We will seek to definitively clarify the relationship between maternal cigarette smoking during pregnancy and subsequent offspring smoking behaviour, and specifically identify any critical risk periods during pregnancy when nicotine exposure is associated with increased risk of offspring smoking.

We will use biochemical validation of smoking and both maternal and offspring genotype to accurately characterise foetal nicotine exposure and validate offspring smoking status, and to determine whether the association of nicotine exposure with subsequent smoking behaviour is explained by, or moderated by transmitted genotype.

We will assess offspring's response to first cigarette to investigate whether any association between foetal nicotine exposure and subsequent smoking behaviour is mediated by sensitivity to nicotine.

Specific research questions:

1. Is there an association between foetal nicotine exposure and subsequent offspring smoking behaviour, in particular initiation?

2. Is variation in nAChR and CYP2A6 genotype associated with subsequent offspring smoking behaviour?

3. Is any observed association between foetal nicotine exposure and offspring smoking explained by transmission of nAChR and CYP2A6 genotypes?

4. Does variation in nAChR and CYP2A6 genotype moderate the association of foetal nicotine exposure and offspring smoking behaviour?

5. Is any association betwee foetal nicotine exposure and/or genotype and subsequent offspring smoking behaviour mediated by subjective response to first cigarette?

Existing Data:

Maternal self-reported smoking status (pregnancy-15 years)

Paternal self-reported smoking status (pregnancy-15 years)

Offspring self-reported smoking status (11-15 years)

Offspring self-report subjective experience of first cigarette (15 years)

Maternal DNA

Offspring DNA

New Data:

Maternal self-reported smoking status (17 years)

Paternal self-reported smoking status (17 years)

Offspring self-reported smoking status (17 years)

Maternal urinary cotinine assay (pregnancy)

Offspring urinary cotinine assay (11-17 years)