These genes influence whether you take risks

Tech Science 24. jun 2019 3 min Research Assistant, PhD student Pascal Nordgren Timshel Written by Kristian Sjøgren

New research has discovered hundreds of genetic variants that are involved in determining whether you are prone to taking risks or playing it safe.

People’s willingness to take risks varies enormously.

Some of us live on the edge or in the fast lane; others prefer the safe and familiar. The difference applies to both adventurousness and the general tendency to take risks but also to the propensity to engage in specific types of risky behaviour such as smoking, drinking alcohol, number of sexual partners and driving faster than the speed limit.

We are different.

A large genome-wide association study of more than 1 million people has identified hundreds of genetic variants that determine why you tend to take more risks than your neighbour or vice versa.

Not surprisingly, the research shows that these genetic variants especially affect one specific part of the body.

“We discovered that the genes affecting people’s propensity to take risks are especially active in certain areas of the brain involved in making decisions and the brain’s reward system by influencing the neurotransmitters glutamate and gamma-aminobutyric acid (GABA). The interesting thing about these transmitters is that they have opposing effects on the communication between our neurons. GABA inhibits the nerve signals and glutamate stimulates them. Our results suggest that the communication between the neurons plays an important role in people’s tendency to take risks,” explains the Danish participant in the study, PhD student Pascal Nordgren Timshel, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

The new research results have been published in Nature Genetics.

Previously suspected biological pathways do not influence risk-taking

The researchers examined the factors that influence whether people are prone to taking risks.

The researchers thought initially that many biological systems and pathways would influence people’s risk-taking . Specifically, the researchers focused on five main biological pathways: the steroid hormone cortisol, the neurotransmitters dopamine and serotonin and the sex hormones testosterone and estrogen.

Nevertheless, the researchers found no evidence of any association between risk-taking and the genes influencing the secretion of these neurotransmitters or hormones. They examined the genomes of the participants more broadly and found an association with the genes involved in neurotransmission with glutamate and GABA.

“Previous analysis was based on genetic information from a few hundred to one thousand people, and researchers specifically examined a few individual genes that were suspected of influencing risk-taking. Our study, in contrast, was not limited to specific genes but instead examined all genes in a study population of almost 1 million people,” says Pascal Nordgren Timshel.

99 genetic variants associated with general propensity to take risks

In this bioinformatic study, the researchers manipulated very large data sets that link studies of the participants’ whole genome with information about their self-reported propensity to take risks in general, self-reported adventurousness, smoking habits, alcohol consumption, number of sex partners and penchant for speeding.

The researchers could thus detect genetic variants that appear to increase risk-taking. These genetic variants arise when one or a few of the components of DNA are replaced by others. This slightly changes the function of the gene in which the DNA is located, and if the gene is involved in regulating the release of glutamate or GABA, then these genetic variants may affect risk-taking.

The researchers found several hundred genetic variants that increase people’s tendency to take specific risks – including smoking or drinking alcohol – and 99 genetic variants that specifically increase people’s general propensity to take risks.

The vast majority of these genes are associated with releasing GABA and glutamate in the brain.

“Our analysis indicates which areas of the brain specifically influence whether people are prone to take risks. We found, for example, that the genes that affect the propensity to take risks are especially active in specific areas of the prefrontal cortex, the area of the brain that regulates personality and decision-making. However, one problem in this study is that it had limited anatomical detail. The prefrontal cortex is a general designation, but we would like to be more specific,” says Pascal Nordgren Timshel.

Understanding risk-taking and disease at the cellular level

Pascal Nordgren Timshel is working to improve understanding of how individual cells in the prefrontal cortex function to increase people’s genetic tendency to take risks.

During his research project, he plans to use genetic analysis and bioinformatics to define the identity and function of cells more precisely.

This will improve the understanding of exactly what happens when people take risks and of how brain diseases and metabolic disorders develop.

“The long-term dream is to be able to apply my bioinformatic methods to a molecular atlas of all human cell types to understand the biology of disease at the smallest level: the cell. In fact, realizing this dream is not that far away,” says Pascal Nordgren Timshel.

Pascal Nordgren Timshel is participating in the research project Human Cell Atlas, which aims to map all the thousands of types of cells in the human body.

“The human body comprises many different types of cells, and we know amazingly little about the diversity of these cells. Understanding the molecular mechanisms by which diseases develop requires mapping the identity and function of the cells involved. The Human Cell Atlas is the dawn of a new era in understanding cells that will become crucial for all aspects of biology and medicine.”

Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences” has been published in Nature Genetics. Several of the authors are employed at the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

My research as a computational biologist focuses on developing data-driven algorithms and data integration to harness the power of large-scale genomic...

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