Maternal smoking in pregnancy moderates the effect of the brain-derived neurotrophic factor (BDNF) gene polymorphism on childhood IQ across multiple ages

Maternal smoking in pregnancy has been separately linked with both lower IQ scores and epigenetic modifications of the brain-derived neurotrophic factor (BDNF) gene in offspring. The purpose of this study was to investigate whether maternal smoking exposure interacts with the BDNF single nucleotide polymorphism (SNP) rs6265 to affect offspring IQ across multiple ages during childhood. Participants are 546 members of a longitudinal study of 871 Caucasian infants sampled disproportionately for small for gestational age: approximately half had birthweight < 10th percentile when delivered at term. Perinatal events assessed here were birthweight, maternal school leaving age, and exposure to maternal smoking in-utero. Childhood factors assessed were gender, BDNF, and IQ measured at ages 3.5, 7 and 11 years (repeated measures outcome). We found a significant interaction between rs6265 genotype and maternal smoking in pregnancy on IQ scores, controlling for birthweight. IQ scores of Met-BDNF carriers were significantly lower when mothers smoked during pregnancy (over 8 IQ points) compared to when they did not. This was of borderline statistical significance when maternal school leaving age was controlled (p = 0.052).