Significant association of the CHRNB3-CHRNA6 gene cluster with nicotine dependence in the Chinese Han population

Abstract

Although numerous studies have revealed significant associations between variants in the nicotinic acetylcholine receptors (nAChR) subunits and nicotine dependence (ND), only few studies were performed in Chinese subjects. Here, we performed association and interaction analysis for 20 single nucleotide polymorphisms (SNPs) in the CHRNB3-CHRNA6 gene cluster with ND in a Chinese Han population (N = 5,055). We found nominally significant associations for all tested SNPs with ND measured by the Fagerström Test for Nicotine Dependence score; of these, 11 SNPs remained significant after Bonferroni correction for multiple tests (p = 9 × 10−4~2 × 10−3). Further conditional analysis indicated that no other SNP was significantly associated with ND independent of the most-highly significant SNP, rs6474414. Also, our haplotype-based association analysis indicated that each haplotype block was significantly associated with ND (p < 0.01). Further, we provide the first evidence of the genetic interaction of these two genes in affecting ND in this sample with an empirical p-value of 0.0015. Finally, our meta-analysis of samples with Asian and European origins for five SNPs in CHRNB3 showed significant associations with ND, with p-values ranging from 6.86 × 10−14 for rs13280604 to 6.50 × 10−8 for rs4950. This represents the first study showing that CHRNB3/A6 are highly associated with ND in a large Chinese Han sample.

Chronic obstructive pulmonary disease risk and smoking cessation changes induced by CHRNA5-A3 and CHRNB3-A6 variation in a Chinese male population

“…Nicotinic acetylcholine receptor (CHRN) genes code nAChRs, which bind to nicotinic that cause nicotinic dependence and smoking-related diseases. Recently, the associations of rs3743073 and rs667282 in CHRNA3-A5 and rs4950 in CHRNB3-A6 with tobacco consumption and lung cancer risk have been discovered [11,12,14,15]. Chronic smoking and environmental factors contribute to the development of lung cancer.…”

“…Smoking cessation is the only evidence-based intervention, which can reduce the risk of developing COPD and slow down the accelerated decline of lung function in patients with COPD [21]. Nicotine dependence and smoking cessation are influenced by genetic factors [14,15,22,23]. The study of Pérez-Rubio et al [24] demonstrated that rs6313 in HTR2A increased the risk for the early onset of smoking.…”

“…Although these phenotypes may share some genetic effects, it cannot be considered that the genetic association of nicotine dependence will translate into smoking cessation or vice versa [26]. Studies have shown that CHRNs are strongly associated with nicotine dependence [14,15,21,27]. Given the limited genetic contributions in nicotine dependence and smoking cessation, more research of the genetic study of smoking cessation is needed.…”

Association and cis-mQTL analysis of variants in serotonergic genes associated with nicotine dependence in Chinese Han smokers

“…The threshold for the genotyping rate of all SNPs was set as ≥95%, and the p value for the HWE was set as no ≥5%. All procedures and conditions used in this study were essentially the same as what we reported previously on the same samples 44 , 45 .…”

“…Association analysis with the FTND score was performed using Haplo Stats (v. 1.7.7) 50 . For the approach used for performing haplotype-based association analysis, please refer to our previous reports 43 , 44 .…”