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A Family Based Association Study of DRD4, DAT1, and 5HTT and Continuous Traits of Attention-Deficit Hyperactivity Disorder

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Abstract

Despite its high heritability, genetic association studies of attention deficit-hyperactivity disorder (ADHD) have often resulted in somewhat small, inconsistent effects. Refining the ADHD phenotype beyond a dichotomous diagnosis and testing associations with continuous information from the underlying symptom dimensions may result in more consistent genetic findings. This study further examined the association between ADHD and the DRD4, DAT1, and 5HTT genes by testing their association with multivariate phenotypes derived from continuous measures of ADHD symptom severity. DNA was collected in 202 families consisting of at least one ADHD proband and at least one parent or sibling. VNTR polymorphisms of the DRD4 and DAT1 genes were significantly associated with the continuous ADHD phenotype. The association with DRD4 was driven by both inattentive and hyperactive symptoms, while the association with DAT1 was driven primarily by inattentive symptoms. These results use novel methods to build upon important connections between dopamine genes and their final behavioral manifestation as symptoms of ADHD.

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Acknowledgements

This research was supported by NICHD center grant P50 HD-27802 (Center Director: R. K. Olson). The first author was also supported in part during the preparation of this manuscript by NIH grants R01 MH62120, and R01 MH63941 (E.G. Willcutt) and F31 MH078514 (L.C. Bidwell). We extend our deepest gratitude to the Colorado Learning Disabilities Research Center staff and the school personnel and families that participated in the study.

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Authors and Affiliations

  1. Department of Psychiatry and Human Behavior, Brown University, Box G-S121-4, Providence, RI, 02912, USA

    L. Cinnamon Bidwell

  2. Department of Psychology, University of Colorado, Boulder, CO, USA

    Erik G. Willcutt, Matthew B. McQueen, John C. DeFries & Richard K. Olson

  3. Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA

    Erik G. Willcutt, Matthew B. McQueen, John C. DeFries, Richard K. Olson & Bruce F. Pennington

  4. Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA

    Shelley D. Smith

  5. Department of Psychology, University of Denver, Denver, CO, USA

    Bruce F. Pennington

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  1. L. Cinnamon Bidwell
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  2. Erik G. Willcutt
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  4. John C. DeFries
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Correspondence to L. Cinnamon Bidwell.

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Bidwell, L.C., Willcutt, E.G., McQueen, M.B. et al. A Family Based Association Study of DRD4, DAT1, and 5HTT and Continuous Traits of Attention-Deficit Hyperactivity Disorder. Behav Genet 41, 165–174 (2011). https://doi.org/10.1007/s10519-010-9437-y

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