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Antisocial Behavior May Be Highly Polygenic

NEW YORK (GenomeWeb) – Antisocial behavior may be highly polygenic, according to a new meta-analysis of genome-wide association studies.

Previous studies have indicated that about half the variance in antisocial behavior can be traced to genetic factors. So far, however, no genetic variants have been linked to such behavior, which can run the gamut from aggression to deceitfulness and from theft to violent felonies.

Researchers from the Broad Antisocial Behavior Consortium analyzed genome-wide association data collected from five large population-based cohorts and three target cohorts to search for genetic regions linked to antisocial behavior. As they reported today in JAMA Psychiatry, the consortium researchers uncovered three loci linked to antisocial behavior when they stratified the cohorts by sex.

"Our meta-analyses of diverse continuous measures of [antisocial behavior] found that ASB is heritable and highly polygenic and suggests that part of the genetic architecture is sex specific," the authors wrote in their paper.

The researchers, led by Vrije Universiteit Amsterdam's Danielle Posthuma, gathered data from five cohorts, consisting of a total 16,400 people, as their discovery cohort. The cohorts had undergone genome-wide genotyping on commercially available arrays and imputation to the 1000 Genomes reference panel. Overall, they examined more than 7 million SNPs. The studies relied on a range of measures of antisocial behavior, from teacher report forms to conduct disorder scale measures.

While the researchers did not find any variants of genome-wide significance linked to antisocial behavior in the full cohort, they did find such variants when they conducted the analysis using samples from just men and just women. The female-only meta-analysis uncovered two loci — one on chromosome 1 and one on chromosome 11 — associated with antisocial behavior. Meanwhile, the male-only meta-analysis found a signal on the X chromosome.

The researchers developed a polygenic risk score for antisocial behavior that they tested in three target cohorts, one from the case-control Finnish Crime Study, one from the Michigan State University Twin Registry, and another from Yale-Penn study. The Broad ABC antisocial genetic risk scores were linked to the case or control status of members of the Finnish Crime Study cohort, the researchers reported.

In all three cohorts, there was a stronger effect by sex, suggesting that there are be sex differences in the genetic architecture of antisocial behavior. However, Posthuma and her colleagues noted that the effect sizes were small and that they thus had limited prognostic abilities.

Using their samples, the researchers also estimated that all SNPs explain about 5.2 percent of the phenotypic variance seen in antisocial behavior. At the same time, they also noted that there was a negative genetic association between antisocial behavior and educational attainment and a positive genetic correlation with neuroticism — a finding they said was in line with previous twin studies.

As Posthuma and her colleagues pointed out, their study is limited by a lack of gold standard for determining antisocial behavior and its inclusion of adult and pediatric samples, among other factors.

"Still, we found a polygenic signal, and our correlation analyses further reflect the validity and usefulness of our approach," they added in their paper. "To identify individual SNPs or genes associated with ASB, we found that even larger samples are needed."