title: Associations of prenatal nicotine exposure and the dopamine related genes ANKK1 and DRD2 to verbal language.
abstract: 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.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: Eicher
authors.forename: Natalie R
authors.initials: NR
authors.lastname: Powers
authors.forename: Kelly
authors.initials: K
authors.lastname: Cho
authors.forename: Laura L
authors.initials: LL
authors.lastname: Miller
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Mueller
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: J Bruce
authors.initials: JB
authors.lastname: Tomblin
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gruen
mesh_terms: D015331:Cohort Studies; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007802:Language; D009538:Nicotine / Q000008:administration & dosage* / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D013060:Speech
chemical_list: C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; D009538:Nicotine; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases; D004298:Dopamine