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Glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene as a positional candidate for attention-deficit/hyperactivity disorder in the 16p13 region

Molecular Psychiatry volume 9, pages 494–499 (2004)Cite this article

Abstract

The glutamate system may be involved in the development of attention-deficit/hyperactivity disorder (ADHD) based on animal models and the role of N-methyl-D-aspartate receptors (NMDAR) in cognition and motor processes. A follow-up study of the first genome scan for ADHD identified significant evidence for linkage to the 16p13 region.1 The glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene that encodes the 2A subunit of the NMDA receptor, resides in this region and a recent study has reported an association between this gene and ADHD.2 We tested for linkage between the alleles and haplotypes of four polymorphisms at the GRIN2A locus and ADHD in our sample of 183 nuclear families with 229 affected children. In contrast to previous findings, we did not identify any evidence for a relationship of these markers and ADHD. Owing to the role of GRIN2A in aspects of cognition, we investigated the relationship of this gene to the cognitive phenotypes of inhibitory control, verbal short-term memory and verbal working memory. There was no significant evidence of linkage between GRIN2A and these phenotypes. While the results were not significant in our sample, the previous association finding suggests that further study of this gene is warranted.

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Acknowledgements

This work was supported by grants from the Natural Sciences and Engineering Research Council (JHA), The Hospital for Sick Children Psychiatric Endowment Fund (CLB), the Canadian Institutes of Health Research MT14336 (CLB) and MOP-14336 (CLB). Also, we thank Drs Anita Thapar and Michael O'Donovan for providing information on the Grin2a-5 polymorphism prior to publication.

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Authors and Affiliations

  1. Cell and Molecular Biology Division, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada

    J Adams, K Wigg & C L Barr

  2. Department of Psychiatry, Brain and Behaviour Programme, The Hospital for Sick Children, Toronto, ON, Canada

    J Crosbie, A Ickowicz, T Pathare, R Schachar, R Tannock & C L Barr

  3. Division of Neurology, Brain and Behaviour Programme, The Hospital for Sick Children, Toronto, ON, Canada

    W Roberts & M Malone

  4. Department of Psychiatry, Neurogenetics Section, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada

    J L Kennedy

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  1. J Adams
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Correspondence to C L Barr.

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Adams, J., Crosbie, J., Wigg, K. et al. Glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene as a positional candidate for attention-deficit/hyperactivity disorder in the 16p13 region. Mol Psychiatry 9, 494–499 (2004). https://doi.org/10.1038/sj.mp.4001455

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  • DOI: https://doi.org/10.1038/sj.mp.4001455

Keywords

  • ADHD
  • genetics
  • glutamate
  • GRIN2A
  • NMDA
  • linkage

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