Premium
Genetic linkage findings for DSM‐IV nicotine withdrawal in two populations
Author(s) -
Pergadia Michele L.,
Agrawal Arpana,
Loukola Anu,
Montgomery Grant W.,
Broms Ulla,
Saccone Scott F.,
Wang Jen C.,
Todorov Alexandre A.,
Heikkilä Kauko,
Statham Dixie J.,
Henders Anjali K.,
Campbell Megan J.,
Rice John P.,
Todd Richard D.,
Heath Andrew C.,
Goate Alison M.,
Peltonen Leena,
Kaprio Jaakko,
Martin Nicholas G.,
Madden Pamela A.F.
Publication year - 2009
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30924
Subject(s) - heritability , linkage (software) , genetic linkage , twin study , microsatellite , genetics , lod score , chromosome , biology , gene , gene mapping , allele
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. © 2009 Wiley‐Liss, Inc.