Just thinking you have poor endurance genes changes your body

If you want to win a race or stick to a difficult diet, coaches of all kinds will tell you it’s all about “mind over matter.” But that advice rarely crosses over into the medical community, where an inborn ability—or risk—is thought to depend more on genes and environment than on mindset. Now, in a study examining what may be a novel form of the placebo response, psychologists have found that just telling a person they have a high or low genetic risk for certain physical traits can influence how their body functions when exercising or eating, regardless of what genetic variant they actually have.

The results could be an eye-opener for medical providers and consumer DNA testing companies. “From a psychological science perspective, it’s not terribly surprising that genetic risk information can function this way,” says behavioral researcher Susan Persky of the National Human Genome Research Institute in Bethesda, Maryland, who was not involved in the study. But it’s a novel idea in the genetics community, she adds.

After getting ethics approval to conduct an experiment that involved deceiving participants, graduate student Bradley Turnwald and co-workers in the lab of psychologist Alia Crum at Stanford University in Palo Alto, California, recruited 116 young and middle-aged people for what they called a “personalized medicine study.” They tested each for a gene variant that influences a person’s capacity for exercise. The volunteers also took a treadmill test.

A week later, the participants were given a result, based not on their actual data, but rather on one of two groups into which they had been randomly placed. Some were told they had the form of a gene called CREB1 that makes a person tire easily; others were told they had the high-endurance version. Then they ran on the treadmill again.

This time, those who had been told they had the low-endurance version of CREB1 did worse on the test, even if they had the other variant. Compared with their results on the first test, on average their bodies removed toxic carbon dioxide less efficiently, their lung capacity dropped, and they stopped running 22 seconds sooner, the team reports today in Nature Human Behavior. And those who thought they had the high-endurance form of the CREB1 gene ran slightly longer on average before feeling hot and tired, regardless of what gene variant they had. “Simply giving people this information changed their physiology,” Turnwald says.

The team also tested a second group of 107 people for its version of FTO, a gene that influences how full we feel after eating. Some versions can also predispose people to obesity. Participants ate a small meal and rated their fullness. After being told, at random, that they had a version of FTO that made them hungrier than average or one that made them easily sated, participants ate the same meal. Those told they had the “hungry” version of the gene didn’t feel any different. But those who were told they had the other version felt less hungry on average after eating; they also had higher blood levels of a hormone that indicates a feeling of fullness.

In the cases of both genes, some of the changes in bodily reactions were larger than what the researchers measured between people who actually carried different versions of the genes, suggesting their attitude could change their risk as much or more than their genetics. “What people haven’t fully appreciated is that that information also puts you into a mindset: ‘I’m at high risk or I'm protected,’” Crum says. “And that alone can have potent effects on physiology and motivation.”

Such a placebo response to genetic information could have serious implications for genetic testing, especially commercially available products that can reveal risk scores for conditions such as Alzheimer’s disease and cancer. The Stanford team says people shouldn’t necessarily stop getting tested. But they—along with medical providers and genetic counselors—should keep in mind that just knowing about risk can subtly influence outcomes. The results suggest that if a person just thinks they are at high risk for, say, obesity, it could change their physiology in a way that makes them more prone to the condition, Turnwald says.

The next question is whether these effects fade quickly, or last for years.