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QTL association analysis of the DRD4 exon 3 VNTR polymorphism in a population sample of children screened with a parent rating scale for ADHD symptoms

Authors

  • Dr. Sarah Curran,

    Corresponding author
    1. Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, United Kingdom
    2. Department of Child and Adolescent Psychiatry, GKT Medical School, London, United Kingdom
    • Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, U.K.
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  • J. Mill,

    1. Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, United Kingdom
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  • P. Sham,

    1. Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, United Kingdom
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  • F. Rijsdijk,

    1. Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, United Kingdom
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  • K. Marusic,

    1. Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, United Kingdom
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  • E. Taylor,

    1. Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, United Kingdom
    2. Department of Child and Adolescent Psychiatry, GKT Medical School, London, United Kingdom
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  • P. Asherson

    1. Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, United Kingdom
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Abstract

Current developments in molecular genetics have led to a rapid increase in research aimed at the identification of genetic variation that influences complex human phenotypes. One phenotype that has aroused a great deal of interest is the behavioral trait hyperactivity and the related clinical disorder attention-deficit hyperactivity disorder (ADHD). The driving force behind the molecular genetic research in this area is the overwhelming evidence from quantitative genetic studies that show high heritablility (h2 = 0.7–0.9) for the behaviors characterizing the diagnosis of ADHD, whether the disorder is viewed as a categorical entity or a continuous trait. To date, molecular studies have aimed at identifying susceptibility genes for ADHD, defined using operational diagnostic criteria, and have focused on variation within genes that regulate dopamine neurotransmission. Several studies report ADHD to be associated with the 7-repeat allele of a 48 bp repeat polymorphism (DRD4–7) in exon 3 of the dopamine D4 receptor gene (DRD4). In this study, we take a dimensional perspective of ADHD and examine the relationship of this DRD4 polymorphism in a sample of children selected from the general population on the basis of high and low scores on the five ADHD items of the Strengths and Difficulties Questionnaire (SDQ) as rated by their parents. We found a significant relationship between DRD4–7 and high-scoring individuals [chi-square = 8.63; P = 0.003; OR = 2.09 (95% CI 1.24 < OR < 3.54), F-statistic = 7.245; P = 0.008]. © 2001 Wiley-Liss, Inc.

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