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A genomewide association study of smoking relapse in four European population-based samples

Tozzi, Federicaa,b*; Teumer, Alexanderg*; Munafò, Marcusm*; Rawal, Rajeshe*; Kazeem, Gbengal; Gerbaulet, Marcelf; McArdle, Wendyn; Chilcoat, Howardc; Döring, Angelae; Dahmen, Norbertf; Mooser, Vincentd; Nauck, Matthiash; Ring, Susan Mn; Rubio, Justin P.l; Vollenweider, Petero; Waeber, Gérardo; John, Ulrichi; Völzke, Henryj; Homuth, Georgg; Freyberger, Harald J.k; Völker, Uweg; Davey-Smith, Georgen; Gieger, Christiane; Preisig, Martinp; Grabe, Hans J.k

doi: 10.1097/YPG.0b013e32835fc94b

Objectives 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.

Conclusion 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.

aGenetics Division, Quantitative Sciences, GlaxoSmithKline R&D, Verona, Italy

bDepartment of Psychiatry, School of Medicine, University of North Carolina, Chapel Hill

cWorldwide Epidemiology, Quantitative Sciences, GlaxoSmithKline, Research Triangle Park, North Carolina

dGenetics Division, GlaxoSmithKline R&D, Upper Merion, Pennsylvania, USA

eGerman Research Center for Environmental Health, Institute of Epidemiology and Helmholtz Zentrum München, Neuherberg

fDepartment of Psychiatry and Psychotherapy, University of Mainz, Mainz

gInterfaculty Institute for Genetics and Functional Genomics

hInstitute of Clinical Chemistry and Laboratory Medicine

iInstitute of Epidemiology and Social Medicine

jInstitute for Community Medicine, University of Greifswald, Greifswald

kDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS-Hospital Stralsund, Stralsund, Germany

lGenetics Division, Quantitative Sciences, GlaxoSmithKline R&D, Stevenage

mSchool of Experimental Psychology

nMRC CAiTE, School of Social and Community Medicine, University of Bristol, Bristol, UK

Departments of oInternal Medicine

pPsychiatry, University Hospital Center and University of Lausanne, Lausanne, Switzerland

*Federica Tozzi, Alexander Teumer, Marcus Munafò and Rajesh Rawal contributed equally to the writing of this article.

Correspondence to Hans J. Grabe, MD, Department of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS-Hospital Stralsund, Rostocker Chaussee 70, 18437 Stralsund, Germany Tel: +49 3831/45 2106; fax: +49 3831/45 2105; e-mail:

Received September 23, 2011

Received in revised form October 8, 2012

Accepted October 27, 2012

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