title: Genetic linkage findings for DSM-IV nicotine withdrawal in two populations.
abstract: 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.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri 63110, USA. pergadim@psychiatry.wustl.edu
authors.forename: Michele L
authors.initials: ML
authors.lastname: Pergadia
authors.forename: Arpana
authors.initials: A
authors.lastname: Agrawal
authors.forename: Anu
authors.initials: A
authors.lastname: Loukola
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Ulla
authors.initials: U
authors.lastname: Broms
authors.forename: Scott F
authors.initials: SF
authors.lastname: Saccone
authors.forename: Jen C
authors.initials: JC
authors.lastname: Wang
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: Todorov
authors.forename: Kauko
authors.initials: K
authors.lastname: Heikkilä
authors.forename: Dixie J
authors.initials: DJ
authors.lastname: Statham
authors.forename: Anjali K
authors.initials: AK
authors.lastname: Henders
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Campbell
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
authors.forename: Richard D
authors.initials: RD
authors.lastname: Todd
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Heath
authors.forename: Alison M
authors.initials: AM
authors.lastname: Goate
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Pamela A F
authors.initials: PA
authors.lastname: Madden
mesh_terms: D002880:Chromosomes, Human, Pair 11; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D010641:Phenotype; D015995:Prevalence; D035781:Siblings; D012907:Smoking / Q000235:genetics; D013375:Substance Withdrawal Syndrome / Q000453:epidemiology / Q000235:genetics*; D013997:Time Factors; D014029:Tobacco Use Disorder / Q000453:epidemiology / Q000235:genetics*; D044465:White People / Q000235:genetics*