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Learning About Genetic Risk Could Affect Individuals' Physiology

NEW YORK (GenomeWeb) – Just learning their genetic risk for disease could alter people's physiological states, according to a new study.

Psychological research has found that people's mindsets can influence their health. The placebo effect, for instance, suggests that if people think something is helpful, then their response to it could meet that expectation. Learning genetic information, Stanford University researchers said, could then influence people's mindsets and even their physiology or subjective experiences.

Stanford's Alia Crum and her colleagues conducted a pair of experiments in which they determined participants' genetic risk of obesity, but instead randomly assigned them to be told they were at high or low risk. Just being told they were at higher risk influenced the participants' performance on measures of exercise ability or satiety, regardless of their actual genetic risk, as they reported today in Nature Human Behaviour.

"[T]he present results show that receiving genetic risk information can change gene-relevant outcomes, which is important to consider as the reach of personalized genetic testing increases exponentially," the researchers wrote in their paper.

Teasing out the effect of perceived genetic risk from the effect of actual genetic risk can be tricky, they noted. Here, they conducted genetic testing of individuals to gauge whether they had high, medium, or low risk of disease, but then randomly assigned half of each of those groups to be told they had high or low disease risk, even if they did not. The participants also underwent testing to ascertain how learning this genetic risk information affected their physiology.

The researchers argued this deception was necessary. They added that they tried to minimize its potentially negative effects by focusing on learning genetic risk of obesity — rather than, for instance, learning risk of developing cancer or Alzheimer's disease, which they said would be more emotionally charged — and limited the time that the participant held this incorrect belief to an hour during which they were under clinical supervision. After that, the participants were thoroughly debriefed.

For their first experiment, the researchers examined the effect of learning CREB1 rs2253206 status in a cohort of 116 people. This genotype is associated with poorer aerobic exercise capacity, increased body temperature during exercise, and less cardiac improvement from exercise.

As the researchers expected, participants' perceived genetic risk influenced their cardiorespiratory physiology. People who were told they had the high-risk genotype performed more poorly on measures of CO2:O2 gas exchange, ventilatory flow rate, and how long they ran before giving up, as compared to their own baseline taken a few weeks earlier.

For some of these measures, the effect of perceived genetic risk was greater than that of participants' actual genetic risk, the researchers reported.

The researchers likewise examined the effect of learning FTO rs9939609 status, a risk factor for obesity, on physiology measures of and self-reported satiety. Again, they found that perceived genetic risk changed both physiological satiety, as measured by the glucagon-like peptide 1 response, and self-reported fullness after eating. The effect size of perceived genetic risk on self-reported satiety was higher than that associated with their actual FTO genotype, the researchers added.

These findings indicate that learning genetic risk can affect individuals' health, the researchers said.

"Clinicians, genetic counselors, and direct-to-consumer testing organizations should thus be mindful that the mere act of delivering genetic information can influence actual risk," they wrote.

They added that more research is needed into determining when genetic risk disclosure is appropriate and how to best make those disclosures.