Gene variants associated with antisocial behaviour: A latent variable approach

Mary Jane Bentley, Haiqun Lin, Thomas V. Fernandez, Maria Lee, Carolyn M. Yrigollen, Andrew J. Pakstis, Liliya Katsovich, David L. Olds, Elena L. Grigorenko, James F. Leckman

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Objective The aim of this study was to determine if a latent variable approach might be useful in identifying shared variance across genetic risk alleles that is associated with antisocial behaviour at age 15 years. Methods Using a conventional latent variable approach, we derived an antisocial phenotype in 328 adolescents utilizing data from a 15-year follow-up of a randomized trial of a prenatal and infancy nurse-home visitation programme in Elmira, New York. We then investigated, via a novel latent variable approach, 450 informative genetic polymorphisms in 71 genes previously associated with antisocial behaviour, drug use, affiliative behaviours and stress response in 241 consenting individuals for whom DNA was available. Haplotype and Pathway analyses were also performed. Results Eight single-nucleotide polymorphisms (SNPs) from eight genes contributed to the latent genetic variable that in turn accounted for 16.0% of the variance within the latent antisocial phenotype. The number of risk alleles was linearly related to the latent antisocial variable scores. Haplotypes that included the putative risk alleles for all eight genes were also associated with higher latent antisocial variable scores. In addition, 33 SNPs from 63 of the remaining genes were also significant when added to the final model. Many of these genes interact on a molecular level, forming molecular networks. The results support a role for genes related to dopamine, norepinephrine, serotonin, glutamate, opioid and cholinergic signalling as well as stress response pathways in mediating susceptibility to antisocial behaviour. Conclusions This preliminary study supports use of relevant behavioural indicators and latent variable approaches to study the potential 'co-action' of gene variants associated with antisocial behaviour. It also underscores the cumulative relevance of common genetic variants for understanding the aetiology of complex behaviour. If replicated in future studies, this approach may allow the identification of a 'shared' variance across genetic risk alleles associated with complex neuropsychiatric dimensional phenotypes using relatively small numbers of well-characterized research participants.

Original languageEnglish (US)
Pages (from-to)1074-1085
Number of pages12
JournalJournal of Child Psychology and Psychiatry and Allied Disciplines
Volume54
Issue number10
DOIs
StatePublished - Oct 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Developmental and Educational Psychology
  • Psychiatry and Mental health

Keywords

  • Antisocial behaviour
  • co-action of gene variants
  • latent variable analysis
  • shared variance

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