TTC12-ANKK1-DRD2 and CHRNA5-CHRNA3-CHRNB4 influence different pathways leading to smoking behavior from adolescence to mid-adulthood

Ducci, Francesca, Kaakinen, Marika, Pouta, Anneli, Hartikainen, Anna-Liisa, Veijola, Juha, Isohanni, Matti, Charoen, Pimphen, Coin, Lachlan, Hoggart, Clive, Ekelund, Jesper, Peltonen, Leena, Freimer, Nelson, Elliott, Paul, Schumann, Gunter and Jurvelin, Marjo-Riitta (2011) TTC12-ANKK1-DRD2 and CHRNA5-CHRNA3-CHRNB4 influence different pathways leading to smoking behavior from adolescence to mid-adulthood. Biological Psychiatry, 69 7: 650-660. doi:10.1016/j.biopsych.2010.09.055


Author Ducci, Francesca
Kaakinen, Marika
Pouta, Anneli
Hartikainen, Anna-Liisa
Veijola, Juha
Isohanni, Matti
Charoen, Pimphen
Coin, Lachlan
Hoggart, Clive
Ekelund, Jesper
Peltonen, Leena
Freimer, Nelson
Elliott, Paul
Schumann, Gunter
Jurvelin, Marjo-Riitta
Title TTC12-ANKK1-DRD2 and CHRNA5-CHRNA3-CHRNB4 influence different pathways leading to smoking behavior from adolescence to mid-adulthood
Journal name Biological Psychiatry   Check publisher's open access policy
ISSN 0006-3223
1873-2402
Publication date 2011-04-01
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.biopsych.2010.09.055
Open Access Status Not Open Access
Volume 69
Issue 7
Start page 650
End page 660
Total pages 11
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Formatted abstract
Background: CHRNA5-CHRNA3-CHRNB4 and TTC12-ANKK1-DRD2 gene-clusters influence smoking behavior. Our aim was to test developmental changes in their effects as well as the interplays between them and with nongenetic factors.

Methods: Participants included 4762 subjects from a general population-based, prospective Northern Finland 1966 Birth Cohort (NFBC 1966). Smoking behavior was collected at age 14 and 31 years. Information on maternal smoking, socioeconomic status, and novelty seeking were also collected. Structural equation modeling was used to construct an integrative etiologic model including genetic and nongenetic factors.

Results: Several single nucleotide polymorphisms in both gene-clusters were significantly associated with smoking. The most significant were in CHRNA3 (rs1051730, p = 1.1 × 10-5) and in TTC12 (rs10502172, p = 9.1 × 10-6). CHRNA3-rs1051730[A] was more common among heavy/regular smokers than nonsmokers with similar effect-sizes at age 14 years (odds ratio [95% CI]: 1.27 [1.06-1.52]) and 31 years (1.28 [1.13-1.44]). TTC12-rs10502172[G] was more common among smokers than nonsmokers with stronger association at 14 years (1.33 [1.11-1.60]) than 31 years (1.14 [1.02-1.28]). In adolescence, carriers of three-four risk alleles at either CHRNA3-rs1051730 or TTC12-rs10502172 had almost threefold odds of smoking regularly than subjects with no risk alleles. TTC12-rs10502172 effect on smoking in adulthood was mediated by its effect on smoking in adolescence and via novelty seeking. Effect of CHRNA3-rs1051730 on smoking in adulthood was direct.

Conclusions: TTC12-ANKK1-DRD2s seemed to influence smoking behavior mainly in adolescence, and its effect is partially mediated by personality characteristics promoting drug-seeking behavior. In contrast, CHRNA5-CHRNA3-CHRNB4 is involved in the transition toward heavy smoking in mid-adulthood and in smoking persistence. Factors related to familial and social disadvantages were strong independent predictors of smoking. 
Keyword Adolescence
ANKK1
CHRNA3
CHRNA5
CHRNB4
DRD2
Gene
Nicotine
Smoking
TTC12
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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