title: Genomewide linkage survey of nicotine dependence phenotypes.
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.
  
  
  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.
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599-7264, USA. pfsulliv@med.unc.edu
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Sullivan
authors.forename: Po-Hsiu
authors.initials: PH
authors.lastname: Kuo
authors.forename: B Todd
authors.initials: BT
authors.lastname: Webb
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
authors.forename: Jen
authors.initials: J
authors.lastname: Vittum
authors.forename: Helena
authors.initials: H
authors.lastname: Furberg
authors.forename: Dermot
authors.initials: D
authors.lastname: Walsh
authors.forename: Diana G
authors.initials: DG
authors.lastname: Patterson
authors.forename: Brien
authors.initials: B
authors.lastname: Riley
authors.forename: Carol A
authors.initials: CA
authors.lastname: Prescott
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
mesh_terms: 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*