A population-specific HTR2B stop codon predisposes to severe impulsivity

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, Liliana Dell’Osso, Jaana Suvisaari, Emil Coccaro, Richard J. Rose, Leena Peltonen, Matti Virkkunen and David Goldman ()
Additional contact information
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
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
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
Matti Virkkunen: Institute of Clinical Medicine, University of Helsinki, Helsinki FI-00014, Finland
David Goldman: Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, Maryland 20852, USA

Nature, 2010, vol. 468, issue 7327, 1061-1066

Abstract: 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.

Date: 2010
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature09629 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:468:y:2010:i:7327:d:10.1038_nature09629

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature09629

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().