Associations of variants in CHRNA5/A3/B4 gene cluster with smoking behaviors in a Korean population.
- Authors
- Li, Ming D; Yoon, Dankyu; Lee, Jong-Young; Han, Bok-Ghee; Niu, Tianhua; Payne, Thomas J; Ma, Jennie Z; Park, Taesung
- Year
- 2010
- Journal
- PloS one
- PMID
- 20808433
- DOI
- 10.1371/journal.pone.0012183
- PMCID
- PMC2922326
Multiple genome-wide and targeted association studies reveal a significant association of variants in the CHRNA5-CHRNA3-CHRNB4 (CHRNA5/A3/B4) gene cluster on chromosome 15 with nicotine dependence. The subjects examined in most of these studies had a European origin. However, considering the distinct linkage disequilibrium patterns in European and other ethnic populations, it would be of tremendous interest to determine whether such associations could be replicated in populations of other ethnicities, such as Asians. In this study, we performed comprehensive association and interaction analyses for 32 single-nucleotide polymorphisms (SNPs) in CHRNA5/A3/B4 with smoking initiation (SI), smoking quantity (SQ), and smoking cessation (SC) in a Korean sample (N = 8,842). We found nominally significant associations of 7 SNPs with at least one smoking-related phenotype in the total sample (SI: P = 0.015 approximately 0.023; SQ: P = 0.008 approximately 0.028; SC: P = 0.018 approximately 0.047) and the male sample (SI: P = 0.001 approximately 0.023; SQ: P = 0.001 approximately 0.046; SC: P = 0.01). A spectrum of haplotypes formed by three consecutive SNPs located between rs16969948 in CHRNA5 and rs6495316 in the intergenic region downstream from the 5' end of CHRNB4 was associated with these three smoking-related phenotypes in both the total and the male sample. Notably, associations of these variants and haplotypes with SC appear to be much weaker than those with SI and SQ. In addition, we performed an interaction analysis of SNPs within the cluster using the generalized multifactor dimensionality reduction method and found a significant interaction of SNPs rs7163730 in LOC123688, rs6495308 in CHRNA3, and rs7166158, rs8043123, and rs11072793 in the intergenic region downstream from the 5' end of CHRNB4 to be influencing SI in the male sample. Considering that fewer than 5% of the female participants were smokers, we did not perform any analysis on female subjects specifically. Together, our detected associations of variants in the CHRNA5/A3/B4 cluster with SI, SQ, and SC in the Korean smoker samples provide strong evidence for the contribution of this cluster to the etiology of SI, ND, and SC in this Asian population.
Haploview-generated LD patterns for 32 SNPs within the CHRNA5/A3/B4 cluster in the Korean total sample.Pair-wise LD between all SNPs was evaluated using the Haploview program [30] with the option of determining haplotype blocks according to the criteria defined by Gabriel et al. [31]. The number in each box represents the D' value for each SNP pair.
A summary of all reported SNPs that have been significantly associated with different smoking behaviors.Of these reported studies mentioned in the figure, most were investigated on nicotine dependence except that the study authored by Keskitalo et al. [55] was on serum cotinine level and that by Schlaepfer et al. [23] was on smoking initiation.
A summary of all reported haplotypes that have been significantly associated with different smoking behaviors in the AA, EA and Korean samples.
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|---|---|---|---|---|
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| <i>CHRNA5</i> rs16969968 and <i>CHRNA3</i> rs578776 polymorphisms are associated with multiple nicotine dependence phenotypes in Bangladeshi smokers. | Chaity NI et al. | — | 2022 | → |
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