title: Maternal alcohol use disorder and offspring ADHD: disentangling genetic and environmental effects using a children-of-twins design.
abstract: BACKGROUND
  Children of alcoholics are significantly more likely to experience high-risk environmental exposures, including prenatal substance exposure, and are more likely to exhibit externalizing problems [e.g. attention deficit hyperactivity disorder (ADHD)]. While there is evidence that genetic influences and prenatal nicotine and/or alcohol exposure play separate roles in determining risk of ADHD, little has been done on determining the joint roles that genetic risk associated with maternal alcohol use disorder (AUD) and prenatal risk factors play in determining risk of ADHD.
  
  
  METHODS
  Using a children-of-twins design, diagnostic telephone interview data from high-risk families (female monozygotic and dizygotic twins concordant or discordant for AUD as parents) and control families targeted from a large Australian twin cohort were analyzed using logistic regression models.
  
  
  RESULTS
  Offspring of twins with a history of AUD, as well as offspring of non-AUD monozygotic twins whose co-twin had AUD, were significantly more likely to exhibit ADHD than offspring of controls. This pattern is consistent with a genetic explanation for the association between maternal AUD and increased offspring risk of ADHD. Adjustment for prenatal smoking, which remained significantly predictive, did not remove the significant genetic association between maternal AUD and offspring ADHD.
  
  
  CONCLUSIONS
  While maternal smoking during pregnancy probably contributes to the association between maternal AUD and offspring ADHD risk, the evidence for a significant genetic correlation suggests: (i) pleiotropic genetic effects, with some genes that influence risk of AUD also influencing vulnerability to ADHD; or (ii) ADHD is a direct risk-factor for AUD.
authors.affiliation: Center for Alcohol and Addiction Studies, Department of Community Health, Brown University Medical School, Providence, RI 02912, USA. Valerie_Knopik@brown.edu
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Knopik
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Heath
authors.forename: Theodore
authors.initials: T
authors.lastname: Jacob
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Slutske
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Bucholz
authors.forename: Pamela A F
authors.initials: PA
authors.lastname: Madden
authors.forename: Mary
authors.initials: M
authors.lastname: Waldron
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000453:epidemiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology*; D002648:Child; D016241:Child of Impaired Parents / Q000523:psychology / Q000706:statistics & numerical data*; D004777:Environment; D005260:Female; D006801:Humans; D008297:Male; D008425:Maternal Behavior / Q000523:psychology*; D009035:Mothers / Q000706:statistics & numerical data*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014427:Twins / Q000235:genetics*