Genome-wide Association Study of Smoking Initiation and Current Smoking

Department of Biological Psychology, Center for Neurogenomic and Cognitive Research, VU University Amsterdam, The Netherlands.
The American Journal of Human Genetics (Impact Factor: 10.93). 04/2009; 84(3):367-79. DOI: 10.1016/j.ajhg.2009.02.001
Source: PubMed


For the identification of genes associated with smoking initiation and current smoking, genome-wide association analyses were carried out in 3497 subjects. Significant genes that replicated in three independent samples (n = 405, 5810, and 1648) were visualized into a biologically meaningful network showing cellular location and direct interaction of their proteins. Several interesting groups of proteins stood out, including glutamate receptors (e.g., GRIN2B, GRIN2A, GRIK2, GRM8), proteins involved in tyrosine kinase receptor signaling (e.g., NTRK2, GRB14), transporters (e.g., SLC1A2, SLC9A9) and cell-adhesion molecules (e.g., CDH23). We conclude that a network-based genome-wide association approach can identify genes influencing smoking behavior.

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Available from: Henning Tiemeier
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    • "In the real data application, we identified two SNPs, rs6570989 and rs2930357, jointly associated with ND. In a recent GWAS of 3497 Dutch subjects, both of these two SNP were found to be significantly associated with current smoking [39]. These two SNPs are located in gene GRIK2 and CSMD1, respectively. "
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    • "Interestingly, electrophysiological studies linked variants within GRM8 to increased risk of vulnerability to alcoholism (Rangaswamy and Porjesz 2008; Chen et al. 2009). Furthermore, rs2237781 within GMR8 has been identified to be at risk for smoking initiation and suggests that members of the glutamate receptor family may associate with nicotine dependence and vulnerability to addiction (Vink et al. 2009). The neurotransmitter glutamate is involved in substance abuse behavior and may influence food intake (Stanley et al. 1993). "
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