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Study Explores Genetic Overlap Between Nicotine Addiction, Schizophrenia

NEW YORK (GenomeWeb) – A dozen genetic pathways may contribute to both schizophrenia risk and nicotine addiction susceptibility, new research suggests.

Researchers from Tianjin Medical University and the University of South Florida (USF) set out to explore genetic contributors to both traits based on prior epidemiological studies that described particularly high rates of tobacco use in individuals with schizophrenia. Using pathway and network analyses on genes implicated in schizophrenia and nicotine addiction in the past, they narrowed in on dozens of shared risk genes, which were over-represented in 12 pathways involved in everything from signaling to synaptic function.

When the team put together genetic sub-networks associated with nicotine addiction and schizophrenia risk, meanwhile, it teased out apparent cross-trait associations for 11 genes that were not linked to smoking or schizophrenia in the past. The study, published online today in Scientific Reports, also included a schematic molecular network that provided an overview of the smoking-schizophrenia relationships teased out of such analyses.

"Our results may provide an alternative view on exploring the linkage between nicotine addiction and schizophrenia, and suggest that a system-level approach used in this work can be promising for understanding the pathogenetic association between diseases," co-corresponding authors Ju Wang, a biomedical engineering researcher at Tianjin Medical University, and Feng Cheng, a pharmaceutical science researcher at USF, and their co-authors wrote.

The use of tobacco and other substances appears to be significantly higher in individuals with schizophrenia compared with unaffected individuals, the team noted. And while environmental contributors or incidences of self-medication might contribute to such patterns, the widespread tobacco use in schizophrenia is believed to have a genetic basis as well.

To explore that possibility, the researchers did a series of pathway enrichment and network analyses focusing on the 276 genes and the 331 genes previously linked to nicotine addiction and schizophrenia risk, respectively, in published papers and public databases. The collections included 52 overlapping genes, they reported, including representatives from dopaminergic, serotonergic, glutamatergic, and nicotinic neurotransmitter pathways and pathways involved in cellular transport, drug metabolism, or drug addiction.

Still more overlapping biological processes turned up when the team did gene ontology-informed functional enrichment and pathway enrichment analyses. While eight pathways appeared to be specific to nicotine addiction, and 11 pathways were reportedly schizophrenia-specific, for example, 12 pathways appeared to be shared between the conditions.

Based on information gleaned from protein-protein interaction networks and condition-specific sub-networks, meanwhile, the researchers identified 11 genes that each interacted with at least five of the overlapping smoking and schizophrenia genes. 

"Most of these genes have been reported to be associated with nicotine addiction, schizophrenia, or both diseases through various experimental approaches," the authors wrote, noting that "involvement of these new susceptible genes pathways associated with both nicotine addiction and schizophrenia provides further evidence for their connection with the two diseases."