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470 Associations with gene-transcript expressions in cocaine use disorder reveal genetic predispositions with other substance use and cardio-neurovascular disease.

Published online by Cambridge University Press:  03 April 2024

Chinwe Nwaneshiudu
Affiliation:
Icahn School of Medicine at Mount Sinai Hospital
Kiran Girdhar
Affiliation:
Icahn School of Medicine at Mount Sinai Hospital Center for Disease Neurogenomics, Friedman Brain Institute,Icahn Institute for Data Science and Genomic Technology Department of Psychiatry, Department of Genetics and Genomic Science
Rita Z. Goldstein
Affiliation:
Department of Psychiatry, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, USA
Eduardo Butelman
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA
Nelly Alia-Klein
Affiliation:
Department of Psychiatry, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, USA
Panos Roussos
Affiliation:
Center for Disease Neurogenomics, Friedman Brain Institute,Icahn Institute for Data Science and Genomic Technology Department of Psychiatry, Department of Genetics and Genomic Science Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, USA, Mental Illness Research Education and Clinical Center (MIRECC)
James J. Peters
Affiliation:
VA Medical Center, Bronx, New York, USA, Hess Center for Science and Medicine, New York
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Abstract

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OBJECTIVES/GOALS: Using biomarkers to identify vulnerabilities from cocaine use disorder (CUD) is a focus of recent investigations. Current clinical efforts focus on psychiatric recovery in CUD, however other body systems are missed. Applying blood-based transcriptomics to investigate how clinical conditions relate to CUD can alter current treatment approaches. METHODS/STUDY POPULATION: We conducted a comprehensive longitudinal study of 12 individuals (mean 53 yrs.; M/F ratio 9: 3) with CUD abstinent from cocaine. 44 blood samples collected repeatedly every 3 months for 9 months were bulk RNA sequenced. We began with phenotype harmonization grouping individuals with the following metrics; cocaine withdrawal, cue craving, generalized craving, perceived stress, and days of abstinence. We ran differential gene and transcript expression with time across grouping of metrics using the dream software and used the multivariate test to examine their associations. We used the association of gene-transcripts to determine genetic predispositions with clinical traits using the Multi-marker Analysis of GenoMic Annotation assessing their overlap to a reference GWAS database. RESULTS/ANTICIPATED RESULTS: Individuals were grouped in 2 clusters based on scores of cue craving, generalized craving, cocaine withdrawal, and 3 clusters based on days of abstinence from cocaine use. Gene-transcript(s) associationsrevealed genetic predisposition towards certain clinical conditions and substance use traits. Cannabis use disorder showed significant enrichment between the greater vs. lesser abstinent days, and lesser vs. least abstinent days at 9 months. The “drinks per week” trait showed significant gene enrichment between greater vs. lesser abstinent days at 9 months. Coronary artery disease was also enriched with greater vs. least abstinent days at 3 months. Lastly, significant baseline differences in predisposition to small vessel ischemic stroke were seen in responders with high vs low perceived stress. DISCUSSION/SIGNIFICANCE: These results from a robust and feasible pipeline suggest genetic predisposition in CUD for other substances and cardio-neurovascular diseases. This pilot study may lead to larger studies into whole genome-based blood biomarker approaches for monitoring abstinence and other clinical co-morbidities to be addressed in cocaine addiction recovery.

Type
Precision Medicine/Health
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NCCreative Common License - ND
This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.
Copyright
© The Author(s), 2024. The Association for Clinical and Translational Science