A population-specific HTR2B stop codon predisposes to severe impulsivity

Bevilacqua, Laura, Doly, Stephane, Kaprio, Jaakko, Yuan, Qiaoping, Tikkanen, Roope, Paunio, Tiina, Zhou, Zhifeng, Wedenoja, Juho, Maroteaux, Luc, Diaz, Silvina, Belmer, Arnauld, Hodgkinson, Colin A., Dell’Osso, Liliana, Suvisaari, Jaana, Coccaro, Emil, Rose, Richard J., Peltonen, Leena, Virkkunen, Matti, & Goldman, David (2010) A population-specific HTR2B stop codon predisposes to severe impulsivity. Nature, 468(7327), pp. 1061-1066.

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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.

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ID Code: 75301
Item Type: Journal Article
Refereed: Yes
Keywords: Impulsivity, 5-HT2B, Human, mice, loss of function polymorphism
DOI: 10.1038/nature09629
ISSN: 1476-4687
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400) > Genetics not elsewhere classified (060499)
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 19 Aug 2014 22:16
Last Modified: 21 Aug 2014 01:51

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