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The role of ASTN2 variants in childhood and adult ADHD, comorbid disorders and associated personality traits

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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Abstract

Previous linkage and genome wide association (GWA) studies in ADHD indicated astrotactin 2 (ASTN2) as a candidate gene for attention-deficit/hyperactivity disorder (ADHD). ASTN2 plays a key role in glial-guided neuronal migration. To investigate whether common variants in ASTN2 contribute to ADHD disorder risk, we tested 63 SNPs spanning ASTN2 for association with ADHD and specific comorbid disorders in two samples: 171 families of children with ADHD and their parents (N = 592), and an adult sample comprising 604 adult ADHD cases and 974 controls. The C-allele of rs12376789 in ASTN2 nominally increased the risk for ADHD in the trio sample (p = 0.025). This was not observed in the adult case–control sample alone, but retained in the combined sample (nominal p = 0.030). Several other SNPs showed nominally significant association with comorbid disorders, especially anxiety disorder, in the childhood and adult ADHD samples. Some ASTN2 variants were nominally associated with personality traits in the adult ADHD sample and overlapped with risk alleles for comorbid disorders in childhood. None of the findings survived correction for multiple testing, thus, results do not support a major role of common variants in ASTN2 in the pathogenesis of ADHD, its comorbid disorders or ADHD associated personality traits.

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Acknowledgments

We thank all participating patients and controls for their support. This study was supported by the DFG (Grant RE1632/1-1, 1-3, 1-5 and RE1632/5-1 to AR, KFO 125 to AR, SW, CPJ, AW, TJ, MR and KPL; SFB TRR 58 to AR and KPL; RTG 1252, to AR and KPL), BMBF (01GV0605 to KPL), and the European Community’s Seventh Framework Programme (FP7/2007-2013), Grant Agreement no 602407 (FemNAT-CD; CMF, coordinator) and no 602805 (Aggressotype, AR). We are indebted to Andreas A. Ruppert, Genetics Research Center GmbH, Munich, Germany, for conducting genotyping of the samples. We thank J. Romanos, A. Boreatti-Hümmer, M. Heine and S. Gross-Lesch for their dedicated assistance in patient recruitment. T. Töpner, N. Steigerwald, G. Ortega, J. Auer, C. Gagel and N. Döring are credited for excellent technical assistance.

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Authors and Affiliations

  1. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Goethe University, Deutschordenstrasse 50, 60528, Frankfurt am Main, Germany

    Christine M. Freitag & Thomas Lempp

  2. Institute of Medical Biometry and Epidemiology, University of Marburg, Marburg, Germany

    T. Trang Nguyen

  3. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany

    Christian P. Jacob, Lena Weissflog & Andreas Reif

  4. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany

    Marcel Romanos, Tobias J. Renner, Susanne Walitza & Andreas Warnke

  5. Department of Child and Adolescent Psychiatry, University Hospital Tübingen, Tübingen, Germany

    Tobias J. Renner

  6. Department of Child and Adolescent Psychiatry and Psychotherapy, University of Zurich, Zurich, Switzerland

    Susanne Walitza

  7. Department of Psychiatry and Psychotherapy, University of Munich, Munich, Germany

    Dan Rujescu

  8. Department of Psychiatry and Psychotherapy, University of Halle, Halle, Germany

    Dan Rujescu

  9. Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany

    Klaus-Peter Lesch

  10. Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany

    Lena Weissflog & Andreas Reif

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  1. Christine M. Freitag
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  2. Thomas Lempp
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  3. T. Trang Nguyen
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  4. Christian P. Jacob
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Correspondence to Christine M. Freitag.

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Conflict of interest

P Jacob is a member of the advisory board “adult ADHD” of Medice and has received speaker’s fees by Medice. A. Reif has received funding by Astra Zeneca and Psynova. S. Walitza has received speaker’s fees by Janssen Cilag, AstraZeneca, Opopharma, and Eli Lilly.

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K.-P. Lesch and A. Reif share last authorship.

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Freitag, C.M., Lempp, T., Nguyen, T.T. et al. The role of ASTN2 variants in childhood and adult ADHD, comorbid disorders and associated personality traits. J Neural Transm 123, 849–858 (2016). https://doi.org/10.1007/s00702-016-1553-2

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