Results from direct-to-consumer genetic testing for medical health risk: accurate or erroneous?

Researchers at HudsonAlpha contribute valuable information to the ongoing discussion surrounding the accuracy of direct-to-consumer genetic testing

October 14, 2020 (Huntsville, Ala.) – Direct-to-consumer (DTC) genetic testing became popular in the 2000s when companies touted that by merely submitting a saliva sample, individuals could discover they were distantly related to a United States President or a member of the royal family. Recently, its popularity rose again after the Golden State Killer was identified by DNA testing technology that mapped DNA from several crime scenes to DNA from his distant relatives that had been submitted to a public database, allowing investigators to narrow in on a suspect.

In an effort to maintain their momentous growth, DTC genetic testing companies are moving into unchartered territory by offering health-related genetic test results directly to individuals without the counsel of a physician. Although these companies make it clear to their customers that results received from their screening tests do not diagnose cancer or any other health conditions or determine medical action, the results, whether negative or positive, still have an impact on the individual receiving them.

Providing false positive results to an individual, or telling them they have a disease-related genetic variant when they do not, has potentially damaging repercussions such as emotional distress and unnecessary medical interventions. On the flip side, false negatives lead to a mistaken reassurance of a lack of genetic disease risk, when in fact the individual could have such a risk.

Determining the effectiveness of genetic health screening in individuals without a medical indication for testing

There have been several reports that suggest DTC tests lead to the identification of false positive variants that appear to be medically relevant but fail confirmatory testing.

Researchers in Greg Cooper’s lab at HudsonAlpha Institute for Biotechnology, along with collaborators at the University of Alabama at Birmingham (UAB), found similar false positive results during a recent study.

The results, which were recently published in Genetics in Medicine, highlight findings on the effectiveness of population-based genomic screening in Alabama. The study was part of a partnership between HudsonAlpha and UAB called the Alabama Genomic Health Initiative (AGHI). The program, launched in 2017, is funded by the State of Alabama and led by Bruce Korf, MD, PhD (UAB), Greg Barsh, MD, Phd (HudsonAlpha), and Matthew Might, PhD (UAB). AGHI aims to conduct genetic screening for a broad population of individuals who have no specific medical indication for testing, meaning they do not have a significant personal or family history suggestive of a genetic condition. The goal of AGHI is to determine the utility of genetic screening in disease prevention, management, and treatment.

“We believe that readily accessible genetic testing could provide a lot of benefits to individuals and communities. However, we need to ensure that testing is done accurately, and that those who receive it have a clear understanding of potential errors and limitations,” says HudsonAlpha Faculty Investigator Greg Cooper, PhD.

At the time of publication, the team had screened 5,369 Alabamians in an attempt to identify genetic variation that may be relevant to participants’ health. The genetic screens were conducted using a screening array designed to genotype more than 654,000 variants, including ~160,000 rare variants that may increase an individual’s susceptibility to a disease.

Variants identified by the array were validated by DNA sequencing before the results were returned to the study participants. This is where things got interesting. While researchers were able to confirm medically-relevant variants in ~1.5% of study participants, they also discovered that an additional ~1.5% of participants were flagged as having a medically-relevant variant that turned out to be false positives, meaning they could not be confirmed by DNA sequencing. If confirmatory testing had not been conducted, roughly half of the individuals with array-identified medically-relevant findings would have been falsely told that they had an increased risk of a serious condition like cancer or heart disease.

“While we have known that detection of rare genetic variation via array-based methods can be problematic, our work further highlights the issue,” says Kevin Bowling, PhD, Senior Scientist in the Cooper lab and first author of the publication. “We demonstrate the necessity for clinical confirmation of variants that are identified by DTC genetic testing or population screening, as they may affect clinical decision-making.”

By analyzing self-reported race and ethnicity data, the group also found that African-American individuals were more likely than European Americans to receive a false positive result. This likely reflects reduced representation of non-European individuals in clinical and research genetic databases.

Together, all of the observations from this study support the notion that array-detected disease-linked variants, such as those detected in DTC genetic tests, should be confirmed by an additional method in a clinical genetics lab prior to returning results to patients, especially for individuals of under-represented minorities.

Learn more about the various types of genetic tests and what they can uncover:

“Genetics in Medicine” is the official journal of the American College of Medical Genetics and Genomics (ACMG).

About HudsonAlpha: HudsonAlpha Institute for Biotechnology is a nonprofit institute dedicated to developing and applying scientific advances to health, agriculture, learning, and commercialization. Opened in 2008, HudsonAlpha’s vision is to leverage the synergy between discovery, education, medicine, and economic development in genomic sciences to improve the human condition around the globe. The HudsonAlpha biotechnology campus consists of 152 acres nestled within Cummings Research Park, the nation’s second largest research park. The state-of-the-art facilities co-locate nonprofit scientific researchers with entrepreneurs and educators. HudsonAlpha has become a national and international leader in genetics and genomics research and biotech education and fosters more than 40 diverse biotech companies on campus. To learn more about HudsonAlpha, visit