A population-specific HTR2B stop codon predisposes to severe impulsivity.

Article Details


Bevilacqua L, Doly S, Kaprio J, Yuan Q, Tikkanen R, Paunio T, Zhou Z, Wedenoja J, Maroteaux L, Diaz S, Belmer A, Hodgkinson CA, Dell'osso L, Suvisaari J, Coccaro E, Rose RJ, Peltonen L, Virkkunen M, Goldman D

A population-specific HTR2B stop codon predisposes to severe impulsivity.

Nature. 2010 Dec 23;468(7327):1061-6. doi: 10.1038/nature09629.

PubMed ID
21179162 [ View in PubMed

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.

DrugBank Data that Cites this Article

NameUniProt ID
D(1A) dopamine receptorP21728Details
5-hydroxytryptamine receptor 2BP41595Details
Sodium-dependent dopamine transporterQ01959Details
D(2) dopamine receptorP14416Details
Amine oxidase [flavin-containing] AP21397Details
5-hydroxytryptamine receptor 3BO95264Details