Genetic linkage findings for DSM-IV nicotine withdrawal in two populations

Michele L. Pergadia, Arpana Agrawal, Anu Loukola, Grant W. Montgomery, Ulla Broms, Scott F. Saccone, Jen C. Wang, Alexandre A. Todorov, Kauko Heikkilä, Dixie J. Statham, Anjali K. Henders, Megan J. Campbell, John P. Rice, Richard D. Todd, Andrew C. Heath, Alison M. Goate, Leena Peltonen, Jaakko Kaprio, Nicholas G. Martin, Pamela A.F. Madden

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Nicotine withdrawal (NW) is both an important contributor to difficulty quitting cigarettes and because of mood-related withdrawal symptoms a problem of particular relevance to psychiatry. Twin-studies suggest that genetic factors influence NW (heritability=45%). Only one previous linkage study has published findings on NW [Swan et al. (2006); Am J Med Genet Part B 141B:354-360; LOD=2.7; Chr. 6 at 159 cM]. As part of an international consortium, genome-wide scans (using over 360 autosomal microsatellite markers) and telephone diagnostic interviews were conducted on 289 Australian (AUS) and 161 Finnish (FIN, combined (COMB) N=450 families) families ascertained from twin registries through index-cases with a lifetime history of cigarette smoking. The statistical approach used an affected-sib-pair design (at least two adult full siblings reported a history of DSM-IV NW) and conducted the linkage analyses using MERLIN. Linkage signals with LOD scores >1.5 were found on two chromosomes: 6 (FIN: LOD=1.93 at 75 cM) and 11 at two different locations (FIN: LOD=3.55 at 17 cM, and AUS: LOD=1.68 with a COMB: LOD=2.30 at 123 cM). The multipoint LOD score of 3.55 on chromosome 11p15 in FIN met genomewide significance (P=0.013 with 1,000 simulations). At least four strong candidate genes lie within or near this peak on chromosome 11: DRD4, TPH, TH, and CHRNA10. Other studies have reported that chromosome 11 may harbor genes associated with various aspects of smoking behavior. This study adds to that literature by highlighting evidence for NW.

Original languageEnglish
Pages (from-to)950-959
Number of pages10
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number7
StatePublished - Oct 5 2009


  • Genetics
  • Linkage
  • Nicotine
  • Withdrawal


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