A new study, published in Nature Neuroscience, has analysed data from 1.5 million people to identify genes underlying behaviours related to self-regulation. As one of the largest genome-wide association studies ever conducted, the study has greatly developed our knowledge of antisocial behaviours and has the potential to influence future treatments.
Behaviours and disorders related to self-regulation, such as substance use and antisocial behaviours, have profound consequences not just for the affected individual and their family, but for society as a whole. Such impulse control-related behaviours are referred to as “externalising”, as they are manifested outwardly, unlike “internalising” disorders such as anxiety.
Identifying the genes associated with such behaviours is crucial to better understand these externalising disorders. In turn, safe and effective treatments could be developed. To do this, the current study carried out a genome-wide association study (GWAS) on 1.5 million people.
Phenotypes related to externalising disorders
The team used the GWAS data to study a group of phenotypes previously indicated to be related to externalising behaviours. These phenotypes included alcohol and drug use, number of sexual partners and tendency to take risks.
Genomic structural equation modelling (SEM) was then applied to the GWAS summary statistics to identify the variants associated with the above phenotypes.
Identifying genes associated with antisocial behaviours
In total, the researchers identified 579 single nucleotide polymorphisms (SNPs) associated with a tendency towards externalising behaviours. Overall, 121 of the identified SNPs have never been associated with self-regulation disorders before. In fact, 7% of the SNPs had never been reported as associated with any trait, let alone externalising traits.
Next, the team carried out bioinformatic analyses on the collected data. The results suggested that the identified associated genes affected early neurodevelopment. This then manifests as externalising behavioural patterns that can occur across an individual’s lifespan.
Interestingly, the team found that when the SNPs were looked at individually, each only had a small association with externalising behaviours. Single genes were found to only predispose an individual to externalising disorders, rather than having a deterministic effect. This opposes previous studies which have claimed that specific genes have very strong effects on antisocial behaviours and substance abuse.
“[This study] illustrates that genes don’t code for a particular disorder or outcome; there are no genes ‘for’ substance use disorder, or ‘for’ behaviour problems,” joint senior author Danielle Dick said. “Instead, genes influence the way our brains are wired, which can make us more at risk for certain outcomes. In this case, we find that there are genes that broadly influence self-control or impulsivity, and that this predisposition then confers risk for a variety of life outcomes.”
Polygenic risk scores
The researchers also calculated polygenic risk scores (PRSs) for externalising behaviours. PRSs are single value estimates of how likely an individual is to develop a certain trait or disease.
To generate these scores, the team used their GWAS data as well as each individual’s electronic health record. The scores created were associated with a wide range of diseases, such as HIV infection and liver cirrhosis. However, these scores also correlated with a variety of social factors, such as educational levels and unemployment. These results highlight the influence of both genetic and social factors in an individual’s tendency to develop externalising disorders.
Conclusions and future work
The 579 genes associated with externalising behaviours identified in this study have provided brand new insights into our understanding of behaviours relating to self-regulation. In addition, the team’s PRS for externalising disorders has one of the largest effect sizes (a measure of prediction power) of any polygenic score in psychiatric and behavioural genetics.
The researchers hope that their findings contribute to further work exploring how biological and social risks influence externalising disorders. In addition, they have created a live website of study FAQs that will be updated in response to feedback from the scholarly community, journalists and the general public.