Publication: TTC12-ANKK1-DRD2 and CHRNA5-CHRNA3-CHRNB4 influence different pathways leading to smoking behavior from adolescence to mid-adulthood
Issued Date
2011-04-01
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00063223
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2-s2.0-79952569929
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Mahidol University
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SCOPUS
Bibliographic Citation
Biological Psychiatry. Vol.69, No.7 (2011), 650-660
Suggested Citation
Francesca Ducci, Marika Kaakinen, Anneli Pouta, Anna Liisa Hartikainen, Juha Veijola, Matti Isohanni, Pimphen Charoen, Lachlan Coin, Clive Hoggart, Jesper Ekelund, Leena Peltonen, Nelson Freimer, Paul Elliott, Gunter Schumann, Marjo Riitta Jürvelin TTC12-ANKK1-DRD2 and CHRNA5-CHRNA3-CHRNB4 influence different pathways leading to smoking behavior from adolescence to mid-adulthood. Biological Psychiatry. Vol.69, No.7 (2011), 650-660. doi:10.1016/j.biopsych.2010.09.055 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/12789
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Title
TTC12-ANKK1-DRD2 and CHRNA5-CHRNA3-CHRNB4 influence different pathways leading to smoking behavior from adolescence to mid-adulthood
Other Contributor(s)
King's College London
St George's University of London
Imperial College London
Medical Research Council
Wellcome Trust
Oulun Yliopisto
National Institutes of Health, Bethesda
Helsingin Yliopisto
Mahidol University
Broad Institute
University of California, Los Angeles
Jane & Terry Semel Institute for Neuroscience & Human Behavior
St George's University of London
Imperial College London
Medical Research Council
Wellcome Trust
Oulun Yliopisto
National Institutes of Health, Bethesda
Helsingin Yliopisto
Mahidol University
Broad Institute
University of California, Los Angeles
Jane & Terry Semel Institute for Neuroscience & Human Behavior
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. © 2011 Society of Biological Psychiatry.