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No preferential transmission of paternal alleles at risk genes in attention-deficit hyperactivity disorder

Molecular Psychiatry volume 12, pages 226–229 (2007)Cite this article

Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition for which a significant genetic component has been suggested, although the mode of inheritance appears to be complex. Recently, Hawi et al.1 reported data supporting the presence of parent-of-origin effects for the transmission of risk alleles for nine dopaminergic and serotoninergic genes showing association with ADHD. After conducting a transmission/disequilibrium test (TDT) analysis, Hawi and colleagues observed an enhancement of the association findings when parental transmissions were analyzed separately, with association due principally to paternal overtransmission of risk alleles.

To verify this hypothesis, we undertook the investigation of parent-of-origin effects in an independent sample of nuclear families from the Toronto area. The characteristics of the sample, methods of assessment and inclusion/exclusion criteria have been described previously.2, 3 The number of families genotyped for each gene varied between 142 and 266 families for the different markers, dependent on the stage of family collection at the time of genotyping. We included in our analysis the genes for DAT1, DRD4, DRD5, SNAP25 and 5HT1B, since they are the most replicated genes associated with ADHD and were also tested in Hawi et al.'s study.1 For DAT1, SNAP25 and DRD5, the most significant variant in our sample was different from those previously reported by others; thus, we also included the marker/allele yielding the best P-value in our sample for these genes. Association results for these five genes using the Toronto sample have been reported fully or partially previously.4, 5, 6, 7, 8 Note that the DRD4-616 genotyping assay was redesigned and the marker reanalyzed since our original study to avoid interference in the interpretation of the results from a second polymorphism at −615. Similar to Hawi et al., we also show the results from analysis of five additional genes that demonstrated significant evidence of association in the ADHD sample from Toronto. These were the genes for dopamine receptor D1 (DRD1),9 D1-interacting protein calcyon (DRD1IP),2 α-subunit of the Gs-like protein Golf (GNAL) (Laurin et al.10), glutamate receptor 2B (GRIN2B) (Dorval et al.11) and serotonin receptor 2A (HTR2A).3 We performed a TDT analysis and analyzed transmission from mothers and fathers separately to detect any bias in parental transmission. These analyses were carried out using the extended TDT program.

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References

  1. Hawi Z, Segurado R, Conroy J, Sheehan K, Lowe N, Kirley A et al. Am J Hum Genet 2005; 77: 958–965.

  2. Laurin N, Misener VL, Crosbie J, Ickowicz A, Pathare T, Roberts W et al. Mol Psychiatry 2005; 10: 1117–1125.

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Authors and Affiliations

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

    N Laurin, Y Feng & C L Barr

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

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

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

    M Malone

  4. Ontario Institute for Studies in Education at the University of Toronto, Toronto, ON, Canada

    R Tannock

  5. 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. N Laurin
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Correspondence to C L Barr.

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Laurin, N., Feng, Y., Ickowicz, A. et al. No preferential transmission of paternal alleles at risk genes in attention-deficit hyperactivity disorder. Mol Psychiatry 12, 226–229 (2007). https://doi.org/10.1038/sj.mp.4001936

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