Association of the paternally transmitted copy of common Valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to ADHD

L. Kent, E Green, Z. Hawi, A. Kirley, F. Dudbridge, N. Lowe, R. Raybould, Kate Langley, N. Bray, M Fitzgerald, Michael J Owen, M. C. O'Donovan, Michael Gill, A. Thapar, N. Craddock

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable, neurodevelopmental disorder with onset in early childhood. Genes involved in neuronal development and growth are, thus, important etiological candidates and brain-derived neurotrophic factor (BDNF), has been hypothesized to play a role in the pathogenesis of ADHD. BDNF is a member of the neurotrophin family and is involved in the survival and differentiation of dopaminergic neurons in the developing brain (of relevance because drugs that block the dopamine transporter can be effective therapeutically). The common Val66Met functional polymorphism in the human BDNF gene (rs 6265) was genotyped in a collaborative family-based sample of 341 white UK or Irish ADHD probands and their parents. We found evidence for preferential transmission of the valine (G) allele of BDNF (odds ratio, OR = 1.6, P = 0.02) with a strong paternal effect (paternal transmissions: OR = 3.2, P = 0.0005; maternal transmissions: OR = 1.00; P = 1.00). Our findings support the hypothesis that BDNF is involved in the pathogenesis of ADHD. The transmission difference between parents raises the possibility that an epigenetic process may be involved.
Original languageEnglish
Pages (from-to)939-943
Number of pages5
JournalMolecular Psychiatry
Volume10
Issue number10
DOIs
Publication statusPublished - Oct 2005
Externally publishedYes

Keywords

  • Association study
  • Attention deficit hyperactivity disorder
  • Neurotrophic factor
  • Polymorphism

Cite this

Kent, L. ; Green, E ; Hawi, Z. ; Kirley, A. ; Dudbridge, F. ; Lowe, N. ; Raybould, R. ; Langley, Kate ; Bray, N. ; Fitzgerald, M ; Owen, Michael J ; O'Donovan, M. C. ; Gill, Michael ; Thapar, A. ; Craddock, N. / Association of the paternally transmitted copy of common Valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to ADHD. In: Molecular Psychiatry. 2005 ; Vol. 10, No. 10. pp. 939-943.
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title = "Association of the paternally transmitted copy of common Valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to ADHD",
abstract = "Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable, neurodevelopmental disorder with onset in early childhood. Genes involved in neuronal development and growth are, thus, important etiological candidates and brain-derived neurotrophic factor (BDNF), has been hypothesized to play a role in the pathogenesis of ADHD. BDNF is a member of the neurotrophin family and is involved in the survival and differentiation of dopaminergic neurons in the developing brain (of relevance because drugs that block the dopamine transporter can be effective therapeutically). The common Val66Met functional polymorphism in the human BDNF gene (rs 6265) was genotyped in a collaborative family-based sample of 341 white UK or Irish ADHD probands and their parents. We found evidence for preferential transmission of the valine (G) allele of BDNF (odds ratio, OR = 1.6, P = 0.02) with a strong paternal effect (paternal transmissions: OR = 3.2, P = 0.0005; maternal transmissions: OR = 1.00; P = 1.00). Our findings support the hypothesis that BDNF is involved in the pathogenesis of ADHD. The transmission difference between parents raises the possibility that an epigenetic process may be involved.",
keywords = "Association study, Attention deficit hyperactivity disorder, Neurotrophic factor, Polymorphism",
author = "L. Kent and E Green and Z. Hawi and A. Kirley and F. Dudbridge and N. Lowe and R. Raybould and Kate Langley and N. Bray and M Fitzgerald and Owen, {Michael J} and O'Donovan, {M. C.} and Michael Gill and A. Thapar and N. Craddock",
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doi = "10.1038/sj.mp.4001696",
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Kent, L, Green, E, Hawi, Z, Kirley, A, Dudbridge, F, Lowe, N, Raybould, R, Langley, K, Bray, N, Fitzgerald, M, Owen, MJ, O'Donovan, MC, Gill, M, Thapar, A & Craddock, N 2005, 'Association of the paternally transmitted copy of common Valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to ADHD', Molecular Psychiatry, vol. 10, no. 10, pp. 939-943. https://doi.org/10.1038/sj.mp.4001696

Association of the paternally transmitted copy of common Valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to ADHD. / Kent, L.; Green, E; Hawi, Z.; Kirley, A.; Dudbridge, F.; Lowe, N.; Raybould, R.; Langley, Kate; Bray, N.; Fitzgerald, M; Owen, Michael J; O'Donovan, M. C.; Gill, Michael; Thapar, A.; Craddock, N.

In: Molecular Psychiatry, Vol. 10, No. 10, 10.2005, p. 939-943.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Association of the paternally transmitted copy of common Valine allele of the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with susceptibility to ADHD

AU - Kent, L.

AU - Green, E

AU - Hawi, Z.

AU - Kirley, A.

AU - Dudbridge, F.

AU - Lowe, N.

AU - Raybould, R.

AU - Langley, Kate

AU - Bray, N.

AU - Fitzgerald, M

AU - Owen, Michael J

AU - O'Donovan, M. C.

AU - Gill, Michael

AU - Thapar, A.

AU - Craddock, N.

PY - 2005/10

Y1 - 2005/10

N2 - Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable, neurodevelopmental disorder with onset in early childhood. Genes involved in neuronal development and growth are, thus, important etiological candidates and brain-derived neurotrophic factor (BDNF), has been hypothesized to play a role in the pathogenesis of ADHD. BDNF is a member of the neurotrophin family and is involved in the survival and differentiation of dopaminergic neurons in the developing brain (of relevance because drugs that block the dopamine transporter can be effective therapeutically). The common Val66Met functional polymorphism in the human BDNF gene (rs 6265) was genotyped in a collaborative family-based sample of 341 white UK or Irish ADHD probands and their parents. We found evidence for preferential transmission of the valine (G) allele of BDNF (odds ratio, OR = 1.6, P = 0.02) with a strong paternal effect (paternal transmissions: OR = 3.2, P = 0.0005; maternal transmissions: OR = 1.00; P = 1.00). Our findings support the hypothesis that BDNF is involved in the pathogenesis of ADHD. The transmission difference between parents raises the possibility that an epigenetic process may be involved.

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