The role of nicotinic receptor genes (CHRN) in the pathways of prenatal tobacco exposure on smoking behavior among young adult light smokers

Arielle S. Selya*, Dale S. Cannon, Robert B. Weiss, Lauren S. Wakschlag, Jennifer S. Rose, Lisa Dierker, Donald Hedeker, Robin J. Mermelstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Prenatal tobacco exposure (PTE) is associated with more frequent smoking among young, light smokers. Little is known about how nicotinic acetylcholine receptor (CHRN) genes may contribute to this relationship. Methods: Data were drawn from a longitudinal cohort of young light smokers of European ancestry (N = 511). Three single nucleotide polymorphisms (SNPs) among offspring, rs16969968 and rs6495308 in CHRNA5A3B4 and rs2304297 in CHRNB3A6, were analyzed with respect to whether they 1) predict PTE status; 2) confound the previously-reported effects of PTE on future smoking; 3) have effects on youth smoking frequency that are mediated through PTE; and 4) have effects that are moderated by PTE. Results: rs2304297 and rs6495308 were associated with increased likelihood and severity of PTE, respectively. In a path analysis, rs16969968 directly predicted more frequent smoking in young adulthood (B = 1.50, p =.044); this association was independent of, and not mediated by, PTE. The risk of rs16969968 (IRR = 1.07, p =.015) and the protective effect of rs2304297 (IRR = 0.84, p <.001) on smoking frequency were not moderated by PTE. PTE moderated the effect of rs6495308, such that these alleles were protective against later smoking frequency only among non-exposed youth (IRR = 0.85, p <.001). Conclusions: The association between offspring CHRNB3A6 and PTE is a novel finding. The risk of rs16969968 on youth smoking is independent and unrelated to that of PTE among young, light smokers. PTE moderates the protective effect of rs6495308 on youth smoking frequency. However, PTE's pathway to youth smoking behavior was not explained by these genetic factors, leaving its mechanism(s) of action unclear.

Original languageEnglish (US)
Pages (from-to)231-237
Number of pages7
JournalAddictive Behaviors
StatePublished - Sep 2018


  • Genetics
  • Prenatal tobacco exposure
  • Smoking
  • Structural equation modeling

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Clinical Psychology
  • Toxicology
  • Psychiatry and Mental health

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