Large Study Identifies Genetic Variants Linked to Risk Tolerance and Risky Behaviors

Based on genetic information from more than 1 million people
of European ancestry, results suggest the neurochemicals glutamate and GABA,
but not dopamine or serotonin, contribute to risk tolerance

An international group that includes researchers at
University of California San Diego School of Medicine has identified 124
genetic variants associated with a person’s willingness to take risks, as
reported in a study published January 14 in Nature Genetics.

The researchers emphasize that no variant on its own
meaningfully affects a particular person’s risk tolerance or penchant for
making risky decisions — such as drinking, smoking, speeding — and non-genetic
factors matter more for risk tolerance than genetic factors. The study shows
evidence of shared genetic influences across both an overall measure of risk
tolerance and many specific risky behaviors.

The genetic variants identified in the study open a new
avenue of research on the biological mechanisms that influence a person’s
willingness to take risks.

“Being willing to take risks is essential to success in the
modern world,” said study co-author Abraham Palmer, PhD, professor of
psychiatry and vice chair for basic research at UC San Diego School of
Medicine. “But we also know that taking too many risks, or not giving enough
weight to the consequences of risky decisions, confers vulnerability to
smoking, alcoholism and other forms of drug addiction.”

The genetic variants identified in this study open a new
avenue of research on the biological mechanisms that influence a person’s
willingness to take risks. Photo courtesy of Pixabay

Palmer’s lab, which includes co-author Sandra Sanchez-Roige,
PhD, is working to understand the genetic basis of individual differences in
impulsive and risky decision-making styles. They want to understand the
fundamental molecular and cellular processes that shape human behavior, and
learn how to prevent and treat drug abuse.

“Risk-taking is thought to play a role in many psychiatric
disorders,” said co-author Murray Stein, MD, MPH, Distinguished Professor of in
the departments of Psychiatry and Family Medicine and Public Health, and
vice-chair for clinical research in psychiatry at UC San Diego School of
Medicine.

“For example, patients with anxiety disorders may perceive
increased risk in certain situations and therefore avoid them unnecessarily.
Understanding the genetic basis for risk tolerance is critical to understanding
these disorders and developing better treatments.”

The team measured participants’ overall risk tolerance based
on self-reports. They found that genetic variants associated with overall risk
tolerance tend to also be associated with more risky behaviors, such as
speeding, drinking, tobacco and cannabis consumption, and with riskier
investments and sexual behaviors. They also found shared genetic influences on
overall risk tolerance and several personality traits and neuropsychiatric
traits, including ADHD, bipolar disorder, and schizophrenia.

The effects of each of the 124 genetic variants on an
individual basis are all very small, but the researchers found their combined
impact can be significant.

“The most important variant explains only 0.02 percent of
the variation in overall risk tolerance across individuals,” said senior author
Jonathan Beauchamp, PhD, assistant professor of economics at the University of
Toronto. “However, the variants’ effects can be combined to account for greater
variation in risk tolerance.”

The researchers created a polygenic score, which captures
the combined effects of 1 million genetic variants and statistically accounts
for approximately 1.6 percent of the variation in general risk tolerance across
individuals. They say the score could be used to study how genetic factors
interact with environmental variables to affect risk tolerance and risky
behaviors, but they caution that the score cannot meaningfully predict a
particular person’s risk tolerance or risk taking behavior.

The 124 genetic variants associated with risk tolerance are
located in 99 separate regions of the genome. The study found no evidence to
support previously reported associations between risk tolerance and genes
related to the neurochemicals dopamine or serotonin, which are involved in the
processing of rewards and mood regulation.

Instead, the findings suggest that the neurochemicals
glutamate and GABA contribute to variation in risk tolerance across
individuals. Both are important regulators of brain activity in humans and
animals — glutamate is the most abundant neurotransmitter in the body and
boosts communication between neurons, whereas GABA inhibits it.

“Our results point to the role of specific brain regions —
notably the prefrontal cortex, basal ganglia and midbrain — that have
previously been identified in neuroscientific studies on decision-making,”
Beauchamp said. “They conform with the expectation that variation in risk
tolerance is influenced by thousands, if not millions, of genetic variants.”

The data for this study were from the UK Biobank, the
personal genomics company 23andMe, and 10 other, smaller genetic datasets.

The study was led by 96 researchers in the Social Science
Genetic Association Consortium, which investigates the influence of genetics on
human behavior, well-being and social science-related outcomes through
large-scale studies of human genomes.

The study was funded, in part, by the National Institutes of
Health, Ragnar Söderberg Foundation, Swedish Research
Council, Jan Wallander and Tom Hedelius Foundation, ERC, Pershing Square Fund
of the Foundations of Human Behavior, Open Philanthropy Project, Government of
Canada through Genome Canada and the Ontario Genomics Institute, Social
Sciences and Humanities Research Council of Canada, Frontiers of Innovation
Scholars Program, and Interdisciplinary Research Fellowship in
NeuroAIDS.

This article has been republished from materials provided by
University of California
San Diego School of Medicine. Note: material may have been edited for
length and content. For further information, please contact the cited source. 

Reference
Linnér, R. K., Biroli, P., Kong, E., Meddens, S. F. W., Wedow, R., Fontana, M. A., ... & Nivard, M. G. (2019). Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences. Nature Genetics, 1.