Linked Life Data

17164261

Source:http://linkedlifedata.com/resource/pubmed/id/17164261

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-1-26
pubmed:abstractText
A two-stage association study was conducted targeting a genomic region on chromosome 17p13 that we reported likely to harbor susceptibility gene(s) for nicotine dependence (ND). Participants were 2037 subjects from 602 nuclear families of either African-American (AA) or European-American (EA) origin from our Mid-South Tobacco Family (MSTF) cohort. We first examined 10 single nucleotide polymorphisms (SNPs) in six genes within the targeted region of about 90 kb to determine which SNP/gene was associated with ND, assessed by smoking quantity (SQ), the heaviness of smoking index (HSI) and the Fagerström Test for ND (FTND). Individual SNP analysis revealed that SNPs rs17710 and rs222843 in GABA(A) receptor-associated protein (GABARAP) exhibited a significant association with at least one age- and gender-adjusted ND measure in the EA sample and rs222843 remained significant with the FTND after correction for multiple testing (P = 0.009). Although no SNP in DLG4 was significantly associated with ND, we found a G-G haplotype with a frequency of 14.2% formed by SNPs rs2242449 and rs507506 within the gene that showed significant inverse associations with all three ND measures [P = 0.003, 0.015 and 0.024, for SQ (defined as the number of cigarettes smoked per day), HSI and FTND, respectively]. We also found an A-A haplotype with a frequency of 8.8% formed by SNPs rs17710 and rs222843 in GABARAP, which revealed significant associations with all three ND measures (P = 0.006, 0.019 and 0.024, for SQ, HSI and FTND, respectively). To confirm these findings with a better coverage of GABARAP and DLG4, we conducted a second-stage association analysis by genotyping four more SNPs for GABARAP and nine more for DLG4 on the same set of samples. Our results from the second stage of individual SNP- and/or haplotype-based association analysis supported our finding of significant association of the DLG4 gene with ND. No significant association of GABARAP or DLG4 with ND was detected in the AA sample. Further, by comparing the linkage signal before and after adjustment for the SNPs of GABARAP and DLG4, we found that inclusion of the SNPs of the two genes as covariates largely reduced the linkage signal in the EA sample, but kept nearly unchanged in the AA sample. Taken together, our two-stage association analysis and linkage analysis results indicate that the GABARAP and DLG4 genes are involved in the etiology of ND in EA smokers. Further investigation of neurobiological mechanisms of the two genes in the etiology of ND is thus warranted.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
142-53
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17164261-Adaptor Proteins, Signal Transducing, pubmed-meshheading:17164261-Chromosome Mapping, pubmed-meshheading:17164261-Chromosomes, Human, Pair 17, pubmed-meshheading:17164261-DNA Primers, pubmed-meshheading:17164261-European Continental Ancestry Group, pubmed-meshheading:17164261-Genetic Predisposition to Disease, pubmed-meshheading:17164261-Genotype, pubmed-meshheading:17164261-Haplotypes, pubmed-meshheading:17164261-Humans, pubmed-meshheading:17164261-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:17164261-Linkage Disequilibrium, pubmed-meshheading:17164261-Membrane Proteins, pubmed-meshheading:17164261-Microtubule-Associated Proteins, pubmed-meshheading:17164261-Polymorphism, Single Nucleotide, pubmed-meshheading:17164261-Smoking, pubmed-meshheading:17164261-Tobacco Use Disorder, pubmed-meshheading:17164261-United States
pubmed:year
2007
pubmed:articleTitle
Fine mapping of a linkage region on chromosome 17p13 reveals that GABARAP and DLG4 are associated with vulnerability to nicotine dependence in European-Americans.
pubmed:affiliation
Department of Psychiatry and Neurobehavioral Sciencesm, University of Virginia, Charlottesville, VA, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural