Efforts to address the opioid crisis have increasingly turned to genetic testing, with the goal of identifying individuals most at risk for opioid use disorder (OUD). However, new research published in JAMA Network Open casts doubt on the reliability of a genetic test recently granted pre-marketing approval by the Food and Drug Administration (FDA). The study highlights significant limitations in the test’s ability to accurately predict OUD risk, raising concerns about its clinical utility.
Evaluating the Genetic Test
The genetic test in question analyzes 15 single nucleotide variants (SNVs) and uses an algorithm to estimate an individual’s susceptibility to OUD. The study, conducted by researchers from the University of Pennsylvania Perelman School of Medicine and Crescenz VA Medical Center, examined the test's performance in predicting OUD risk using health records from over 450,000 participants in the Million Veteran Program (MVP), including 33,000 individuals with OUD.
The results were sobering: the test misidentified risk in 47 out of 100 cases, effectively performing no better than chance. “These findings underscore the need for more robust and complete data, particularly given the complex nature of psychiatric conditions, including OUD,” said Henry Kranzler, director of the Center for Studies of Addiction and co-author of the study.
Risks of Misclassification
False positive and false negative results from such genetic testing could have serious consequences. Patients incorrectly identified as low-risk might underestimate their susceptibility to addiction, potentially leading to inappropriate opioid prescribing. Conversely, those wrongly flagged as high-risk could be denied effective pain management or face stigmatization.
Psychiatric conditions like OUD are complex, and influenced by a mix of genetic, environmental, and personal factors. These complexities challenge the notion that a small number of genetic variants can provide reliable predictions.
Broader Implications for Psychiatric Genetic Testing
The study’s findings contribute to ongoing debates about the role of genetic testing in psychiatry. In a related letter published in Lancet Psychiatry, Kranzler, Christal Davis (lead author and postdoctoral fellow at the Crescenz VA Medical Center), and other psychiatric geneticists emphasized the importance of considering environmental factors and genetic ancestry when designing and evaluating tests for psychiatric disorders. They argued that regulators need to account for these variables to avoid misleading conclusions and harmful outcomes.
The case-control study represents one of the largest evaluations of genetic risk prediction for OUD, leveraging the robust dataset of the MVP. Despite the test’s FDA pre-marketing approval, the researchers caution against its clinical application until further evidence supports its reliability.
Publication Details
Davis CN, Jinwala Z, Hatoum AS, et al. Utility of Candidate Genes From an Algorithm Designed to Predict Genetic Risk for Opioid Use Disorder. JAMA Netw Open. 2025;8(1):e2453913. doi:10.1001/jamanetworkopen.2024.53913
Evaluating the Genetic Test
The genetic test in question analyzes 15 single nucleotide variants (SNVs) and uses an algorithm to estimate an individual’s susceptibility to OUD. The study, conducted by researchers from the University of Pennsylvania Perelman School of Medicine and Crescenz VA Medical Center, examined the test's performance in predicting OUD risk using health records from over 450,000 participants in the Million Veteran Program (MVP), including 33,000 individuals with OUD.
The results were sobering: the test misidentified risk in 47 out of 100 cases, effectively performing no better than chance. “These findings underscore the need for more robust and complete data, particularly given the complex nature of psychiatric conditions, including OUD,” said Henry Kranzler, director of the Center for Studies of Addiction and co-author of the study.
Risks of Misclassification
False positive and false negative results from such genetic testing could have serious consequences. Patients incorrectly identified as low-risk might underestimate their susceptibility to addiction, potentially leading to inappropriate opioid prescribing. Conversely, those wrongly flagged as high-risk could be denied effective pain management or face stigmatization.
Psychiatric conditions like OUD are complex, and influenced by a mix of genetic, environmental, and personal factors. These complexities challenge the notion that a small number of genetic variants can provide reliable predictions.
Broader Implications for Psychiatric Genetic Testing
The study’s findings contribute to ongoing debates about the role of genetic testing in psychiatry. In a related letter published in Lancet Psychiatry, Kranzler, Christal Davis (lead author and postdoctoral fellow at the Crescenz VA Medical Center), and other psychiatric geneticists emphasized the importance of considering environmental factors and genetic ancestry when designing and evaluating tests for psychiatric disorders. They argued that regulators need to account for these variables to avoid misleading conclusions and harmful outcomes.
The case-control study represents one of the largest evaluations of genetic risk prediction for OUD, leveraging the robust dataset of the MVP. Despite the test’s FDA pre-marketing approval, the researchers caution against its clinical application until further evidence supports its reliability.
Publication Details
Davis CN, Jinwala Z, Hatoum AS, et al. Utility of Candidate Genes From an Algorithm Designed to Predict Genetic Risk for Opioid Use Disorder. JAMA Netw Open. 2025;8(1):e2453913. doi:10.1001/jamanetworkopen.2024.53913