Hundreds of Genes Associated with Risk Tolerance and Risky Behaviour Identified in Study of Over One Million People
Dr. James MacKillop, Director of St. Joseph’s Healthcare Hamilton’s Peter Boris Centre for Addictions Research, was a part of an international team that identified 124 genetic variants associated with an individual’s willingness to take risks in a sample of over one million participants. The findings of this large-scale study were published in the journal Nature Genetics.
The 124 genetic variants are found in 99 different regions of the genome. Researchers found no evidence to support previously reported associations between risk tolerance and certain genes, such as genes that affect dopamine or serotonin (which are involved in the processing of rewards and mood regulation).
According to researchers, a single genetic variant on its own will have no meaningful impact on a person’s risk tolerance or likelihood of engaging in risky behaviour. However, when taken collectively, the genetic variants identified in the study illustrate some of the biological mechanisms that influence an individual’s willingness to take risks.
“Genetic variants that are associated with overall risk tolerance — a measure based on self-reports about individuals’ tendencies to take risks in general — tend to also be associated with more speeding, drinking, tobacco and cannabis consumption, and with riskier investments and sexual behavior,” said Jonathan Beauchamp, corresponding author and Assistant Professor of Economics at the University of Toronto.
As part of the study, researchers created a ‘polygenic score’ to capture the combined effects of 1 million genetic variants. The score statistically accounts for less than 2 percent of the variation in general risk tolerance across individuals.
“The score can be used to study how genetic factors interact with environmental variables to affect risk tolerance and risky behaviours,” said Beauchamp, who expects the score to be useful in social science studies.
“A fascinating aspect of these findings is the evidence that the genetic correlates of risk tolerance were shared with psychiatric symptoms, such as attention deficit hyperactivity disorder and bipolar disorder,” commented MacKillop, adding “this demonstrates the common biological basis for both normal variation in risk orientation and clinically disordered behaviour.”
Whether these findings will ultimately contribute to improvements in prevention or treatment is an open question.
“On one hand, the polygenic score could ultimately be useful in identifying individuals who have a greater innate vulnerability for conditions associated with risky behavior,” noted MacKillop, “but, on the other, the score only predicts a small proportion of a person’s risk orientation.”
“What is clear,” he added, “is that once you aggregate data to very large sample sizes, the genetic associations come into very sharp relief.”
The results indicate that glutamate and GABA, which are important regulators of brain activity, contribute to variation in risk tolerance across individuals. Glutamate is the most abundant neurotransmitter in the body, boosting communication between neurons, while GABA works in an opposite fashion to inhibit communication.
The study demonstrated the role of specific regions of the brain, particularly the prefrontal cortex, basal ganglia, and midbrain. These areas have been previously identified in scientific studies on decision-making.
Researchers also noted that the results conform to the expectation that variation in risk tolerance is influenced by thousands of genetic variants instead of a small subset of genes. In other words, there is no single gene that determines risky behaviour.
According to MacKillop, these studies demonstrate the importance of international collaboration. By leveraging numerous datasets from researchers all over the world, these studies gain a statistical advantage to reliably detect genetic influences on psychological traits.
In addition to directing the Peter Boris Centre, MacKillop is the Peter Boris Chair in Addictions Research at St. Joe’s, Director of the Michael G. DeGroote Centre for Medicinal Cannabis Research, and Professor of Psychiatry and Behavioural Neurosciences at McMaster University.
Data from the study were from the UK Biobank, the personal genomics company 23andMe, and several other, smaller genetic datasets.
This research was funded by several international groups, including the Government of Canada through Genome Canada and the Ontario Genomics Institute, and the Social Sciences and Humanities Research Council of Canada.