Taking an online DNA test to find out your ancestry is one thing, but be careful about using them to assess your genetic predisposition to disease.

Key points:

  • SNP chips are “extremely unreliable” in detecting rare genetic variants, new research shows
  • The technology is popular online, often used by consumers who want to trace their family history
  • The number of direct-to-consumer genetic testing-related referrals to clinical genetics services has increased

New research shows the technology widely used in direct-to-consumer genetic tests is more likely to be wrong than right at detecting rare disease-causing genetic variations.

University of Exeter researchers launched the study after learning of cases where women had surgery scheduled after wrongly being told they had very rare genetic variations in the gene BRCA1.

Women who carry a fault in the BRCA1 or BRCA2 gene have a high lifetime risk of breast cancer, estimated to be in the range of 30-60 per cent, and a lifetime ovarian cancer risk of about 20 per cent.

These genetic variations are very rare, with about 0.25 per cent of the population carrying the mutated BRCA1 or BRCA2 genes.

The University of Exeter’s research, recently published in the British Medical Journal, involved a large-scale analysis of the technology using data from nearly 50,000 people.

They found that SNP chips, technology widely used by commercial genetic testing companies, were “extremely unreliable” in detecting rare variants.

According to the research, very rare, disease-causing variants detected using a SNP chip were “more likely to be wrong than right”, with 84 per cent of tests returning false positives.

Peter MacCallum Cancer Centre clinical geneticist Paul James wasn’t surprised by the study’s conclusion.

“They’re confirming something that we’ve been aware of through clinical experience,” he said.

SNP ‘not really the right tool for the job’

SNP chips are used in research for genome-wide association studies.

The technology is popular online, often used by consumers who want to trace their family history.

Technology commonly found in direct-to-consumer online tests uses genotyping, which doesn’t work if you’re looking for something rare.(

ABC News: James Carmody


Stuart MacGregor, head of the statistical genetics lab at QIMR Berghofer, said although the direct-to-consumer online tests were an “exciting opportunity” for someone to trace their family heritage, the technology simply wasn’t designed to scan for rare variants.

“It’s not really the right tool for the job,” Professor MacGregor said.

“They usually have reasonable accuracy for things like eye colour and other fun traits, but for medical applications, for rare variants for things like BRCA mutations, they’re not fit for that purpose.”

Dr James said SNP chips weren’t able to detect rare variants very well because they effectively scanned the genetic material, whereas proper medical genetic testing reads it thoroughly.

When looking for rare genetic variants in a clinical setting, Dr James said experts would sequence all the genes which had been implicated in those cancers, looking at every single point of the gene for anything unusual that would be a potential abnormality or gene mutation.

He explained that the technology used in direct-to-consumer online tests used a form of “sampling”.

“Because the way the technology works, it’s not reading it in a nice, simple way from start to finish, it’s actually doing something called genotyping,” Dr James said.

“If you’re looking for something rare, genotyping doesn’t work.”

‘A trend that’s happening more and more’

Monash University public health genomics program head Paul Lacaze said issues had started to arise because Australians were taking genetic information provided to them through direct-to-consumer tests and inputting them into third party websites in an attempt to determine if they had rare disease-causing genetic variations.

Dr Lacaze said this often led to “misleading results” because the websites effectively “guessed” someone’s risk factor.

“Then the lab will look at that and then try to validate the result and more often than not, they can’t,” he said.

Last year, Dr Lacaze collaborated on a study investigating the impact of direct-to-consumer genetic testing on Australian clinical genetics services.

Researchers surveyed Australian clinical genetics services about the number of direct-to-consumer genetic testing-related referrals they’d received over the past 10 years, finding 11 publicly funded services had reported over 100 of them.

Dr Lacaze said although the raw figure “wasn’t massive”, it was becoming an increasing problem as internet-based tools became more popular in Australia.

In Australia, genetic testing is only offered through a family cancer clinic, and people who have a family history and meet certain qualifications can get reimbursed testing.

People who are at high risk are “very likely” to qualify and the added benefit of going to a family cancer clinic is also having genetic counsellors on site, Dr James said.

“If people are concerned about rare genetic conditions then they really need to talk to the experts, rather than just fishing around online for these kinds of tests which are not going to help them,” he said.

Dr James said through his work at the Peter MacCallum Cancer Centre, he’d seen an increase in the number of direct-to-consumer genetic testing-related referrals, but it wasn’t a “big problem”.

“It certainly does happen,” he said.

Few options for those ‘curious’

For people who are curious about their genetic predisposition — who have no family history — there isn’t a pathway through the public health system.

And Dr Lacaze estimates that approaching a private testing clinic for this kind of testing could cost up to $1,200.

People who didn’t have that kind of money would “find other ways” to satisfy their curiosity, he said, which was why so many Australians were turning to the internet to find this information.

Dr Lacaze is advocating for less restrictive criteria for genetic testing in Australia, to make high-quality testing more accessible for the broader population.

He’s looking to launch a pilot study of 10,000 adult volunteers in Australia, offering preventative genetic screening.