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A population-specific HTR2B stop codon predisposes to severe impulsivity

Author

Listed:
  • Laura Bevilacqua

    (Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, Maryland 20852, USA)

  • Stéphane Doly

    (INSERM UMR-S 839 and Université Pierre et Marie Curie, Institut du Fer à Moulin, Paris 75654, France)

  • Jaakko Kaprio

    (University of Helsinki
    Institute for Molecular Medicine, Helsinki FI-00014, Finland
    Unit for Child and Adolescent Psychiatry, National Institute for Health and Welfare, Helsinki FI-00271, Finland)

  • Qiaoping Yuan

    (Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, Maryland 20852, USA)

  • Roope Tikkanen

    (Institute of Clinical Medicine, University of Helsinki, Helsinki FI-00014, Finland)

  • Tiina Paunio

    (Helsinki University Central Hospital, Helsinki FI-00014, Finland)

  • Zhifeng Zhou

    (Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, Maryland 20852, USA)

  • Juho Wedenoja

    (University of Helsinki, Helsinki FI-00014, Finland
    Institute for Molecular Medicine Finland FIMM, University of Helsinki and National Institute for Health and Welfare, Helsinki FI-00014, Finland)

  • Luc Maroteaux

    (INSERM UMR-S 839 and Université Pierre et Marie Curie, Institut du Fer à Moulin, Paris 75654, France)

  • Silvina Diaz

    (INSERM UMR-S 839 and Université Pierre et Marie Curie, Institut du Fer à Moulin, Paris 75654, France)

  • Arnaud Belmer

    (INSERM UMR-S 839 and Université Pierre et Marie Curie, Institut du Fer à Moulin, Paris 75654, France)

  • Colin A. Hodgkinson

    (Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, Maryland 20852, USA)

  • Liliana Dell’Osso

    (University of Pisa, Pisa 56100, Italy)

  • Jaana Suvisaari

    (Helsinki University Central Hospital, Helsinki FI-00014, Finland)

  • Emil Coccaro

    (The Pritzker School of Medicine, University of Chicago)

  • Richard J. Rose

    (Indiana University)

  • Leena Peltonen
  • Matti Virkkunen

    (Institute of Clinical Medicine, University of Helsinki, Helsinki FI-00014, Finland
    Kellokoski Psychiatric Hospital, Kellokoski FI-04500, Finland)

  • David Goldman

    (Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, Maryland 20852, USA)

Abstract

Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency > 1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity.

Suggested Citation

  • Laura Bevilacqua & Stéphane Doly & Jaakko Kaprio & Qiaoping Yuan & Roope Tikkanen & Tiina Paunio & Zhifeng Zhou & Juho Wedenoja & Luc Maroteaux & Silvina Diaz & Arnaud Belmer & Colin A. Hodgkinson & L, 2010. "A population-specific HTR2B stop codon predisposes to severe impulsivity," Nature, Nature, vol. 468(7327), pages 1061-1066, December.
    • Handle: RePEc:nat:nature:v:468:y:2010:i:7327:d:10.1038_nature09629
    DOI: 10.1038/nature09629
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