Health reports from direct-to-consumer genetic tests 'woefully incomplete'

Direct-to-consumer (DTC) genetic tests should not be used as a basis for medical decision making, according to two separate studies released last week.

The UK study was headed by Anneke Lucassen, Professor of Clinical Genetics at the University of Southampton and published in the British Medical Journal.  

'Genetic tests sold online and in shops should absolutely not be used to inform health decisions without further scrutiny,' she told The Guardian. 'Finding a "health risk" via these tests often does not mean a person will go on to develop the health problem in question, while "reassuring" results might be unreliable.'

The US study presented by Dr Edward Esplin at American Society of Human Genetics (ASHG) 2019 Annual Meeting in Houston, Texas, focused on three genes: MUTYH, associated with colorectal cancers, and BRCA1 and BRCA2, both associated with breast and ovarian cancers. Hundreds or thousands of variants in each of these genes can affect cancer risk, however, most DTC tests only look at a very small number of variants. 

FDA-approved DTC tests in the US cover only three BRCA variants, all of which are most common among people of Ashkenazi Jewish descent. Dr Esplin and his colleagues looked at the genomes of almost 120,000 patients who had been referred for clinical BRCA testing. Of the patients without Ashkenazi heritage, 94 percent had a mutation that would not have been detected, rising to 98 percent in those from Asian backgrounds and 99 percent in African-Americans.

Dr Esplin, who works for medical genetic testing company Invitae, refers to these missed variants as a 'clinical false-negative', adding that 'it could be the difference between preventing cancer and developing cancer.'

DTC company 23andme said that this is a 'false characterisation' as it makes clear that only certain variants are tested for, and that it does not claim to be a diagnostic test. 

Professor Lucassen's team estimate that a test for the three BRCA variants used by 23andme would miss around 80 percent of people in the UK with disease-causing BRCA variants.

Professor Lucassen explained her concern that receiving a negative result on a DTC test would likely be misinterpreted by some patients as an 'all clear':

'Most people who come to clinic ask: "Have I got the gene for breast cancer?" and imagine it's a single test, not that the test involves looking through around 20,000 letters of the genetic code to see if any one of them might be different.'

The BMJ paper also covers other aspects of DTC testing including polygenic risk scores, which are often misunderstood, not least by Health Secretary Matt Hancock earlier this year (see BioNews 992). His confusion illustrates the point these studies are making about how difficult it can be for non-specialists to correctly interpret genetic and genomic information, and to over- or underestimate their disease risk as a result.