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

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

doi:10.1038/sj.mp.4001869

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

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

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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.

Original language	English
Pages (from-to)	934 - 953
Number of pages	20
Journal	Molecular Psychiatry
Volume	11
Issue number	10
DOIs	https://doi.org/10.1038/sj.mp.4001869
Publication status	Published - 9 Oct 2006

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Brookes, K., Xu, X., Chen, W., Zhou, K., Neale, B., Lowe, N., Aneey, R., Franke, R., Gill, M., Ebstein, R., Buitelaar, J., Sham, P., Campbell, D., Knight, J., Andreou, P., Altink, M., Arnold, R., Boer, F., Buschgens, C., ... Johansson, 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(10), 934 - 953. https://doi.org/10.1038/sj.mp.4001869

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

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.",

author = "K Brookes and X Xu and W Chen and K Zhou and B Neale and N Lowe and R Aneey and R Franke and M Gill and R Ebstein and J Buitelaar and P Sham and D Campbell and J Knight and P Andreou and M Altink and R Arnold and F Boer and C Buschgens and L Butler and H Christiansen and L Feldman and K Fleischman and E Fliers and R Howe-Forbes and A Goldfarb and A Heise and I Gabri{\"e}ls and I Korn-Lubetzki and R Marco and S Medad and R Minderaa and F Mulas and U M{\"u}ller and A Mulligan and K Rabin and N Rommelse and V Sethna and J Sorohan and H Uebel and L Psychogiou and A Weeks and R Barrett and I Craig and T Banaschewski and E Sonuga-Barke and J Eisenberg and J Kuntsi and I Manor and P McGuffin and A Miranda and R.D. Oades and R Plomin and H Roeyers and A Rothenberger and J Sergeant and H-C Steinhausen and E Taylor and M Thompson and S.V. Faraone and P Asherson and L Johansson",

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doi = "10.1038/sj.mp.4001869",

language = "English",

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journal = "Molecular Psychiatry",

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Brookes, K, Xu, X, Chen, W, Zhou, K, Neale, B, Lowe, N, Aneey, R, Franke, R, 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, Gabriëls, I, Korn-Lubetzki, I, Marco, R, Medad, S, Minderaa, R, Mulas, F, Müller, 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, H-C, Taylor, E, Thompson, M, Faraone, SV, Asherson, P & Johansson, 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, vol. 11, no. 10, pp. 934 - 953. https://doi.org/10.1038/sj.mp.4001869

TY - JOUR

T1 - The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes

AU - Brookes, K

AU - Xu, X

AU - Chen, W

AU - Zhou, K

AU - Neale, B

AU - Lowe, N

AU - Aneey, R

AU - Franke, R

AU - Gill, M

AU - Ebstein, R

AU - Buitelaar, J

AU - Sham, P

AU - Campbell, D

AU - Knight, J

AU - Andreou, P

AU - Altink, M

AU - Arnold, R

AU - Boer, F

AU - Buschgens, C

AU - Butler, L

AU - Christiansen, H

AU - Feldman, L

AU - Fleischman, K

AU - Fliers, E

AU - Howe-Forbes, R

AU - Goldfarb, A

AU - Heise, A

AU - Gabriëls, I

AU - Korn-Lubetzki, I

AU - Marco, R

AU - Medad, S

AU - Minderaa, R

AU - Mulas, F

AU - Müller, U

AU - Mulligan, A

AU - Rabin, K

AU - Rommelse, N

AU - Sethna, V

AU - Sorohan, J

AU - Uebel, H

AU - Psychogiou, L

AU - Weeks, A

AU - Barrett, R

AU - Craig, I

AU - Banaschewski, T

AU - Sonuga-Barke, E

AU - Eisenberg, J

AU - Kuntsi, J

AU - Manor, I

AU - McGuffin, P

AU - Miranda, A

AU - Oades, R.D.

AU - Plomin, R

AU - Roeyers, H

AU - Rothenberger, A

AU - Sergeant, J

AU - Steinhausen, H-C

AU - Taylor, E

AU - Thompson, M

AU - Faraone, S.V.

AU - Asherson, P

AU - Johansson, L

PY - 2006/10/9

Y1 - 2006/10/9

N2 - 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.

AB - 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.

U2 - 10.1038/sj.mp.4001869

DO - 10.1038/sj.mp.4001869

M3 - Article

VL - 11

SP - 934

EP - 953

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 10

ER -

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

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