Title: Identifying genes responsible for a highly heritable aspect of antisocial behavior in 7 year-old children
Name: Robert Plomin
Year: 2004
Type: Research Grant
Summary: Our recent work on the genetic basis of antisocial behavior has concentrated on defining the most heritable antisocial behavior phenotype for molecular genetic analyses. We have now repeatedly demonstrated that while antisocial behavior with co-occurring psychopathic traits is highly heritable, antisocial behavior without psychopathic traits is not (Viding, Blair, Moffitt, & Plomin, 2005; Viding, Jones, Frick, Moffitt, & Plomin, 2006). In addition, multivariate twin model-fitting work has demonstrated considerable genetic overlap between antisocial behavior and psychopathic traits (Viding, Frick, & Plomin, in press). This essential twin analysis work has been instrumental in validating appropriate targets for molecular genetic analyses.

Based on our repeated finding of the high heritability of psychopathic antisocial behavior, as well as our multivariate results, the following approaches are being taken with our molecular genetic analyses.

1) Using the TEDS sample, we have replicated recent findings of association between a particular genotype (COMT) and antisocial behavior in children with high levels of hyperactivity (Thapar et al., 2005). This association did not hold for psychopathic traits, indicating that COMT may be a candidate gene for impulsive, rather than premeditated type of antisocial behavior. These findings are currently being prepared for publication.
2) Our DNA pooling study is ongoing. Given the costs associated with such study, we wanted to perform additional twin analyses in order to optimize the sample selection. Based on the findings from our twin analysis, we are now conducting a DNA pooling study on individuals with high levels of BOTH antisocial behavior and callous-unemotional traits. We also wanted to wait for the development of more powerful Affymetrix SNP microarray (GeneChip), which we discovered was in the pipeline soon after we received the Guggenheim funding. The new Affymetrix GeneChip can be used to genotype 500,000 DNA markers (SNPs), which is sufficient to scan the entire genome. We have continued to develop our use of pooled DNA genotyped on GeneChips (Butcher et al., in press; Meaburn et al., 2005, 2006), which we use to screen the 500,000 SNPs and then follow up on nominated SNPs with individual genotyping. Given the extra costs of the new GeneChip, we have also obtained additional money to supplement the funds provided by the Guggenheim Foundation.

Bibliography: Butcher, L. M., Schalkwyk, L., & Plomin, R. "Applicability of DNA pools on 500K SNP microarrays for cost-effective initial screens in genomewide association studies." Nucleic Acids Research. (In press.)

Meaburn, E., Butcher, L. M., Schalkwyk, L. C., & Plomin, R. "Genotyping pooled DNA using 100K SNP microarrays: A step towards genomewide association scans." Nucleic Acids Research 34 (2006): e27.

Thapar A., Langley K., Fowler T., Rice F., Turic D., Whittinger N., Aggleton J., Van den Bree M., Owen M., O'Donovan M. "Catechol O-methyltransferase gene variant and birth weight predict early-onset antisocial behavior in children with attention-deficit/hyperactivity disorder." Arch Gen Psychiatry 62(11) (Nov. 2005): 1275-8.

Viding, E., Blair, R. J. R., Moffitt, T. E., & Plomin, R. "Evidence for substantial genetic risk for psychopathy in 7-year-olds." Journal of Child Psychology and Psychiatry 6 (2005): 592-597.

Viding, E., Frick, P., & Plomin, R. "Genetic contribution to psychopathic personality traits in children." In Biology of Personality and Individual Differences, edited by T. Canli. (In press.)

Viding, E., Jones, A., Frick, P., Moffitt, T., Plomin, R. "Heritability of antisocial behaviour at nine: Do callous-unemotional traits matter?" Developmental Science. Under review, 2006.