Genomewide linkage survey of nicotine dependence phenotypes.
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.


RESULTS
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.


CONCLUSIONS
Replication is required. However, chromosomes 7 and 18 may contain genetic loci relevant to the etiology of nicotine-related phenotypes.
Sullivan
Patrick F
PF
Department of Genetics, University of North Carolina, Chapel Hill, NC 27599-7264, USA. pfsulliv@med.unc.edu
Kuo
Po-Hsiu
PH
Webb
B Todd
BT
Neale
Michael C
MC
Vittum
Jen
J
Furberg
Helena
H
Walsh
Dermot
D
Patterson
Diana G
DG
Riley
Brien
B
Prescott
Carol A
CA
Kendler
Kenneth S
KS
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000150:complications / Q000453:epidemiology; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D003625:Data Collection; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009660:Northern Ireland / Q000453:epidemiology; D010641:Phenotype; D020080:Tandem Repeat Sequences; D014029:Tobacco Use Disorder / Q000150:complications / Q000235:genetics* / Q000523:psychology*