Tuesday, January 15, 2019 Tuesday, January 15, 2019

Considering Genetic Testing? Here Are Some Things to Think About

Have you had your genetics tested? If you have, you’re not alone, for interest in genetic testing has risen remarkably of late: In 2017, suppliers sold more to-consumer genetic testing kits than in all previous years combined.

People purchasing the tests probably felt that knowledge of their DNA could help them tailor their lifestyles to their genetic code, thereby optimizing their health and performance. (Dan spoke about this a little in an episode of humanOS Radio with Alon Keinan.) But does genetic testing actually help people feel and function better?

If you collate the results of relevant studies, it seems that receiving information about genetics scarcely affects the health decisions people make. And because some believe that their genetic blueprint strongly determines their lives’ trajectories, numerous studies have shown that many of us feel disempowered and distressed on learning our genetic dispositions to disease.

Until recently we knew nothing about an important question related to this though: What are the effects of an individual simply learning whether he or she has a beneficial or detrimental variant of a gene on the person’s subsequent physiology?

A team of scientists led by Alia Crum from Stanford University set out to answer this question, and their results are fascinating. The study design is a little complicated, but don’t get hung up on it because the findings and implications are most important.

Here’s what they did:

 

Study design

Alia’s team did two experiments – one on endurance exercise, one on appetite regulation. Fundamentally, the two experiments used the same steps:

  • First, each participant’s DNA was sequenced to identify whether the individual has the high-risk, moderate risk, or protective variant of the relevant gene*. So, these are three groups of actual genetic risk.
  • Next, the researchers assessed participants’ baseline biology and behavior:
    1. Exercise experiment: participants’ maximal endurance exercise performance, metabolic physiology, breathing, and perceptions of exercise were measured.
    2. Appetite experiment: participants consumed a standardized meal before measures of appetite hormones and feelings of satiety were taken.
  • Then it was time to inform people in each of the three actual genetic risk groups that they have either 1) the high-risk or 2) the protective variant of the relevant gene. So, these groups are of perceived genetic risk, and some people were deliberately deceived. The scientists delivered this information via a genetic test report comprising information taken from popular press and scientific publications about the effects of the gene variants. The report was much like one you’d receive from a consumer genetic testing lab.
  • A week after step two, participants repeated the tests done in step two. The researchers then compared the measures taken at the two visits.

Here’s what they found:

Experiment 1: Perceived genetic risk affects maximal endurance exercise

In the first experiment, people who were told they have the high-risk version of the gene stopped running 22 seconds earlier than they did at baseline. This information also impaired how well these people used oxygen to supply their muscles with energy** and hindered their breathing***. The reports given to participants explained that people with the high-risk variant of the gene feel hotter during exercise and, sure enough, the people told they carry this variant reported feeling hotter too.

Experiment 2: Perceived genetic risk affects satiety

In the second experiment, people who were told they have the protective version of the gene reported 40% higher satiety and had two-and-a-half times higher blood levels of a hormone that suppresses food intake****.


New research shows that perceptions of one's genetics has remarkable effects on exercise and appetite – something to consider if you get your genetics tested!
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Important points

First, please note that in both experiments these effects were seen regardless of whether the information they received was true.

Second, the study design allowed the scientists to work out whether actual genetic risk or perceived genetic risk had larger effects on the outcomes*****. And guess what… in several instances perceived genetic risk had stronger effects on the test results than actual genetic risk!

We don’t really understand why participants’ perceptions influenced their biology so much. The researchers speculate that the changes resulted from a shift in mindset, which has been shown to affect biology, attention, and motivation. I have to admit that I find this explanation a bit woolly. However, I don’t have a coherent alternative explanation, and my comment is no slight on these experiments – they were impressively well carried out.

 

Genetic testing: a handful of considerations for the future

These two experiments raise all sorts of questions.

One relates to this specific context: How would perceived genetic risk influence people over longer periods of time?

Another of course concerns companies providing to-consumer genetic tests. How can these companies optimize how they communicate information about genetic risk to maximize the likelihood of consumers experiencing beneficial effects on consumer health and health behaviours?

And this point doesn’t even consider the validity of consumer tests… are they accurate?

I should add that the absolute effects of variation in single genes on health outcomes is generally vanishingly small.

This is a crucial point that is often overlooked.

Yes, there are very rare instances in which genetic mutations have causal roles in diseases such as obesity. But it isn’t possible to use people’s genetic signatures to identify most individuals who develop obesity, and one of many reasons for this is that behaviors interact with genetics to determine susceptibility to diseases. This is in part why we focus so much on physical activity, sleep, and diet – things you have more control over – at humanOS.

Needless to say, genetic testing is just one way to assess predisposition to disease, so scientists will soon assess the effects of delivering information about other risk factors too, including lifestyle, family history, and alternative types of to-consumer tests you can purchase (blood chemistry tests, gut microbiome tests, epigenetic tests, and so on).

It would also be valuable to know how a person’s traits (which are stable) and states (which are more dynamic) affect how they respond to receiving such information. Perhaps individuals who are prone to anxiety would benefit from having their test results shared in a different way, for example.

 

Closing

For numerous reasons, I’ve been sat on the fence about genetic testing for a long time.

And I’m still sat on it.

While reading this paper hasn’t pulled me towards or pushed me away from recommending getting such tests done, ironically it has shifted my mindset a little. These experiments should remind us all that how we perceive information about our biology (such as our genetics) influences our health. By celebrating positive things that you know about yourself you might just nudge how you feel and function in the right direction. And if you take a genetic test and the report indicates that you have high-risk variants of certain genes, please realize that your genes aren’t your destiny, and in many instances their effects on your health and performance may be much smaller than the effects of your mindset!

 

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*In the exercise experiment, the genotypes of interest were the AA (high-risk) and GG (protective) variants of CREB1 rs2253206. People with the high-risk genotype typically have slightly lower endurance exercise capacity, higher core body temperature during endurance exercise, and respond less well to endurance exercise training.

In the appetite experiment, the genotypes of interest were the AA (high-risk) and TT (protective) variants of FTO rs9939609. People with the high-risk genotype are more likely to be obese and report lower satiety after meals, perhaps because of lower changes in appetite hormones.

**CO2:O2 exchange rate.

***The volume of gas the people inhaled and exhaled fell by over two litres per minute.

****GLP-1, a hormone produced by the intestines that reduces food intake by acting on receptors in the brain.

*****To calculate the effects of actual genetic risk, the researchers compared the baseline test results of people with the protective genotype to those with the high-risk genotype. To calculate the effects of perceived genetic risk, the scientists compared the results of each participant’s baseline test to his or her second test in each group of perceived genetic risk.

 

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