Learning One’s Genetic Risk Might Affect Eating and Exercise
Thinking about genetic risk could trigger placebo and nocebo effects.
Posted Jan 25, 2019
Digging into your DNA is easier (and more popular) than ever. By late 2017, it was estimated that approximately 1 in 25 American adults had accessed their personal genetic information, most often through commercial companies like 23andMe or Ancestry.com.
Some are researching family origins. But the rise of precision medicine — and a growing understanding of genetic risk for thousands of medical conditions — mean that many consumers use genetic testing to learn their propensity for certain diseases and disorders. Learning genetic risk information can affect people psychologically: Past research has found that receiving such information can trigger emotional and behavioral changes. Now, a new study suggests that learning about genetic risk may have the power to influence someone’s physiology, too — even if what they’re told isn’t entirely accurate.
The research, published last month in Nature Human Behavior, comprises two studies in which participants were randomly assigned to learn either that their genes put them at high risk for certain traits that are associated with obesity, or that their low-risk genes were “protective” against the same traits. Researchers conducted genotype testing at the start of each study; some participants were told correct information, while others were assigned to receive information that didn’t reflect their actual risk.
The first experiment centered on the CREB1 gene, the high-risk form of which has been linked to poorer aerobic exercise capacity, increased body temperature during exercise, and fewer cardiovascular improvements observed when working out. At the beginning of the study, participants ran on a treadmill to get baseline measures of their cardiorespiratory physiology, their running endurance (how long they could run before giving up), and their subjective perception of the task (how hard or easy running was, how hot they felt, and when they started to feel tired).
They returned a week later to complete the treadmill test again. This time, they were told beforehand either that they had the high-risk form of the CREB1 gene, or that they had the protective form. Regardless of what their genotypes actually were, those who were told they were at high risk reported feeling more worried and less in control of their exercise capacity and, during the second treadmill task, stopped running significantly earlier than they had the first time. They also demonstrated statistically significant physiological changes that signaled decreased exercise capacity, such as a lower maximum capacity for CO₂:O₂ gas exchange.
Those who were randomly assigned to learn they had the protective gene, meanwhile, saw no physiological changes compared to the first session, but were able to run significantly longer before reporting that the exercise felt hard, or that they felt hot.
The subjective changes observed in the protective group could be seen as a placebo effect, says Brad Turnwald, lead author of the study and a doctoral student at Stanford University. Meanwhile, the physiological changes observed in the high-risk group may be what’s known as a nocebo effect, which happens when learning about possible negative outcomes makes them more likely to occur. “Many people think of placebo and nocebo effects in terms of taking a medication,” Turnwald says. “But information itself can lead to these effects, not only in people’s subjective experience, but also in their physiology.”
To test if the outcomes were unique to CREB-1, or if they would extend to other paradigms, the authors conducted a second study centered on the FTO gene, one of the best-studied genetic risk factors for obesity. The high-risk form of FTO is associated with lower self-reported and physiological satiety, meaning people with this genotype report feeling full more slowly than others and show lower levels of glucagon-like peptide 1 (GLP-1), a gut peptide that signals satiety to the brain.
In the second study, participants consumed a 480-calorie meal after fasting overnight and reported how full they felt at various points before and after eating. Levels of GLP-1 in their blood were measured at each timepoint.
Participants returned to redo the task and consume an identical meal a week later, but this time, were told before eating that they had the high-risk or the protective form of FTO. Participants who were told they had the protective genotype reported a 1.4-fold increase in how full they felt after eating relative to their baseline session. They also experienced a 2.5-fold increase in levels of GLP-1. “This time, people who learned that they had ‘better’ genes experienced the boost,” Turnwald explains, in another potential placebo effect. Those who were told they were at high risk didn’t change significantly on those measures, but reported feeling more worried and perceived themselves as having less control over how full they would feel.
Both studies taken together demonstrate the power of mindset, Turnwald says, especially because on some of the measures, thinking one had a certain genotype had a more powerful physiological or behavioral effect than actually having that genotype.
“Mindset matters,” agrees Catharine Wang, who studies community health at Boston University and was not involved in the study. “This study reminds us to think about how some types of genetic information might lead to unintended consequences. If we give genetic risk information on [certain] traits, it’s easy to see how a self-fulfilling prophecy would kick in.”
Wang notes that much of the past research on genetic risk information, including several studies she’s conducted, focused on the risk for an overall disease or condition — such as obesity — as opposed to the risk for specific traits, like exercise capacity or satiety. Such specificity could have had an impact on the observed effects. “Not all genetic risk is viewed equally,” she says. “Depending on the framing, some risk information [could be] more motivating than others.” While she views the study as well-designed, she cautions that the relatively small sample sizes (each study had slightly more than 100 participants) should be taken into account when assessing the strength of the results.
The authors’ decision to present low-risk genes as “protective” could be a useful framework for companies and clinicians tasked with sharing genetic risk information, Wang says. “My sense is that they would have seen different outcomes had they not framed low risk as protective. But these results do suggest that if we start presenting ‘protective’ genetic information, it could have beneficial outcomes.”
Obesity-related traits were selected for ethical reasons, Turnwald says; the authors wanted to study something that would matter to participants, but hoped to avoid more charged kinds of genetic risk, like that of Alzheimer’s disease or cancer. He emphasizes that the physiological and behavioral changes seen for these genes don’t necessarily extrapolate to others — especially those implicated in more serious conditions. “Our results don’t speak to cancer, for instance,” he says.
Because the researchers wanted to minimize as much as possible the time that participants spent believing potentially false information, they ensured that each was fully debriefed before leaving the site, Turnwald says. But that prevented them from examining long-term outcomes, as participants only spent about an hour pondering their supposed genetic risk before researchers filled them in on the study’s design and purpose (and their real genetic risk, if they still wanted to know).
“What we hypothesize could happen [over the long term], based on other work on mindset and placebo effects, is that there is a potential for these effects to grow and fester over time,” he says. He points to the exercise framework as a possible example: “If I learn that my capacity to exercise is lower, for instance, it may become easier for me to recall times in which I got tired faster than other people,” he notes. “The next time I exercise, it may feel more difficult, which may lead me to quit my exercise sooner or worry that there’s no point in exercising anyway.”
The takeaway from the study isn’t that people shouldn’t learn their genetic risk, Turnwald stresses. Future research should focus on how genetic risk can be most effectively presented, both to those who are at high risk and those who are at low risk. He adds, “It would be great if we could harness the beneficial effects we saw while trying to mitigate the negative effects.”
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