Publication Date:
2010-12-24
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183507/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183507/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bevilacqua, Laura -- Doly, Stephane -- Kaprio, Jaakko -- Yuan, Qiaoping -- Tikkanen, Roope -- Paunio, Tiina -- Zhou, Zhifeng -- Wedenoja, Juho -- Maroteaux, Luc -- Diaz, Silvina -- Belmer, Arnaud -- Hodgkinson, Colin A -- Dell'osso, Liliana -- Suvisaari, Jaana -- Coccaro, Emil -- Rose, Richard J -- Peltonen, Leena -- Virkkunen, Matti -- Goldman, David -- AA-09203/AA/NIAAA NIH HHS/ -- AA-12502/AA/NIAAA NIH HHS/ -- Z01 AA000301-09/Intramural NIH HHS/ -- Z01 AA000301-10/Intramural NIH HHS/ -- Z99 AA999999/Intramural NIH HHS/ -- England -- Nature. 2010 Dec 23;468(7327):1061-6. doi: 10.1038/nature09629.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, Maryland 20852, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21179162" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Brain/metabolism
;
Case-Control Studies
;
Cell Line
;
Female
;
Finland
;
Founder Effect
;
Gene Expression Regulation
;
Gene Knockout Techniques
;
Genotype
;
Humans
;
Impulsive Behavior/*genetics
;
Male
;
Mental Disorders/genetics
;
Mice
;
Mice, 129 Strain
;
Mice, Knockout
;
Pedigree
;
Polymorphism, Single Nucleotide/genetics
;
Receptor, Serotonin, 5-HT2B/*genetics/*metabolism
;
Testosterone/blood/cerebrospinal fluid
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
