DOPA decarboxylase gene is associated with nicotine dependence.
BACKGROUND
Cigarette smoking is a prevalent and harmful behavior. Although the heritability of nicotine dependence (ND) is well documented and many candidate genetic regions have been identified, few of them were confirmed. This may be, in part, due to analytic methods that sacrifice power.


METHODS
Using a recently developed, more powerful method for testing association between a genetic marker and an ordinal trait, we analyzed data from 1879 smokers and nonsmokers from 600 nuclear families of African- or European-American (AA or EA) ancestry. This method increases power principally by accounting for differences in severity between affected subjects.


RESULTS
To demonstrate the more powerful method, we re-analyzed an existing dataset, which confirmed the association of the DOPA decarboxylase (DDC) gene on chromosome 7p11 with measures of nicotine dependence. Although none of the eight single nucleotide polymorphisms (SNPs) studied were found to be significantly associated with nicotine dependence (unadjusted p-value > 0.01), we identified haplotypes from those SNPs that were significantly associated with nicotine dependence in both AA and EA samples.


CONCLUSIONS
The associated haplotypes differed in the AA and EA samples. The strongest association (p-value = 0.003) was identified between the 'heaviness of smoking index' and haplotype C-A-T-G in SNPs rs921451-rs3735273-rs1451371-rs2060762. However, this association was not found significant in a previous report (p-value = 0.19) that used the same sample, underscoring the importance of using the statistical methods that use more of the available phenotypic information, and thereby better reflect the distribution of the phenotypes.
Zhang
Heping
H
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034, USA. Heping.Zhang@Yale.edu
Ye
Yuanqing
Y
Wang
Xueqing
X
Gelernter
Joel
J
Ma
Jennie Z
JZ
Li
Ming D
MD
D001741:Black or African American; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004296:Dopa Decarboxylase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide; D014029:Tobacco Use Disorder / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics; D044465:White People
D004296:Dopa Decarboxylase