Document Detail

Polygenic risk and the developmental progression to heavy, persistent smoking and nicotine dependence: evidence from a 4-decade longitudinal study.
MedLine Citation:
PMID:  23536134     Owner:  NLM     Status:  MEDLINE    
IMPORTANCE: Genome-wide hypothesis-free discovery methods have identified loci that are associated with heavy smoking in adulthood. Research is needed to understand developmental processes that link newly discovered genetic risks with adult heavy smoking.
OBJECTIVE: To test how genetic risks discovered in genome-wide association studies of adult smoking influence the developmental progression of smoking behavior from initiation through conversion to daily smoking, progression to heavy smoking, nicotine dependence, and struggles with cessation.
DESIGN: A 38-year, prospective, longitudinal study of a representative birth cohort.
SETTING: The Dunedin Multidisciplinary Health and Development Study of New Zealand.
PARTICIPANTS: The study included 1037 male and female participants.
EXPOSURE: We assessed genetic risk with a multilocus genetic risk score. The genetic risk score was composed of single-nucleotide polymorphisms identified in 3 meta-analyses of genome-wide association studies of smoking quantity phenotypes.
MAIN OUTCOMES AND MEASURES: Smoking initiation, conversion to daily smoking, progression to heavy smoking, nicotine dependence (Fagerström Test of Nicotine Dependence), and cessation difficulties were evaluated at 8 assessments spanning the ages of 11 to 38 years.
RESULTS: Genetic risk score was unrelated to smoking initiation. However, individuals at higher genetic risk were more likely to convert to daily smoking as teenagers, progressed more rapidly from smoking initiation to heavy smoking, persisted longer in smoking heavily, developed nicotine dependence more frequently, were more reliant on smoking to cope with stress, and were more likely to fail in their cessation attempts. Further analysis revealed that 2 adolescent developmental phenotypes-early conversion to daily smoking and rapid progression to heavy smoking-mediated associations between the genetic risk score and mature phenotypes of persistent heavy smoking, nicotine dependence, and cessation failure. The genetic risk score predicted smoking risk over and above family history.
CONCLUSIONS AND RELEVANCE: Initiatives that disrupt the developmental progression of smoking behavior among adolescents may mitigate genetic risks for developing adult smoking problems. Future genetic research may maximize discovery potential by focusing on smoking behavior soon after smoking initiation and by studying young smokers.
Daniel W Belsky; Terrie E Moffitt; Timothy B Baker; Andrea K Biddle; James P Evans; HonaLee Harrington; Renate Houts; Madeline Meier; Karen Sugden; Benjamin Williams; Richie Poulton; Avshalom Caspi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  JAMA psychiatry     Volume:  70     ISSN:  2168-6238     ISO Abbreviation:  JAMA Psychiatry     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-02     Completed Date:  2013-06-27     Revised Date:  2014-06-25    
Medline Journal Info:
Nlm Unique ID:  101589550     Medline TA:  JAMA Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  534-42     Citation Subset:  AIM; IM    
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MeSH Terms
Adolescent Development / drug effects,  physiology
Child, Preschool
Cohort Studies
Disease Progression
Longitudinal Studies
New Zealand / epidemiology
Smoking / epidemiology,  genetics*,  pathology
Time Factors
Tobacco Use Disorder / epidemiology,  genetics*,  pathology
Young Adult
Grant Support
1K05CA139871/CA/NCI NIH HHS; 1R36HS020524-01/HS/AHRQ HHS; AG032282/AG/NIA NIH HHS; G0101483//Medical Research Council; G0601483//Medical Research Council; L60 MD007327/MD/NIMHD NIH HHS; MH077874/MH/NIMH NIH HHS; MR/K00381X/1//Medical Research Council; P30 DA023026/DA/NIDA NIH HHS; P30DA023026/DA/NIDA NIH HHS; R01 AG032282/AG/NIA NIH HHS; R24 HD065563/HD/NICHD NIH HHS; R36 HS020524/HS/AHRQ HHS; T32 AG000029/AG/NIA NIH HHS; T32-AG000029/AG/NIA NIH HHS

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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