Multiple cholinergic nicotinic receptor genes affect nicotine dependence risk in African and European Americans.
paper
Cited
Public
- Authors
- Saccone, N L; Schwantes-An, T-H; Wang, J C; Grucza, R A; Breslau, N; Hatsukami, D; Johnson, E O; Rice, J P; Goate, A M; Bierut, L J
- Year
- 2010
- Journal
- Genes, brain, and behavior
- PMID
- 20584212
- DOI
- 10.1111/j.1601-183X.2010.00608.x
- PMCID
- PMC2970751
Several independent studies show that the chromosome 15q25.1 region, which contains the CHRNA5-CHRNA3-CHRNB4 gene cluster, harbors variants strongly associated with nicotine dependence, other smoking behaviors, lung cancer and chronic obstructive pulmonary disease. We investigated whether variants in other cholinergic nicotinic receptor subunit (CHRN) genes affect the risk of nicotine dependence in a new sample of African Americans (AAs) (N = 710). We also analyzed this AA sample together with a European American (EA) sample (N = 2062, 1608 of which have been previously studied), allowing for differing effects in the two populations. Cases are current nicotine-dependent smokers and controls are non-dependent smokers. Variants in or near CHRND-CHRNG, CHRNA7 and CHRNA10 show modest association with nicotine dependence risk in the AA sample. In addition, CHRNA4, CHRNB3-CHRNA6 and CHRNB1 show association in at least one population. CHRNG and CHRNA4 harbor single nucleotide polymorphisms (SNPs) that have opposite directions of effect in the two populations. In each of the population samples, these loci substantially increase the trait variation explained, although no loci meet Bonferroni-corrected significance in the AA sample alone. The trait variation explained by three key associated SNPs in CHRNA5-CHRNA3-CHRNB4 is 1.9% in EAs and also 1.9% in AAs; this increases to 4.5% in EAs and 7.3% in AAs when we add six variants representing associations at other CHRN genes. Multiple nicotinic receptor subunit genes outside chromosome 15q25 are likely to be important in the biological processes and development of nicotine dependence, and some of these risks may be shared across diverse populations.
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| Name | Type |
|---|---|
| AA | cohort |
| AA-only sample local | cohort |
| AA sample | cohort |
| African American | cohort |
| African-Americans | cohort |
| African-ancestry samples local | cohort |
| age | phenotype |
| Asian | cohort |
| Australian population | cohort |
| Australian subjects local | cohort |
| brain | anatomy |
| case/control status | phenotype |
| CEU | cohort |
| CHRNA10 | gene |
| Chrna3 | gene |
| Chrna4 | gene |
| CHRNA5 | gene |
| CHRNA5-CHRNA3-CHRNB4 cluster | gene |
| Chrna6 | gene |
| Chrna7 | gene |
| Chrnb1 | gene |
| Chrnb3 | gene |
| CHRNB3-CHRNA6 local | gene |
| Chrnb4 | gene |
| CHRND | gene |
| CHRNG | gene |
| CHRN genes local | gene |
| chronic obstructive pulmonary disease | phenotype |
| Cigarettes-per-day local | phenotype |
| COGEND | cohort |
| Combined European American sample local | cohort |
| combined sample | cohort |
| dbSNP build 129 local | drug |
| dizziness in response to tobacco local | phenotype |
| EA | cohort |
| EAs | cohort |
| EIGENSTRAT analysis local | drug |
| European-American COGEND subjects local | cohort |
| European ancestry | cohort |
| European-ancestry US/Australia cohort local | cohort |
| European-descent Australians local | cohort |
| European population | cohort |
| Europeans | cohort |
| expanded United States sample local | cohort |
| FTND | phenotype |
| full sample | cohort |
| gender local | drug |
| HapMap3 | cohort |
| HapMap CEU | cohort |
| HapMap HCB-JPT local | cohort |
| Illumina Golden Gate local | drug |
| lung cancer | phenotype |
| NCBI Human Reference Build 36.2 local | drug |
| New European American sample local | cohort |
| nicotine | drug |
| nicotine dependence | phenotype |
| nicotinic acetylcholine receptor | drug |
| Original European American sample local | cohort |
| phenotypic variation | phenotype |
| population | cohort |
| principal components | drug |
| rs10438287 local | variant |
| rs10958726 local | variant |
| rs12915265 local | variant |
| rs13277254 local | variant |
| rs13277524 | variant |
| rs16925377 local | variant |
| rs16969968 | variant |
| rs1881492 local | variant |
| rs1909884 local | variant |
| rs1955186 local | variant |
| rs2229959 local | variant |
| rs2231532 local | variant |
| rs2236196 | variant |
| rs2302761 local | variant |
| rs2302763 local | variant |
| rs3855924 local | variant |
| rs4779565 local | variant |
| rs4796418 local | variant |
| rs4952 local | variant |
| rs578776 | variant |
| rs588765 | variant |
| rs6494212 | variant |
| rs7210231 local | variant |
| rs904951 local | variant |
| rs904952 local | variant |
| Sequenom iPlex local | drug |
| sex | phenotype |
| smoking | phenotype |
| smoking behavior | phenotype |
| smoking cessation | phenotype |
| smoking prevalence | phenotype |
| smoking quantity | phenotype |
| Smoking risk local | phenotype |
| SNP | cohort |
| SNP_CHRNA10 local | variant |
| SNP_CHRNA7 local | variant |
| SNP_CHRNG local | variant |
| SNPs (Table 3) local | variant |
| SNP term local | variant |
| United States | cohort |
| YRI | cohort |
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