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It is game over for 23andMe, and rightly so

The market for personal genome services is facing a reality check. While the most prominent and innovative company 23andMe has flourished so far, in the past few years many of its competitors have gone…

This may not remain on shelves in stores or online. brendanlim

The market for personal genome services is facing a reality check. While the most prominent and innovative company 23andMe has flourished so far, in the past few years many of its competitors have gone out of business. Now, with the latest warning from the US Food and Drug Administration (FDA), the rest of the genome testing industry may be counting its days too. 23andMe has failed to provide scientific evidence for their genetic tests and the FDA has urged them in a public letter to halt the marketing of their services until further notice.

The FDA treats genetic testing as a “medical device”, and it wants all such devices to meet high quality standards. In this the FDA is right. 23andMe provides information that may lead its users to self-medicate, which, if based on faulty information can lead to serious adverse effects. The FDA does not mind if people would like to know what their DNA sequence is, but it is concerned about the interpretation of that data by 23andMe.

The FDA’s letter is unlikely to have surprised the people at 23andMe. They acknowledge similar concerns in their Terms of Service. They are also aware of the limited predictive ability of their tests for common diseases. 23andMe follows scientific progress in genetic risk prediction research closely, and by now they must have realised that the promise of personal genome services has faded.

In 2009, when the company first filed for marketing authorisation of their service, the future of genetic prediction looked very bright. The discovery of genetic markers for common diseases had just started to take off. Each issue of Nature Genetics, the top journal for scientific discoveries in genetics and genomics, reported new markers for different diseases. It seemed global collaborations would soon rapidly unravel the genetic origins of disease.

But the reality appeared more complex.

Genomics researchers caught the bigger fish first, as new markers had increasingly smaller effects on disease risk. By now, only four years later, many scientific studies have investigated the predictive ability of risk models similar to those on which 23andMe’s tests are based. Their results have been mostly discouraging, even though researchers have never used that word. Genetic markers are generally unable to predict risk of common diseases, and adding more markers to risk models does not improve their predictive ability that much.

The results of these studies are no surprise: most of them have investigated risk predictions that are based on relatively few genetic markers. For instance, 23andMe uses only 15 markers to predict the risk of coronary heart disease, 11 for type-2 diabetes, two for melanoma and obesity, and one for esophageal and stomach cancer. These numbers are much lower than the dozens that have already been discovered. Predictive ability can be good only if markers have a lot of impact on disease risk, such as in age-related macular degeneration and several autoimmune diseases.

Champions of the genetic medicine revolution could have been warned by looking at the degree of “heritability” of diseases. The lower this percentage, the less predictive the test can become. 23andMe discloses these estimates:

Heritability of melanoma is estimated at around 20%; type-2 diabetes at 26%; colorectal, esophageal and stomach cancer all around 30%; coronary heart disease between 39% and 56%; and type-1 diabetes between 72% and 88%.

But what does this mean? The high heritability of type-1 diabetes means that genes play a dominant role in causing the disease. If scientists manage to unravel all genetic markers for type-1 diabetes, a genetic test will be able to predict with high accuracy if a person will get diabetes.

Unfortunately, due to all the complex interactions between the markers, this full unravelling is impossible. The number of interactions is probably so high that every patient will have his or her own unique complex cause of disease. And what has never happened cannot be identified or predicted by big data.

Advances in genome science will improve what tests offer, but these improvements will be small. While the hope is based on big data, the reality is that most diseases are simply not genetic enough. Other risk factors such as diet, body weight, smoking, exercise and stress are too important. And big data cannot change the biology of diseases – it will not make them more genetic.

That is why genetic testing for common diseases will never become as predictive as champions of genetic testing hope.

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10 Comments sorted by

  1. Chris Booker

    Research scientist

    Sad, 23 and Me and the only ones left of the direct-to-consumer (DTC) gene sevices: deCODE was bought out by Amgen who shut down their consumer side, Navigenics was bought out by Life Sciences who shut down their DTC operation.

    Say what you will about overhyping genetic tests and problems with their interpretation, I think there is a good argument for public access and involvement. Of course, if 23andme were to disappear completely you could still get tests done by somewhere like the Genographic…

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    1. Matthew Berryman

      logged in via Facebook

      In reply to Chris Booker

      Chris, I think the sensible option is to consider how this information (and other information more generally on the Internet) needs to mediated by specialists, rather than specialists seen as the single source. You're not going to stop people from reading medical things on the Internet, but it's important that people seek experts, who are (one hopes) less prone to the types of logical errors that people can make in interpreting data (use of analogies, confusing correlation with causation, etc…

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    2. Ken Taylor

      Research Scientist at CSIRO

      In reply to Chris Booker

      I agree.

      The FDA and similar medical licencing bodies are invariably subject to regulatory capture http://en.wikipedia.org/wiki/Regulatory_capture . They introduce the "mechanisms in place which have kept science at arms length from the public". It's not that genetics is going away, it's the gatekeepers asserting control. Many people also prefer faith in a professional, who shields them from uncertainty. Knowledge and its limitations can keep you awake at night.

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  2. Matthew Berryman

    logged in via Facebook

    The complexity is not just about the interaction between markers, but in the full picture, encompassing methylation, chromatin, etc. and also importantly environmental factors. But does not knowing the whole story mean that we cannot describe the probabilities, and even put some confidence bounds on them? Obviously not. Thus 23andme is not necessarily a bad thing. A reading of the FDA's findings is about the quality of the research into those statistics, as well as the QA around the microarrays themselves…

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    1. Matthew Berryman

      logged in via Facebook

      In reply to Matthew Berryman

      Sorry, just to clarify on wording, I should have written "the software implementation of the statistical analysis also matters, even if the statistics are /correct on paper/ and presented well." Obviously if the software is wrong, they aren't calculated correctly.

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    2. Michael Vagg

      Clinical Senior Lecturer at Deakin University School of Medicine & Pain Specialist at Barwon Health

      In reply to Matthew Berryman

      Genetic counselling is a highly skilled area, and requires training in both genetic science and people skills. I hate to think of the confusion that false-positive or false-negative tests may cause, or even that true positive and negative results can cause if not carefully interpreted. The implications of genetic testing need to be carefully explained without hype beforehand, and results need to be individually interpreted, since as Prof Janssens explains above, it's not as reliable as hoped even if flawlessly conducted.

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    3. Matthew Berryman

      logged in via Facebook

      In reply to Michael Vagg

      Who genuinely hoped that it would be 100% definitive, though? There was hype along those lines when the HGP was "completed", but the papers didn't seem to carry that view. I concur with your views on counselling, I don't see that that necessarily rules out a place for services like 23andme, but it does mean that careful regulation needs to happen, and I welcome the FDA's decision (which reflects poorly on their business decisions, I guess, but that's almost another matter for another TC piece :)

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  3. Matthew Berryman

    logged in via Facebook

    Another issue of concern is that even if 23andme get things right, they still allow you to download your SNP data, which you can then on your own / using sites like https://promethease.com/ondemand generate your own analysis, with none of the safeguards provided by 23andme following FDA rules.

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  4. Laura Henze Russell

    logged in via Twitter

    The big picture is not that 23andMe is not precise enough in predicting risks of diseases. It is that genes are at best 50% of the equation: nature vs. nurture, genes vs. environment, exposures and events. It is helpful in showing defects in methylation and detoxification pathways, for example, which means one is more likely to get poisoned and have health impacts from toxins, which doctors do not usually raise as a consideration. They are all about the germs, and then maybe the genes, but we all…

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  5. Harry Banaharis

    logged in via LinkedIn

    "While the most prominent and innovative company 23andMe has flourished so far, in the past few years many of its competitors have gone out of business."

    Actually, 23andme has not been particularly innovative. And I'm unclear about what the author means by flourish as they have not actually turned a profit and are unlikely to in the near future based on their existing business model.

    Their business model, since 2008, has been to genotype their customers against a single nucleotide polymorphism…

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