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The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes
The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.
ADHD, association study, dopamine, noradrenaline, serotonin, candidate gene, linkage disequilibrium
1359-4184
934-953
Brookes, K
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Zhou, K
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Buschgens, C
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Butler, L
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Brookes, K, Xu, X, Chen, W, Zhou, K, Neale, B, Lowe, N, Aneey, R, Franke, B, Gill, M, Ebstein, R, Buitelaar, J, Sham, P, Campbell, D, Knight, J, Andreou, P, Altink, M, Arnold, R, Boer, F, Buschgens, C, Butler, L, Christiansen, H, Feldman, L, Fleischman, K, Fliers, E, Howe-Forbes, R, Goldfarb, A, Heise, A, Gabriels, I, Korn-Lubetzki, I, Marco, R, Medad, S, Minderaa, R, Mulas, F, Mullerq, U, Mulligan, A, Rabin, K, Rommelse, N, Sethna, V, Sorohan, J, Uebel, H, Psychogiou, L, Weeks, A, Barrett, R, Craig, I, Banaschewski, T, Sonuga-Barke, E, Eisenberg, J, Kuntsi, J, Manor, I, McGuffin, P, Miranda, A, Oades, RD, Plomin, R, Roeyers, H, Rothenberger, A, Sergeant, J, Steinhausen, HC, Taylor, E, Faraone, SV, Asherson, P and Johannson, L (2006) The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes. Molecular Psychiatry, 11, 934-953. (doi:10.1038/sj.mp.4001869).

Record type: Article

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.

Full text not available from this repository.

More information

Published date: 8 August 2006
Keywords: ADHD, association study, dopamine, noradrenaline, serotonin, candidate gene, linkage disequilibrium

Identifiers

Local EPrints ID: 54640
URI: http://eprints.soton.ac.uk/id/eprint/54640
ISSN: 1359-4184
PURE UUID: 4fcf0059-17cb-4562-9b20-a3f0afbe3a4e

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Date deposited: 29 Jul 2008
Last modified: 13 Mar 2019 20:38

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Contributors

Author: K Brookes
Author: X Xu
Author: W Chen
Author: K Zhou
Author: B Neale
Author: N Lowe
Author: R Aneey
Author: B Franke
Author: M Gill
Author: R Ebstein
Author: J Buitelaar
Author: P Sham
Author: D Campbell
Author: J Knight
Author: P Andreou
Author: M Altink
Author: R Arnold
Author: F Boer
Author: C Buschgens
Author: L Butler
Author: H Christiansen
Author: L Feldman
Author: K Fleischman
Author: E Fliers
Author: R Howe-Forbes
Author: A Goldfarb
Author: A Heise
Author: I Gabriels
Author: I Korn-Lubetzki
Author: R Marco
Author: S Medad
Author: R Minderaa
Author: F Mulas
Author: U Mullerq
Author: A Mulligan
Author: K Rabin
Author: N Rommelse
Author: V Sethna
Author: J Sorohan
Author: H Uebel
Author: L Psychogiou
Author: A Weeks
Author: R Barrett
Author: I Craig
Author: T Banaschewski
Author: E Sonuga-Barke
Author: J Eisenberg
Author: J Kuntsi
Author: I Manor
Author: P McGuffin
Author: A Miranda
Author: RD Oades
Author: R Plomin
Author: H Roeyers
Author: A Rothenberger
Author: J Sergeant
Author: HC Steinhausen
Author: E Taylor
Author: SV Faraone
Author: P Asherson
Author: L Johannson

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