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Drug Alcohol Depend. 2008 Mar 1;93(3):210-6. Epub 2007 Nov 19.

Genomewide linkage survey of nicotine dependence phenotypes.

Author information

1
Department of Genetics, University of North Carolina, Chapel Hill, NC 27599-7264, USA. pfsulliv@med.unc.edu

Abstract

BACKGROUND:

A comprehensive understanding of the etiology and neurobiology of nicotine dependence is not available. We sought to identify genomic regions that might contain etiologically-relevant loci using genomewide univariate and bivariate linkage analyses.

METHODS:

We conducted secondary data analyses of 626 all possible sibling pairs ascertained in Ireland and Northern Ireland on the basis of alcohol dependence. A set of 1020 short tandem repeat genetic markers were genotyped in all subjects. The phenotypes analyzed were the Fagerström Test for Nicotine Dependence (FTND), a history of nicotine dependence, the number of symptoms of alcohol dependence (AlcSx), and a history of alcohol dependence. Genomewide linkage analyses were conducted with non-parametric and variance components methods.

FINDINGS:

For the bivariate variance component analysis of the continuous FTND and AlcSx scores, multipoint LOD scores were >4 in two genomic regions--an 11cM region on chr7 (D7S2252-D7S691, empirical p=0.0006) and an 8cM region on chr18 flanking D18S63 (empirical p=0.0007). These findings did not exceed a conservative estimate of study-wide significance. The remaining sets of findings had considerably smaller or less consistent peak signals. Notably, strong linkage signal at D4S1611 for AlcSx from a prior report (PMID 16534506) was not found when jointly analyzed with FTND.

INTERPRETATION:

Replication is required. However, chromosomes 7 and 18 may contain genetic loci relevant to the etiology of nicotine-related phenotypes.

PMID:
18023296
PMCID:
PMC2258277
DOI:
10.1016/j.drugalcdep.2007.09.015
[Indexed for MEDLINE]
Free PMC Article

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