The 0.01 per cent: can over-the-counter genetic tests help you be healthier?

I am 99.9 per cent the same as every single human on the planet.

By that definition, I’m nothing special. But the remaining 0.01 per cent makes me as unique and special as my mother told me I am.

That 0.01 per cent is just a few thousand switched A, T, C or Gs in the 3 billion ‘letter’ code that is my human genome.

These variations – called single nucleotide polymorphism or SNPs – are tiny inherited chemical changes in your DNA – and they can make all the difference. Some alter your appearance, while others can affect your chances of developing diseases, like cancer.

Scientists have been hunting for these cancer-related differences in our DNA for the past few decades. And the more of them we find, the more accurate a picture we build up about how cancer risk is linked to our genes.

Over the years, there have been some important findings. Recently, for example, our scientists found seven genetic changes that affect the risk of prostate cancer. And just a couple of years ago, around 80 more were linked to breast, prostate and ovarian cancers – and we continue to find more still.

There are also other variants linked to things like our smoking behaviour or how our body responds to exercise, that could also, indirectly, affect a person’s chances of diseases like cancer later in life.

In fact, researchers have discovered hundreds of gene variations that seem to affect cancer risk, either directly or indirectly. Theoretically, looking at a person’s DNA could reveal how likely they are to get cancer and so has the potential to help them change their behaviour to minimise their risk.

Although your DNA is no guarantee of cancer or any disease, that doesn’t stop companies from trying to sell tests that claim to predict your future.

To find out if these tests could show anything more useful than a horoscope, I volunteered to take an over-the-counter test, made by a US company called 23andMe… and this is what happened.

Prep

“Why do you want to do this?” asked Anna Middleton, a genetic counsellor from the Wellcome Trust Sanger Institute. “Other than for the article,” she added.

People get their DNA tested for many reasons, such as family planning, or to take preventative health measures – but I was just curious.

Anna asked me a few more questions about the small print of the test’s ‘Terms of Service’, which I hadn’t then read. But I made a mental note to myself to actually read them – after all, this wasn’t like downloading a new version of iTunes.

Then she asked something that took me by surprise.

“Well have you talked to your parents?”

I hadn’t.

“I mean, say you did find out you’re at risk for Alzheimer’s disease, how do you think your parents would feel about that? If you have it, then both or either could have passed it on to you and would also have an increased risk. Are they worried about that? How do you feel about telling them about that?”

She brought up a good point. My DNA is their DNA, and very similar to my brother’s.

After asking my family if they wanted to know the test results, they all agreed that they wanted to know the good, bad and the ugly.

But not everyone wants to know. For some, knowledge might not be power but rather a constant source of stress.

Can any good come from knowing you’re at risk of something you can do little to prevent , or may never happen? Or does it just cause people to worry for no reason?

On one hand, there’s evidence that knowing might not actually cause stress.

For example, a study from 2010 randomly assigned 162 people who had parents with Alzheimer’s to find out if they had the genetic markers for the disease or not. Results showed that there were no differences in anxiety or test-related distress between the groups who found out their risk, and those who didn’t. The researchers concluded that there was no “significant short-term psychological risks”.

And for some, the knowledge can actually give peace of mind, especially when it comes to stigmatised conditions such as obesity. There is also evidence that even with cardiovascular diseases there can be a sense of relief.

Dr Susanne Meisel, Cancer Research UK-funded research psychologist at Kings College London, explains: “Knowing one’s genetic make-up seems to provide an ‘explanation’ for their condition, even if the actual genetic risk is very small.”

But many experts feel that these tests are an unnecessary burden, a murky stain on an otherwise clean bill of health. Others argue that the studies that claim predictive genetic testing causes “no harm” are poorly designed, and have serious limitations, which could be skewing the results. And now some evidence is beginning to show that there might be long-term consequences to knowing your genetic risk for certain diseases – such as depression.

But I was still curious, so – having spoken to Anna – I forged ahead with the test.

The test

The test – which involves spitting into a test tube – arrived on an unassuming Tuesday and, heeding science journalist Ed Yong’s words after his experience, I decided not to do it at work. Instead, I took the tube home and – ironically – found myself spitting into it while both a repairman and my flatmate awkwardly watched.

But before the spitting starts, you need to register your kit and fill out some consent forms. I decided to actually read the terms of service, which mostly seemed to be legal jargon to protect 23andMe, such as:

• “We do not provide medical advice.”
• “The Services are not intended to be used by you for any diagnostic purpose and are not a substitute for professional medical advice.”

But embedded in the extensive legal document were a couple of things that caused me to sit up and pay attention.

For example, halfway through reading I came across this:

Also, at the time I took the test, none of the tests had been licensed – neither by the US’s Food and Drug Administration (FDA), nor the European Medicines Authority – this was pretty much ‘recreational genetics’.*

But what truly struck me was this: “Genetic Information you share with others could be used against your interests.”

This essentially refers to insurance companies’ ability to discriminate against you, based on your test results .

In the UK, there is no legislation preventing insurance companies or employers from discriminating on the basis of genetic differences. There is, however, a voluntary moratorium between the government and the insurance industry limiting access to genetic results – but it ends in 2019.

And while very few companies ask for genetic test results, as genetic testing becomes more commonplace requesting the results could become standard, and it could have negative consequences.

The document ended in ‘shouty’ capitals saying it didn’t make any promises about the services, just in case I still hadn’t got the message.

Despite all this, I signed the consent form, spat in the tube and posted my kit back to the company. Eight weeks later an email told me my results were ready.

But it still took me three days to build up the courage to look at them.

https://youtu.be/h1NY87i0AYo

• To see what the results section looks like watch this video

Results

The 23andMe website breaks down your results into four categories:

1. Traits – physical traits like eye colour or if you’re likely to be lactose intolerant.
2. Inherited conditions – conditions, like cystic fibrosis, that you can pass on to your children if your partner also a carrier.
3. Drug response – how gene variants are linked to how you react to different medicines.
4. Genetic risk factors – genetic variants that predict how likely you are to get a certain disease in the future, such as breast cancer.

Within the categories, all the things they test for are laid out in a list with a star rating next to it, indicating how robust the evidence is that a genetic variant is a good indicator of what it’s linked to.

You can expand and read more about the SNP they tested, and the different studies they used to validate it. There is also a section that helps you understand what your results mean.

For the genetic risk factors there’s an added step where you need to ‘unlock’ some of the results, so you’re actively choosing to find out your genetic risk – and the site provides advice on what to do with your results and a link to a genetic counselling.

On the whole everything is well communicated and quite clear. My results, thankfully, showed that I was pretty average. The only area where I deviated from the norm was how I respond to certain types of medicine.

But how good a risk predictor is it? Also do these results really make a difference?

Answer Sheet

“Most SNPs for disease are only very weakly associated,” says Cancer Research UK’s Professor Doug Easton, who – as well as helping identify hundreds of cancer linked SNPs – also helped track down the notorious BRCA1 gene in the 1990s.

While a combination of SNPs is better at predicting disease risk, 23andMe usually only looks at one or two variants for each disease they test for. That means that, for most people who take the test and show a variation, the risk of them getting that disease is only somewhat above or below the population average.

“SNPs are only a small percentage of the difference in a given trait, and only explain a proportion of the genetic risk of disease,” adds Prof Easton, explaining that there are many other risk factors that need to be taken into account. For example, family history, which could point to an inherited genetic fault in genes like BRCA1 or BRCA2 (which increases a persons risk of getting breast cancer by up to 90 per cent) or the person’s overall health and lifestyle.

And this point becomes obvious after I speak with Sir David Spiegelhalter, Winton Professor for the Public Understanding of Risk in the Statistical Laboratory at University of Cambridge, who took the 23andMe test back when they tested for diabetes, which was removed to appease the FDA.

“They told me, amongst other information, that I had an increased risk of diabetes,” he said. “They said that 31 out of 100 European men who share my genotype would develop Type 2 diabetes between 20 and 79, compared to an average of 26 out of 100.”

In other words, the test’s ability to predict what will actually happen to someone – and thus their practical usefulness – isn’t that great.

“Of course I have already lived to 62 without getting diabetes,” Speigelhalter points out.

Variation vs mutation

As well as looking at SNPs – which are variations in the letters that make up genes, the 23andMe test also looks at certain gene mutations – letters are missing from, or added to a gene. For example, it tests for certain mutations in the BRCA1 and BRCA2 genes, which cause the gene to stop working properly.

So are any of these mutations better predictors of risk? Not necessarily.

Prof Easton explains: “These mutations are special, in that they are quite common in Ashkenazi Jews. And in that population, a test for these mutations makes some sense. But in other populations, including the UK, that would be a poor test. If there are reasons to test BRCA1 and BRCA2, you’d need to do an analysis of the entire gene, not just one or two spelling mistakes.”

There are hundreds of different mutations in BRCA1 and BRCA2, and to look at all of those you would need to get the full DNA sequence – which means looking at all the letters not just the ones that might be switched. At the moment such sequencing is hugely complex and very expensive – so 23andMe doesn’t offer this.

So if you’re of Ashkenazi Jewish descent this test is useful to you. But if you’re of any other ethnic background this test tells you next to nothing.

And herein lies a problem. Many 23andMe’s variants are often only for certain populations – most often those of European backgrounds. But these tests are advertised to help people make healthier choices and “plan for the future”, which is pretty hard to do if the results don’t apply to you.

Make a change

But even if the results are relevant to you personally does anyone actually change their behaviour?

“The crucial issue is whether these risk numbers are useful – relevant to your current situation, and different enough from average to be interesting in their own right, or to motivate changes in behavior,” argues Spiegelhalter.

One would assume that, if you found out that you were at increased risk of developing cancer, you would change your behaviour to try and reduce that risk. Maybe you would quit smoking, drink less, eat more healthily or start exercising more but that doesn’t seem to be the case.

“Unfortunately, studies have shown that although people intend to change their behaviour, they don’t actually change it,” says Dr Meisel. She highlighted a 2010 analysis by the Cochrane Collaboration that combined the results of 20 different studies on genetic risk, and found no evidence that knowing about genetic risk affected a person’s behaviour.

But Dr Meisel suggests that it’s not all bad. “On the other hand, people don’t become more reckless when they know their genetic risk, or lack of risk, for a condition,” she says.

So where does that leave us?

Advice

If you’re thinking about having your genes tested for curiosity’s sake go for it. These tests can be interesting, just like a Buzzfeed quiz can be interesting.

But if you’re taking the test for health planning purposes, or to see if you’re at an increased risk of cancer, you need to be aware of the shortcomings. For example, if you belong to any ethnic minority group, many of the results of this test are a waste of money, because most of the results won’t apply to you.

On top of this, most of the things you can actually do about your results – giving up smoking, eating healthily, cutting down on alcohol and all the rest are just sensible things to do for anyone, regardless of their genes.

And – most important of all – genetics isn’t a guaranteed indication of your risk, but rather a small piece of the big picture that is your overall health. Rather than spending a hundred quid on a test, our advice is: if you’re worried about your health, your GP is a better bet. There are also excellent genetic counselling services that can help people in families that have a higher risk of developing cancer.

As for my final take away: there may be science behind 23andMe’s test – but I reckon I might as well have read my horoscope.

– Misha

* Since writing this some of the tests have been approved by the FDA