciences.
Publisher Copyright:
© 2022 Wiley Periodicals LLC.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - 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.
AB - 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.
KW - DNA methylation
KW - cross-tissue
KW - epigenetic clocks
KW - opioid use disorder
KW - stimulants use disorder
KW - Brain
KW - Aging/genetics
KW - Epigenomics
KW - Humans
KW - Alcoholism
KW - DNA Methylation/genetics
KW - Substance-Related Disorders/genetics
KW - Epigenesis, Genetic/genetics
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U2 - 10.1002/ajmg.b.32920
DO - 10.1002/ajmg.b.32920
M3 - Article
C2 - 36056652
AN - SCOPUS:85137370168
SN - 1552-4841
VL - 192
SP - 13
EP - 27
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 1-2
ER -