title: A genomewide association study of smoking relapse in four European population-based samples.
abstract: OBJECTIVE
  Genomewide association studies (GWAS) have identified clear evidence of genetic markers for nicotine dependence. Other smoking phenotypes have been tested, but the results are less consistent. The tendency to relapse versus the ability to maintain long-term abstinence has received little attention in genetic studies; thus, our aim was to provide a better biological understanding of this phenotype through the identification of genetic loci associated with smoking relapse.
  
  
  METHODS
  We carried out a GWAS on data from two European population-based collections, including a total of 835 cases (relapsers) and 990 controls (abstainers). Top-ranked findings from the discovery phase were tested for replication in two additional independent European population-based cohorts.
  
  
  RESULTS
  Of the seven top markers from the discovery phase, none were consistently associated with smoking relapse across all samples and none reached genomewide significance. A single-nucleotide polymorphism rs1008509, within the Xylosyltransferase II (XYLT2) gene, was suggestively associated with smoking relapse in the discovery phase (β=-0.504; P=5.6E-06) and in the first replication sample (ALSPAC) (β=-0.27; P=0.004; n=1932), but not in the second sample (KORA) (β=0.19; P=0.138; n=912). We failed to identify an association between loci implicated previously in other smoking phenotypes and smoking relapse.
  
  
  CONCLUSIONS
  Although no genomewide significant findings emerged from this study, we found that loci implicated in other smoking phenotypes were not associated with smoking relapse, which suggests that the neurobiology of smoking relapse and long-term abstinence may be distinct from biological mechanisms implicated in the development of nicotine dependence.
authors.affiliation: Genetics Division, Quantitative Sciences, GlaxoSmithKline R&D, Verona, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Tozzi
authors.forename: Alexander
authors.initials: A
authors.lastname: Teumer
authors.forename: Marcus
authors.initials: M
authors.lastname: Munafò
authors.forename: Rajesh
authors.initials: R
authors.lastname: Rawal
authors.forename: Gbenga
authors.initials: G
authors.lastname: Kazeem
authors.forename: Marcel
authors.initials: M
authors.lastname: Gerbaulet
authors.forename: Wendy
authors.initials: W
authors.lastname: McArdle
authors.forename: Howard
authors.initials: H
authors.lastname: Chilcoat
authors.forename: Angela
authors.initials: A
authors.lastname: Döring
authors.forename: Norbert
authors.initials: N
authors.lastname: Dahmen
authors.forename: Vincent
authors.initials: V
authors.lastname: Mooser
authors.forename: Matthias
authors.initials: M
authors.lastname: Nauck
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: Justin P
authors.initials: JP
authors.lastname: Rubio
authors.forename: Peter
authors.initials: P
authors.lastname: Vollenweider
authors.forename: Gérard
authors.initials: G
authors.lastname: Waeber
authors.forename: Ulrich
authors.initials: U
authors.lastname: John
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.forename: Harald J
authors.initials: HJ
authors.lastname: Freyberger
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.forename: George
authors.initials: G
authors.lastname: Davey-Smith
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Martin
authors.initials: M
authors.lastname: Preisig
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Grabe
mesh_terms: D016022:Case-Control Studies; D003710:Demography; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012008:Recurrence; D012907:Smoking / Q000235:genetics*; D044465:White People / Q000235:genetics*