Genetic linkage findings for DSM-IV nicotine withdrawal in two populations.
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.
Pergadia
Michele L
ML
Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri 63110, USA. pergadim@psychiatry.wustl.edu
Agrawal
Arpana
A
Loukola
Anu
A
Montgomery
Grant W
GW
Broms
Ulla
U
Saccone
Scott F
SF
Wang
Jen C
JC
Todorov
Alexandre A
AA
Heikkilä
Kauko
K
Statham
Dixie J
DJ
Henders
Anjali K
AK
Campbell
Megan J
MJ
Rice
John P
JP
Todd
Richard D
RD
Heath
Andrew C
AC
Goate
Alison M
AM
Peltonen
Leena
L
Kaprio
Jaakko
J
Martin
Nicholas G
NG
Madden
Pamela A F
PA
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*