DRD4 and DAT1 in ADHD: functional neurobiology to pharmacogenetics
DRD4 and DAT1 in ADHD: functional neurobiology to pharmacogenetics
Attention deficit/hyperactivity disorder (ADHD) is a common and potentially very impairing neuropsychiatric disorder of childhood. Statistical genetic studies of twins have shown ADHD to be highly heritable, with the combination of genes and gene by environment interactions accounting for around 80% of phenotypic variance. The initial molecular genetic studies where candidates were selected because of the efficacy of dopaminergic compounds in the treatment of ADHD were remarkably successful and provided strong evidence for the role of DRD4 and DAT1 variants in the pathogenesis of ADHD. However, the recent application of noncandidate gene strategies (eg, genome-wide association scans) has failed to identify additional genes with substantial genetic main effects, and the effects for DRD4 and DAT1 have not been replicated. This is the usual pattern observed for most other physical and mental disorders evaluated with current state-of-the-art methods. In this paper we discuss future strategies for genetic studies in ADHD, highlighting both the pitfalls and possible solutions relating to candidate gene studies, genome-wide studies, defining the phenotype, and statistical approaches.
61-78
Turic, D.
492e37c3-c13b-4c7e-a73f-076525e9e3f1
Swanson, J.
9f40e6c3-1eef-4011-b72a-f76161610c06
Sonuga-Barke, Edmund J.S.
bc80bf95-6cf9-4c76-a09d-eaaf0b717635
May 2010
Turic, D.
492e37c3-c13b-4c7e-a73f-076525e9e3f1
Swanson, J.
9f40e6c3-1eef-4011-b72a-f76161610c06
Sonuga-Barke, Edmund J.S.
bc80bf95-6cf9-4c76-a09d-eaaf0b717635
Turic, D., Swanson, J. and Sonuga-Barke, Edmund J.S.
(2010)
DRD4 and DAT1 in ADHD: functional neurobiology to pharmacogenetics.
Pharmacogenetics and Personalized Medicine, 2010 (3), .
(doi:10.2147/PGPM.S6800).
Abstract
Attention deficit/hyperactivity disorder (ADHD) is a common and potentially very impairing neuropsychiatric disorder of childhood. Statistical genetic studies of twins have shown ADHD to be highly heritable, with the combination of genes and gene by environment interactions accounting for around 80% of phenotypic variance. The initial molecular genetic studies where candidates were selected because of the efficacy of dopaminergic compounds in the treatment of ADHD were remarkably successful and provided strong evidence for the role of DRD4 and DAT1 variants in the pathogenesis of ADHD. However, the recent application of noncandidate gene strategies (eg, genome-wide association scans) has failed to identify additional genes with substantial genetic main effects, and the effects for DRD4 and DAT1 have not been replicated. This is the usual pattern observed for most other physical and mental disorders evaluated with current state-of-the-art methods. In this paper we discuss future strategies for genetic studies in ADHD, highlighting both the pitfalls and possible solutions relating to candidate gene studies, genome-wide studies, defining the phenotype, and statistical approaches.
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Published date: May 2010
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Local EPrints ID: 148781
URI: http://eprints.soton.ac.uk/id/eprint/148781
PURE UUID: f77a905e-24d9-4eb7-a828-3080d0621ec9
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Date deposited: 07 May 2010 09:02
Last modified: 14 Mar 2024 01:03
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Author:
D. Turic
Author:
J. Swanson
Author:
Edmund J.S. Sonuga-Barke
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