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Bipolar disorder risk alleles in children with ADHD

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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Abstract

Bipolar disorder (BD) and attention deficit/hyperactivity disorder (ADHD) may share common genetic risk factors as indicated by the high co-morbidity of BD and ADHD, their phenotypic overlap especially in pediatric populations, the high heritability of both disorders, and the co-occurrence in families. We therefore examined whether known polygenic BD risk alleles are associated with ADHD. We chose the eight best SNPs of the recent genome-wide association study (GWAS) of BD patients of German ancestry and the nine SNPs from international GWAS meeting a ‘genome-wide significance’ level of α = 5 × 10−8. A GWAS was performed in 495 ADHD children and 1,300 population-based controls using HumanHap550v3 and Human660 W-Quadv1 BeadArrays. We found no significant association of childhood ADHD with single BD risk alleles surviving adjustment for multiple testing. Yet, risk alleles for BD and ADHD were directionally consistent at eight of nine loci with the strongest support for three SNPs in or near NCAN, BRE, and LMAN2L. The polygene analysis for the BP risk alleles at all 14 loci indicated a higher probability of being a BD risk allele carrier in the ADHD cases as compared to the controls. At a moderate power to detect association with ADHD, if true effects were close to estimates from GWAS for BD, our results suggest that the possible contribution of BD risk variants to childhood ADHD risk is considerably lower than for BD. Yet, our findings should encourage researchers to search for common genetic risk factors in BD and childhood ADHD in future studies.

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Acknowledgments

The authors express their gratitude to the patients and their families for participation. The German Ministry for Education and Research (National Genome Research Net plus 01GS0820) and the German Research Foundation (DFG; KFO 125/1-1, SCHA 542/10-2, ME 1923/5-1, ME 1923/5-3, HE 1446/9-1) supported this study. These institutions had no further role in study design, collection, analysis and interpretation of data, writing of the report, and the decision to submit the paper for publication.

Conflict of interest

The authors declare that they have no conflict of interest relevant to this work.

Author information

Authors and Affiliations

  1. University Hospital of Child and Adolescent Psychiatry, University of Bern, Bolligenstr. 111, 3000, Bern 60, Switzerland

    B. G. Schimmelmann & M. Dauvermann

  2. Department of Child and Adolescent Psychiatry, Universitätsklinikum Essen, University of Duisburg-Essen, Essen, Germany

    A. Hinney, Ö. Albayrak, M. Dauvermann & J. Hebebrand

  3. Institute for Medical Informatics, Biometry and Epidemiology, Universitätsklinikum Essen, University of Duisburg-Essen, Essen, Germany

    A. Scherag, C. Pütter, S. Pechlivanis & K.-H. Jöckel

  4. Institute of Neuroscience and Medicine (INM-1), Structural and Functional Organization of the Brain, Genomic Imaging, Research Center Juelich, Juelich, Germany

    S. Cichon

  5. Institute of Human Genetics, University of Bonn, Bonn, Germany

    S. Cichon

  6. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany

    S. Cichon

  7. Heinz Nixdorf Recall Study Group, Essen, Germany

    K.-H. Jöckel

  8. Popgen Study Group; Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    S. Schreiber

  9. KORA Study Group; Institute of Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany

    H. E. Wichmann

  10. Department of Child and Adolescent Psychiatry, Technical University of Aachen, Aachen, Germany

    K. Konrad, C. Wilhelm & B. Herpertz-Dahlmann

  11. Department of Child and Adolescent Psychiatry, University of Cologne, Cologne, Germany

    G. Lehmkuhl & J. Sinzig

  12. Department for Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinik Bonn, Bonn, Germany

    J. Sinzig

  13. Department of Child and Adolescent Psychiatry, Julius-Maximilians-University Wuerzburg, Wuerzburg, Germany

    T. J. Renner, M. Romanos & A. Warnke

  14. Department of Child and Adolescent Psychiatry, University Munich, Munich, Germany

    M. Romanos

  15. Department of Psychiatry and Psychotherapy, Julius-Maximilians-University Würzburg, Würzburg, Germany

    K. P. Lesch & A. Reif

Authors
  1. B. G. Schimmelmann
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  2. A. Hinney
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  3. A. Scherag
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  4. C. Pütter
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  5. S. Pechlivanis
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  6. S. Cichon
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  7. K.-H. Jöckel
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  8. S. Schreiber
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  9. H. E. Wichmann
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  10. Ö. Albayrak
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  11. M. Dauvermann
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  12. K. Konrad
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  13. C. Wilhelm
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  14. B. Herpertz-Dahlmann
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  15. G. Lehmkuhl
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  16. J. Sinzig
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  17. T. J. Renner
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  18. M. Romanos
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  19. A. Warnke
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  20. K. P. Lesch
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  21. A. Reif
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  22. J. Hebebrand
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Corresponding author

Correspondence to B. G. Schimmelmann.

Additional information

B. G. Schimmelmann and A. Hinney denote co-first authorship.

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Schimmelmann, B.G., Hinney, A., Scherag, A. et al. Bipolar disorder risk alleles in children with ADHD. J Neural Transm 120, 1611–1617 (2013). https://doi.org/10.1007/s00702-013-1035-8

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  • DOI: https://doi.org/10.1007/s00702-013-1035-8

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