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Language impairment (LI) and reading disability (RD) are common pediatric neurobehavioral disorders that frequently co-occur, suggesting they share etiological determinants. Recently, our group identified prenatal nicotine exposure as a factor for RD and poor reading performance. Using smoking questionnaire and language data from the Avon Longitudinal Study of Parents and Children, we first determined if this risk could be expanded to other communication disorders by evaluating whether prenatal nicotine exposure increases risk for LI and poor performance on language tasks. Prenatal nicotine exposure increased LI risk (OR = 1.60; p = 0.0305) in a dose-response fashion with low (OR = 1.25; p = 0.1202) and high (OR = 3.84; p = 0.0002) exposures. Next, hypothesizing that the effects of prenatal nicotine may also implicate genes that function in nicotine related pathways, we determined whether known nicotine dependence (ND) genes associate with performance on language tasks. We assessed the association of 33 variants previously implicated in ND with LI and language abilities, finding association between  ANKK1 / DRD2  and performance on language tasks (p≤0.0003). The associations of markers within  ANKK1  were replicated in a separate LI case-control cohort (p<0.05). Our results show that smoking during pregnancy increases the risk for LI and poor performance on language tasks and that  ANKK1 / DRD2  contributes to language performance. More precisely, these findings suggest that prenatal environmental factors influence  in utero  development of neural circuits vital to language. Our association of  ANKK1 / DRD2  further implicates the role of nicotine-related pathways and dopamine signaling in language processing, particularly in comprehension and phonological memory.

Associations of Prenatal Nicotine Exposure and the Dopamine Related Genes ANKK1 and DRD2 to Verbal Language