Direct-to-consumer (DTC) genetic tests are advertised as a way to “find out what your DNA says”. Some promise insights into ancestry or disease risks, while others claim to provide information on personality, athletic ability, and child talent. People might be drawn to DTC genetic testing in the hope that it will provide clear cut information about their future health. But interpretation of genetic data is complex and context dependent and DTC genetic tests might report false positive and false negative results. A false positive result indicates that a person has a high genetic risk of a disease or condition when they actually don’t, while a false negative result indicates a person has a low genetic risk of a disease or condition when the person actually does have it.
These uncertainties may arise based on several aspects. A genetic test per se may simply deliver a wrong result for a given gene or a given locus within the genome. First, genetic tests from different sources are rarely compared (cross-validated) at a selection of gene loci for reproducible deliverance of identical test results. Second, the genotype of an individual does not all the time translate into the expected clinical phenotype of the patient. There may exist variations at the level of the molecular phenotype, there may exist an array of confounding factors, the patients may be a compound heterozygote, or the two alleles at the patients genetic locus may undergo transcriptional bursting, just to name a few. Lastly, while upon epidemiological analysis a correlation between a certain gene and the occurrence of a disease or the risk for a disease might exist in large patients populations, the same may not apply to every single patient individually.
Thus, the genome and its working are immensely complex. No wonder then that experts in the field of (pharma)genomics are warning that results found via third party interpretation services need particular care. This is because the “raw data” that such services interpret will contain errors, and because the databases used to interpret the data may not be up to date. When people receive a “bad news” result from a direct-to-consumer (DTC) genetic test, many may turn to their general practitioner (GP) for advice. However, most worrying in this context is an apparent significant gap in genomic literacy among medical doctors and other health care professionals. Indeed, only 1 in 10 physicians responding to a USA-based survey of 10’000 physicians reported feeling confident in their knowledge of (pharmaco)genomics and its clinical implications; less than 1 in 3 physicians had ever ordered a pharmacogenetic test, and only 1 in 8 physicians had recommended or ordered a test in the previous six months. This may even be more of a problem with direct to consumer (DTC) test concerned with personal or family history suggestive of a genetic condition, or test results concerning future health risks such as positive BRCA tests and the prospective risk of developing breast cancer.
In any case, receiving direct to consumer (DTC) genetic test results with seemingly positive or negative test result at a certain genetic locus of interest, which would led a patient, or even a healthy individual, to take action, should led healthy individuals, patients, and treating physicians to have i) the test results confirmed by a second, cross validated test in order to exclude experimental errors, and ii) have an true expert in (pharmaco)genetics and/or genetic counselling looking over and analysing the test results in order to circumvent inappropriate measures to be taken. The example of the American lady cited above should be enough of a warning for everyone involved. According experts are easily reachable both in the US and in Canada.
See here a short sequence on the problem we talk about here: