Convergent functional genomics of cocaine misuse in humans and animal models

The American Journal of Drug and Alcohol Abuse
Diego A Forero, Yeimy González-Giraldo

Abstract

Background: Data from the Global Burden of Disease Study 2016 recently estimated that after opioid and cannabis use disorders, cocaine use disorders were among the most common, with around 5.8 million cases around the world. Several genome-wide expression studies (GWES) for cocaine misuse have been carried out in brain tissues from patients and controls and in mouse and rat models. Objectives: In the current work, we used a convergent functional genomics approach to identify novel candidate genes and pathways for cocaine misuse. Methods: We carried out meta-analyses for available GWES for cocaine misuse in humans and mouse and rat models (three, four, and two GWES, respectively). Multiple lines of evidence (GWES, genome-wide association and epigenomic data) were integrated to prioritize top candidate genes, and a functional enrichment analysis was carried out. Results: Several top candidate genes supported by multiple lines of genomic evidence, and with known roles in brain plasticity, were identified: APP, GRIN2A, GRIN2B, KCNA2, MAP4, PCDH10, PPP3CA, SNCB, and SV2C. An enrichment of genes regulated by the AP1 transcription factor was found. Conclusion: This is the first meta-analysis of GWES for cocaine misuse in humans and mo...Continue Reading

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Citations

May 27, 2020·Journal of Molecular Neuroscience : MN·Diego A Forero, Yeimy González-Giraldo
Feb 9, 2021·Neuroscience and Biobehavioral Reviews·Sandra Lopez-LeonDiego A Forero
Aug 29, 2021·Molecular Psychiatry·Noèlia Fernàndez-CastilloBru Cormand

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