Examining for association between candidate gene polymorphisms in the dopamine pathway and attention-deficit hyperactivity disorder: a family-based study

Payton, A., Holmes, J., Barrett, J. H., Hever, T., Fitzpatrick, H., Trumper, A. L., Harrington, R., O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Ollier, W., Worthington, J. and Thapar, Anita ORCID: https://orcid.org/0000-0002-3689-737X 2001. Examining for association between candidate gene polymorphisms in the dopamine pathway and attention-deficit hyperactivity disorder: a family-based study. Neuroscience Letters 105 (5) , pp. 464-470. 10.1002/ajmg.1407

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Abstract

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable childhood-onset psychiatric condition characterized by developmentally inappropriate inattention, hyperactivity, and impulsiveness. The pathophysiology of ADHD is currently unknown. However, the therapeutic effects of stimulant medication together with findings from animal and neuroimaging studies as well as from several molecular genetic studies of the dopamine receptor D4 gene and dopamine transporter gene have implicated involvement of the dopaminergic system. To test the dopaminergic hypothesis further, we have looked for association between ADHD and alleles of seven dopamine-related candidate genes using a family-based association approach in a sample of 150 children diagnosed with ADHD. We tested polymorphisms in genes encoding three dopamine receptors (DRD3, DRD4, and DRD5) and four dopamine-relevant enzymes: tyrosine hydroxylase [tyrosine hydroxylase (TH)], dopamine beta hydroxylase (DbetaH), catechol-O-methyltransferase (COMT), and monoamine oxidase A (MAOA). We were unable to detect a significant association with any of the polymorphisms genotyped, although there was a trend for preferential transmission of the DRD5 148 bp marker allele and the MAOA 122 bp marker allele. We conclude that none of the alleles we have tested makes a major contribution to ADHD, although much larger samples are required to exclude small effects.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	attention-deficit hyperactivity disorder; kyperkinetic disorder; genetics; association study
Publisher:	New York
ISSN:	0148-7299
Last Modified:	31 Oct 2022 09:21
URI:	https://orca.cardiff.ac.uk/id/eprint/80725

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