RGD Reference Report - The CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster affects risk for nicotine dependence in African-Americans and in European-Americans. - Rat Genome Database

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The CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster affects risk for nicotine dependence in African-Americans and in European-Americans.

Authors: Saccone, Nancy L  Wang, Jen C  Breslau, Naomi  Johnson, Eric O  Hatsukami, Dorothy  Saccone, Scott F  Grucza, Richard A  Sun, Lingwei  Duan, Weimin  Budde, John  Culverhouse, Robert C  Fox, Louis  Hinrichs, Anthony L  Steinbach, Joseph Henry  Wu, Meng  Rice, John P  Goate, Alison M  Bierut, Laura J 
Citation: Saccone NL, etal., Cancer Res. 2009 Sep 1;69(17):6848-56. doi: 10.1158/0008-5472.CAN-09-0786. Epub 2009 Aug 25.
RGD ID: 150524362
Pubmed: PMID:19706762   (View Abstract at PubMed)
PMCID: PMC2874321   (View Article at PubMed Central)
DOI: DOI:10.1158/0008-5472.CAN-09-0786   (Journal Full-text)

Genetic association studies have shown the importance of variants in the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit gene cluster on chromosome 15q24-25.1 for the risk of nicotine dependence, smoking, and lung cancer in populations of European descent. We have carried out a detailed study of this region using dense genotyping in both European-Americans and African-Americans. We genotyped 75 known single nucleotide polymorphisms (SNPs) and one sequencing-discovered SNP in an African-American sample (N = 710) and in a European-American sample (N = 2,062). Cases were nicotine-dependent and controls were nondependent smokers. The nonsynonymous CHRNA5 SNP rs16969968 is the most significant SNP associated with nicotine dependence in the full sample of 2,772 subjects [P = 4.49 x 10(-8); odds ratio (OR), 1.42; 95% confidence interval (CI), 1.25-1.61] as well as in African-Americans only (P = 0.015; OR, 2.04; 1.15-3.62) and in European-Americans only (P = 4.14 x 10(-7); OR, 1.40; 1.23-1.59). Other SNPs that have been shown to affect the mRNA levels of CHRNA5 in European-Americans are associated with nicotine dependence in African-Americans but not in European-Americans. The CHRNA3 SNP rs578776, which has a low correlation with rs16969968, is associated with nicotine dependence in European-Americans but not in African-Americans. Less common SNPs (frequency



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CHRNA3Humannicotine dependence susceptibilityIAGP DNA:SNP: :rs578776(human)RGD 
CHRNA5Humannicotine dependence susceptibilityIAGP DNA:SNP: :rs16969968(human)RGD 
Chrna3Ratnicotine dependence susceptibilityISOCHRNA3 (Homo sapiens)DNA:SNP: :rs578776(human)RGD 
Chrna3Mousenicotine dependence susceptibilityISOCHRNA3 (Homo sapiens)DNA:SNP: :rs578776(human)RGD 
Chrna5Ratnicotine dependence susceptibilityISOCHRNA5 (Homo sapiens)DNA:SNP: :rs16969968(human)RGD 
Chrna5Mousenicotine dependence susceptibilityISOCHRNA5 (Homo sapiens)DNA:SNP: :rs16969968(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Chrna3  (cholinergic receptor nicotinic alpha 3 subunit)
Chrna5  (cholinergic receptor nicotinic alpha 5 subunit)

Genes (Mus musculus)
Chrna3  (cholinergic receptor, nicotinic, alpha polypeptide 3)
Chrna5  (cholinergic receptor, nicotinic, alpha polypeptide 5)

Genes (Homo sapiens)
CHRNA3  (cholinergic receptor nicotinic alpha 3 subunit)
CHRNA5  (cholinergic receptor nicotinic alpha 5 subunit)


Additional Information