Convergence of genetic findings for nicotine dependence and smoking related diseases with chromosome 15q24-25

Abstract

Due to the adverse health consequences related to smoking, it is important to understand factors that contribute to nicotine dependence. The most replicated genetic finding for nicotine dependence points to variants on chromosome 15, which includes the alpha5-alpha3-beta4 nicotinic receptor gene cluster. A compelling functional variant is a polymorphism, rs16969968, which alters an amino acid in the alpha5 nicotinic receptor subunit. Several prominent studies report that the replicated nicotine dependence locus also influences the risk for lung cancer and chronic obstructive pulmonary disease. This represents an exciting convergence of genetic findings, and highlights the potential for research on smoking to inform public health.

Figure 1

Per Capita cigarette consumption and lung cancer death rate in the U.S. from 1900–2005. Lung cancer prevalence over the 20^th century reflects changes in cigarette consumption.

Figure 2

SNPs correlated with rs16969968 on chromosome 15. The SNP rs16969968 is marked by the largest diamond. This SNP is highly correlated (r² > 0.8) with SNPs that span approximately 120 kilobases across multiple genes including the α5-α3-β4 nicotinic receptor gene cluster. Figure generated by SNAP [42].