Increased burden of rare protein-truncating variants in constrained, brain-specific and synaptic genes in extremely impulsively violent males with antisocial personality disorder

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00669806%3A_____%2F24%3A10477839" target="_blank" >RIV/00669806:_____/24:10477839 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/24:10477839 RIV/00216208:11140/24:10477839 RIV/00064165:_____/24:10477839

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Elj.bstGi6" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Elj.bstGi6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/gbb.12882" target="_blank" >10.1111/gbb.12882</a>

Result language

angličtina

Original language name

Increased burden of rare protein-truncating variants in constrained, brain-specific and synaptic genes in extremely impulsively violent males with antisocial personality disorder

Original language description

The genetic correlates of extreme impulsive violence are poorly understood, and there have been few studies that have characterized a large group of affected individuals both clinically and genetically. We performed whole exome sequencing (WES) in 290 males with the life-course-persistent, extremely impulsively violent form of antisocial personality disorder (APD) and analyzed the spectrum of rare protein-truncating variants (rPTVs). Comparisons were made with 314 male controls and publicly available genotype data. Functional annotation tools were used for biological interpretation. Participants were significantly more likely to harbor rPTVs in genes that are intolerant to loss-of-function variants (odds ratio [OR] 2.06; p &lt; 0.001), specifically expressed in brain (OR 2.80; p = 0.036) and enriched for those involved in neurotransmitter transport and synaptic processes. In 60 individuals (20%), we identified rPTVs that we classified as clinically relevant based on their clinical associations, biological function and gene expression patterns. Of these, 37 individuals harbored rPTVs in 23 genes that are associated with a monogenic neurological disorder, and 23 individuals harbored rPTVs in 20 genes reportedly intolerant to loss-of-function variants. The analysis presents evidence in support of a model where presence of either one or several private, functionally relevant mutations contribute significantly to individual risk of life-course-persistent APD and reveals multiple individuals who could be affected by clinically unrecognized neuropsychiatric Mendelian disease. Thus, Mendelian diseases and increased rPTV burden may represent important factors for the development of extremely impulsive violent life-course-persistent forms of APD irrespective of their clinical presentation.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Genes, Brain and Behavior

ISSN

1601-1848

e-ISSN

1601-183X

Volume of the periodical

23

Issue of the periodical within the volume

1

Country of publishing house

DK - DENMARK

Number of pages

24

Pages from-to

e12882

UT code for WoS article

001162908900001

EID of the result in the Scopus database

2-s2.0-85185133447