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  • Original Research Article
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Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD

Molecular Psychiatry volume 10, pages 944–949 (2005)Cite this article

A Corrigendum to this article was published on 26 January 2006

Abstract

Genetic and pharmacological studies have emphasised the role of serotonin 5-hydroxytryptamine (5-HT) as a possible etiologic factor in the development of attention-deficit hyperactivity disorder (ADHD). Tryptophan hydroxylase (TPH) is a rate-limiting enzyme in the biosynthesis of serotonin from tryptophan. Originally, the TPH gene was thought to be widely expressed, but a second form of TPH, TPH2, was recently identified and the TPH2 gene was found to be solely expressed in the brain. We examined eight single nucleotide polymorphisms (SNP) in the TPH2 gene for association with ADHD in 179 Irish nuclear families. Transmission disequilibrium test analysis revealed significant association between the T allele of marker rs1843809 with the disorder (χ2=12.2, P=0.0006, OR=2.36). Stratifying data by the sex of the transmitting parent showed that this association was enhanced when paternal transmission was considered (OR=3.7). In addition, several haplotypes (all including the associated marker) were associated with ADHD. These preliminary findings suggest that TPH2 is a susceptibility locus for ADHD. Further confirmation, preferably from different ethnic groups, is required to firmly implicate TPH2 in the pathophysiology of ADHD.

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Acknowledgements

We acknowledge the generous support of the Health Research Board, Dublin (KS, NL, ZH), the Dublin Molecular Medicine Centre for ZH and the Hyperactive and Attention Disorder (HAD) Group Ireland. We also thank the families that participated in the study.

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Authors and Affiliations

  1. Department of Genetics, Trinity College Dublin, Dublin, Ireland

    K Sheehan, N Lowe, M Gill & Z Hawi

  2. Department of Psychiatry, Trinity College Dublin, Dublin, Ireland

    A Kirley, C Mullins, M Fitzgerald & M Gill

Authors
  1. K Sheehan
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  2. N Lowe
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  3. A Kirley
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  4. C Mullins
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  5. M Fitzgerald
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  6. M Gill
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  7. Z Hawi
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Correspondence to Z Hawi.

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Sheehan, K., Lowe, N., Kirley, A. et al. Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD. Mol Psychiatry 10, 944–949 (2005). https://doi.org/10.1038/sj.mp.4001698

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