CHRNA3 and nicotine dependence: In addition, genetic variation in the nicotinic acetylcholine receptor (nAChR) gene cluster CHRNA5-CHRNA3-CHRNB4 has been shown to be significantly associated with nicotine dependence [13,14], smoking quantity [15,16,17,18,19,20,21] and smoking-related diseases such as chronic obstructive pulmonary disease [21], peripheral arterial disease [22] and lung cancer [22,23,24,25,26].