The Genetic Jigsaw Puzzle Of Drug Addiction
Using an integrative meta-analysis approach, researchers from the Center for Bioinformatics at Peking University in Beijing have assembled the most comprehensive gene atlas underlying drug addiction and identified five molecular pathways common to four different addictive drugs.
Drug addiction is a serious worldwide problem with strong genetic and environmental influences. So far different technologies have revealed a variety of genes and biological processes underlying addiction. However, individual technology can be biased and render only an incomplete picture. Studying individual or a small number of genes is like looking at pieces of a jigsaw puzzle – only when you gather most of the pieces from different places and arrange them together in an orderly fashion do interesting patterns emerge.
The team, led by Liping Wei, surveyed scientific literature published in the past 30 years and collected 2,343 items of evidence linking genes and chromosome regions to addiction based on single-gene strategies, microarray, proteomics, or genetic studies.
They made this gene atlas freely available in the first online molecular database for addiction, named KARG (http://karg.cbi.pku.edu.cn), with extensive annotations and a user friendly interface.
Assembling the pieces of evidence together, the authors identified 18 molecular pathways that are statistically enriched in the addiction-related genes. They then identified five pathways that are common to addiction to four different substances. These common pathways may underlie shared rewarding and response mechanisms and may be targets for effective treatments for a wide range of addictive disorders.
PLoS Comput Biol 4(1): e2 doi:10.1371/journal.pcbi.0040002
Li CY, Mao X, Wei L (2008)
Genes and (Common) Pathways Underlying Drug Addiction.
Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn), the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways 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.