Human Molecular Genetics Advance Access published online on June 1, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl144
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1 Department of Medicine (Genetics Program), Boston University Schools of Medicine and Public Health, Boston, MA
* To whom correspondence should be addressed. We report here a study considering association of alleles and haplotypes at the DOPA decarboxylase (DDC) locus with the DSM-IV diagnosis of nicotine dependence (ND) or a quantitative measure for ND using the Fagerstrom Test for Nicotine Dependence (FTND). We genotyped 18 single-nucleotide polymorphisms (SNPs) spanning a region of approximately 210 kb that includes DDC and the genes immediately flanking DDC in 1590 individuals from 621 families of African-American (AA) or European-American (EA) ancestry. Evidence of association (family-based tests) was observed with several SNPs for both traits (0.0002
Received March 23, 2006
Revised May 16, 2006
Accepted May 29, 2006
Article
Intronic Variants in the DOPA Decarboxylase (DDC) Gene are Associated with Smoking Behavior in European-Americans and African-Americans
Yi Yu 1,
Carolien Panhuysen 2,
Henry R. Kranzler 3,
Victor Hesselbrock 3,
Bruce Rounsaville 4,
Roger Weiss 5,
Kathleen Brady 6,
Lindsay A. Farrer 7,
and
Joel Gelernter 8 *
2 Department of Medicine (Genetics Program), Boston University Schools of Medicine and Public Health, Boston, MA; Department of Biostatistics, Boston University Schools of Medicine and Public Health, Boston, MA
3 Department of Psychiatry, University of Connecticut Health Center, Farmington, CT
4 Department of Psychiatry, Yale University School of Medicine; and VA CT Healthcare Center
5 Alcohol and Drug Abuse Treatment Program, McLean Hospital, Belmont, MA; Department of Psychiatry, Harvard Medical School, Boston, MA
6 Department of Psychiatry, Medical University of South Carolina, Charleston, SC
7 Department of Medicine (Genetics Program), Boston University Schools of Medicine and Public Health, Boston, MA; Department of Biostatistics, Boston University Schools of Medicine and Public Health, Boston, MA; Department of Neurology, Genetics & Genomics, and Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA
8 Department of Neurobiology, Yale University School of Medicine; Yale University School of Medicine, Department of Psychiatry, Division of Human Genetics in Psychiatry; VA CT 116A2; 950 Campbell Avenue; West Haven, CT 06516
Joel Gelernter, E-mail: joel.gelernter{at}yale.edu
Abstract 
p0.04). The most significant result was obtained for the relationship of FTND score to SNP rs12718541 (AA families: p = 0.002; EA families: p = 0.03; all families: p = 0.0002) which is in the same intron as the splice site for a neuronal isoform of human DDC lacking exons 10-15. Haplotype analysis did not reveal any SNP combination with stronger evidence for association than rs12718541 alone. Although sequence analysis suggests that rs12718541 may be an intronic splicing enhancer, further studies are needed to determine whether a direct link exists between an alternatively spliced form of DDC and predisposition to ND. These findings confirm a previous report of association of DDC with ND, localize the causative variants to the 3'end of the coding region, and extend the association to multiple population groups.
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