Psychological Medicine



Original Article

Maternal alcohol use disorder and offspring ADHD: disentangling genetic and environmental effects using a children-of-twins design


VALERIE S. KNOPIK a1c1, ANDREW C. HEATH a2, THEODORE JACOB a3, WENDY S. SLUTSKE a4, KATHLEEN K. BUCHOLZ a2, PAMELA A. F. MADDEN a2, MARY WALDRON a2 and NICHOLAS G. MARTIN a5
a1 Center for Alcohol and Addiction Studies, Department of Community Health, Brown University Medical School, Providence, RI, USA
a2 Midwest Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
a3 Palo Alto Veterans Affairs Health Care System, Menlo Park, CA, USA
a4 Midwest Alcoholism Research Center, Department of Psychological Sciences, University of Missouri, Columbia, MO, USA
a5 Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Australia

Article author query
knopik vs   [PubMed][Google Scholar] 
heath ac   [PubMed][Google Scholar] 
jacob t   [PubMed][Google Scholar] 
slutske ws   [PubMed][Google Scholar] 
bucholz kk   [PubMed][Google Scholar] 
madden pa   [PubMed][Google Scholar] 
waldron m   [PubMed][Google Scholar] 
martin ng   [PubMed][Google Scholar] 

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.

Method. 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.

(Published Online May 31 2006)


Correspondence:
c1 Center for Alcohol and Addiction Studies, Department of Community Health, Brown University Medical School, Box G-BH, Providence, RI 02912, USA. (Email: Valerie_Knopik@brown.edu)


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