Genes and (Common) Pathways Underlying Drug AddictionPLoS Comput Biol 4(1): e2 January 4, 2008
Drug addiction has become one of the most serious problems in the world. It has been estimated that genetic factors contribute to 40%–60% of the vulnerability to drug addiction, and environmental factors provide the remainder.
What are the genes and pathways underlying addiction? Is there a common molecular network underlying addiction to different abusive substances? Is there any network property that may explain the long-lived and often irreversible molecular and structural changes after addiction? These important questions were traditionally studied experimentally. The explosion of genomic and proteomic data in recent years both enabled and necessitated bioinformatic studies of addiction.
We integrated data derived from multiple technology platforms and collected 2,343 items of evidence linking genes and chromosome regions to addiction. We identified 18 statistically significantly enriched molecular pathways. In particular, five of them were common for four types of addictive drugs (alcohol, cocaine, opioids, nicotine), which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction.
We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction.
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