SUCKERS: Up to 40 percent of DNA results from consumer genetic tests might be bogus

There is increasing demand from the public for direct-to-consumer (DTC) genetic tests, and the US Food and Drug Administration limits the type of health-related claims DTC tests can market. Some DTC companies provide raw genotyping data to customers if requested, and these raw data may include variants occurring in genes recommended by the American College of Medical Genetics and Genomics to be reported as incidental/secondary findings. The purpose of this study was to review the outcome of requests for clinical confirmation of DTC results that were received by our laboratory and to analyze variant classification concordance.


We identified 49 patient samples received for further testing that had previously identified genetic variants reported in DTC raw data. For each case identified, information pertaining to the outcome of clinical confirmation testing as well as classification of the DTC variant was collected and analyzed.


Our analyses indicated that 40% of variants in a variety of genes reported in DTC raw data were false positives. In addition, some variants designated with the “increased risk” classification in DTC raw data or by a third-party interpretation service were classified as benign at Ambry Genetics as well as several other clinical laboratories, and are noted to be common variants in publicly available population frequency databases.


Our results demonstrate the importance of confirming DTC raw data variants in a clinical laboratory that is well versed in both complex variant detection and classification.


Direct-to-consumer (DTC) genetic tests are advertised and sold directly to the public and offer information that may include ancestry, risks of developing certain conditions, carrier status for autosomal recessive diseases, predicted drug response, and nondisease phenotypic traits such as eye color. Owing to a growing interest in human genetics and personalized health care, there has been an increased demand for this type of testing from the public. There is a growing market for DTC genetic testing, with numerous companies (e.g., Family Tree DNA, My Heritage, 23andMe, currently offering products to the public. DTC tests can provide genetic information to individuals who might otherwise never have been tested due to circumstances such as lack of a family history of disease, inaccessibility of clinical genetic testing, prohibitive cost, or poor insurance coverage. However, unlike clinical genetic tests, DTC tests are not diagnostic and offer risk information for only a limited set of conditions.

In the United States, the Food and Drug Administration (FDA) restricts DTC genetic testing companies from offering products that function as diagnostic tests.1 In April 2017, the FDA authorized one DTC company, 23andMe, to market genetic health risk tests for 10 specific multifactorial conditions (Parkinson disease, late-onset Alzheimer disease, celiac disease, α-1 antitrypsin deficiency, early-onset primary dystonia, factor XI deficiency, Gaucher disease type 1, glucose-6-phosphate dehydrogenase deficiency, hereditary hemochromatosis, and hereditary thrombophilia).2 The genetic health risk tests authorized by the FDA provide information on an individual’s risk of developing a condition. This is based on the presence or absence of a limited list of genetic variants in the sample, which are statistically enriched in affected versus healthy cohorts but not necessarily causal of the conditions because additional factors such as environment and lifestyle influence an individual’s risk. None of the genes associated with these conditions are comprehensively sequenced or analyzed in DTC tests, nor do the tests include all of the genes that have been associated with these conditions. For example, 23andMe’s genetic health risk test reports on just one variant in each of two genes linked to Parkinson disease: LRRK2 and GBA.3 However, there are additional known pathogenic variants in these two genes as well as additional genes clinically associated with Parkinson disease that 23andMe does not report on, such as SNCA and PARK2/PARKIN.4 Therefore, the consumer is not provided with a comprehensive genetic risk assessment.

In contrast, clinical diagnostic genetic tests are ordered by a patient’s medical provider and are used to identify or rule out a specific genetic condition. One example is clinical testing for the BRCA1 and BRCA2genes. If an individual has a pathogenic variant in one of these genes, it is considered diagnostic for hereditary breast and ovarian cancer syndrome, whether or not she or he has a personal diagnosis of cancer. Diagnostic tests are generally comprehensive because the full coding sequences of all genes associated with a disease are analyzed. The test results are intended to be used by a patient’s medical provider to guide disease management or surveillance.

While the FDA currently prohibits most DTC companies from offering diagnostic genetic tests, some companies provide customers their raw genotyping data if requested, which may include variants in genes associated with Mendelian diseases, including those recommended by the American College of Medical Genetics and Genomics to be reported as incidental or secondary findings in genomic testing. These genes are implicated in highly penetrant genetic disorders for which surgical or other interventions aimed at preventing or significantly reducing morbidity and mortality are available to pathogenic variant carriers.5Identification of a pathogenic variant in one of these genes could be diagnostic of a medical condition with potential implications for an individual’s medical management.

The raw data are often accompanied by a disclaimer that the information is neither validated for accuracy nor intended for medical use. While DTC companies do not provide interpretation of the raw data, patients can access interpretation services through third-party companies, which may charge a fee.6 One recent study on such third-party companies found that several operate by querying publicly available databases, such as dbSNP, and reporting the classification provided in the database, despite reports that the majority of classifications in some publicly available databases are incorrect.67 As a result, returned results may interpret particular single-nucleotide polymorphisms as pathogenic, even though clinical laboratories may classify the same variants as unknown significance, likely benign variants, or benign polymorphisms. In addition, they are providing information to the consumer with the assumption that variants in the raw data are true calls and not false positives. The misinterpretation and potential inaccuracy of the raw data pose substantial risks to individuals who obtain this type of information from a DTC company. For these reasons, medical providers should order confirmatory genetic testing from an experienced clinical diagnostic laboratory to guide patients’ medical care.8910

What drives a consumer to pursue DTC genetic testing, their perceived usefulness of the final results, their understanding of how comprehensive a test may or may not have been, and the utilization of a genetic counselor or another health-care provider vary widely.1112 DTC results may lead to healthy changes in lifestyle and/or diet,13 but could also result in unfavorable emotions, including anxiety when obtaining unexpected information and disappointment in a lack of comprehensive diagnostic analysis.12 Regardless of whether a health-care provider is involved with the initial ordering of a patient’s DTC genetic test, the results can lead to important health-related discussions with medical providers. With the ever-growing shortage of genetic counselors and other highly trained genetic professionals, there is concern regarding how DTC test results are interpreted and used among medical providers who often have minimal genetic training.11 It is therefore imperative that consumers, as well as their medical provider(s), are aware of the wide array of limitations to this type of genetic testing, especially in regard to an individual’s clinical management. Recent studies have started to evaluate pre- and post-DTC testing encounters with health-care providers including genetic counselors;14 however, to our knowledge, no studies have described outcomes of raw data confirmatory testing referrals to clinical diagnostic laboratories. We aimed to investigate the types of cases referred to our clinical diagnostic laboratory and evaluate the concordance of confirmatory test results for cases with variants identified in the raw data by DTC genetic testing. We also aimed to investigate whether our variant classification was in agreement with that provided by the DTC testing company or third-party interpretation service.15


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