 |
|
A Common Haplotype of the Dopamine Transporter Gene Associated With Attention-Deficit/Hyperactivity Disorder and Interacting With Maternal Use of Alcohol During Pregnancy
Keeley-Joanne Brookes, BSc;
Jon Mill, PhD;
Camilla Guindalini, BSc;
Sarah Curran, MRCPsych, PhD;
Xiaohui Xu, MD;
Jo Knight, PhD;
Chih-Ken Chen, MD, PhD;
Yu-Shu Huang, MD;
Vaheshta Sethna, BSc;
Eric Taylor, FRCP, FRCPsych, PhD;
Wai Chen, MRCPsych;
Gerome Breen, PhD;
Philip Asherson, MRCPsych, PhD
Arch Gen Psychiatry. 2006;63:74-81.
Context Attention-deficit/hyperactivity disorder (ADHD) is a common heritable childhood behavioral disorder. Identifying risk factors for ADHD may lead to improved intervention and prevention. The dopamine transporter gene (DAT1) is associated with ADHD in several studies, with an average 1.2 odds ratio and evidence of heterogeneity across data sets.
Objective To investigate sources of heterogeneity by refining the DAT1 association using additional markers and investigating gene-environment interaction between DAT1 and maternal use of alcohol and tobacco during pregnancy.
Design Prospective study.
Setting and Patients Children with ADHD from child behavior clinics in the southeast of England and in the Taipei area of Taiwan.
Interventions Within-family tests of association using 2 repeat polymorphisms in the 3' untranslated region and intron 8 plus additional markers in the English sample.
Main Outcome Measures Transmission ratios of risk alleles from heterozygote parents to affected offspring and comparison of the transmission ratios in high- and low-exposure groups for the environmental variables.
Results A novel association was identified between ADHD, the intron 8 polymorphism, and a specific risk haplotype in both English and Taiwanese samples. The risk haplotype showed significant interactions with maternal use of alcohol during pregnancy.
Conclusions The identification of a common haplotype in 2 independent populations is an important step toward identifying functionally significant regions of DAT1. Interaction between DAT1 genotypes and maternal use of alcohol during pregnancy suggests that DAT1 moderates the environmental risk and has implications for the prevention of ADHD. Further studies are required to delineate the precise causal risk factor involved in this interaction.
Author Affiliations: Medical Research Council Social Genetic Developmental Psychiatry Centre, Institute of Psychiatry, London, England (Mss Brookes, Guindalini, and Sethna and Drs Mill, Curran, Xu, Knight, W. Chen, Taylor, Breen, and Asherson); and Department of Psychiatry, Chang Gung Memorial Hospital, Taipei, Taiwan (Drs C.-K. Chen and Huang).
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Dopaminergic Haplotype as a Predictor of Spatial Inattention in Children With Attention-Deficit/Hyperactivity Disorder
Bellgrove et al.
Arch Gen Psychiatry 2009;66:1135-1142.
ABSTRACT
| FULL TEXT
Binge Pattern of Alcohol Consumption During Pregnancy and Childhood Mental Health Outcomes: Longitudinal Population-Based Study
Sayal et al.
Pediatrics 2009;123:e289-e296.
ABSTRACT
| FULL TEXT
Review: Genetics of Attention Deficit/Hyperactivity Disorder
Wallis et al.
J Pediatr Psychol 2008;33:1085-1099.
ABSTRACT
| FULL TEXT
Environmental Risk Factors and Attention-Deficit/Hyperactivity Disorder Symptoms--Reply
Laucht et al.
Arch Gen Psychiatry 2008;65:357-358.
FULL TEXT
The Historical Significance of Ebaugh's 1923 Article: A Commentary
Barkley
J Atten Disord 2007;11:339-340.
Causal Inferences Regarding Prenatal Alcohol Exposure and Childhood Externalizing Problems
D'Onofrio et al.
Arch Gen Psychiatry 2007;64:1296-1304.
ABSTRACT
| FULL TEXT
Interacting Effects of the Dopamine Transporter Gene and Psychosocial Adversity on Attention-Deficit/Hyperactivity Disorder Symptoms Among 15-Year-Olds From a High-Risk Community Sample
Laucht et al.
Arch Gen Psychiatry 2007;64:585-590.
ABSTRACT
| FULL TEXT
Confirmation That a Specific Haplotype of the Dopamine Transporter Gene Is Associated With Combined-Type ADHD
Asherson et al.
Am. J. Psychiatry 2007;164:674-677.
ABSTRACT
| FULL TEXT
Prenatal Alcohol Exposure and Gender Differences in Childhood Mental Health Problems: A Longitudinal Population-Based Study
Sayal et al.
Pediatrics 2007;119:e426-e434.
ABSTRACT
| FULL TEXT
Evidence-based guidelines for management of attention-deficit/hyperactivity disorder in adolescents in transition to adult services and in adults: recommendations from the British Association for Psychopharmacology
Nutt et al.
J Psychopharmacol 2007;21:10-41.
ABSTRACT
Gene-environment interplay in attention-deficit hyperactivity disorder and the importance of a developmental perspective
THAPAR et al.
Br. J. Psychiatry 2007;190:1-3.
ABSTRACT
| FULL TEXT
Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD)
Li et al.
Hum Mol Genet 2006;15:2276-2284.
ABSTRACT
| FULL TEXT
|
