Do you know: The science behind genetic testing to identify opioid abuse risk is not yet proven
in 2025
Opioid abuse and specifically opioid use disorder (OUD) continues to be a significant threat to US public health, with more than 6 million Americans aged 12 and older meeting criteria for OUD in 2022. Efforts to mitigate the crisis have included genetic engineering. test to identify individuals most at risk of OUD. New research, out today i JAMA Open Network, questions the usefulness of 15 genetic variants from an algorithm intended to predict OUD risk that was recently granted premarketing approval by the Food and Drug Administration. It has been found that the test can lead to false positive and false negative results.
The study was led by Christal Davis, PhD, a postdoctoral fellow at the Crescenz VA Medical Center located in Philadelphia and Henry Kranzler, MD, professor of Psychiatry and director of the Center for Addiction Studies.
“These findings highlight the need for more robust and complete data, especially given the complex nature of psychiatric conditions, including OUD,” Kranzler said. “Potential harms resulting from faulty genetic testing for OUD include false negatives and false positives.”
For example, if the test incorrectly identifies patients as being at low risk of OUD, they may have a false sense of security in taking opioids, and providers may prescribe opioids to those who may become addicted. Patients who falsely test for a high risk of OUD could be denied an effective form of pain relief, as well as face stigma.
The case-control study used health record data from more than 450,000 participants with opioid exposure in the Million Veteran Program (MVP), including more than 33,000 individuals with OUD. It showed that the 15 single nucleotide variants (SNVs) proposed to predict OUD risk were not useful in identifying OUD, as they had high rates of false negative and false positive results. With 47 out of 100 cases misidentified, the results are equivalent to tossing a coin.
A related letter from a group of psychiatric geneticists, including Drs. Davis and Kranzler, recently published in Lancet Psychiatry. It outlines key factors that regulators should consider for this and future proposed genetic testing for OUD and other psychiatric disorders. These considerations include the significant environmental contribution to psychiatric disorders and how differences in a person’s genetic ancestry and life experiences need to be considered when predicting risk for OUD or other psychiatric disorders.
This study was primarily supported by the Million Veteran Program, a research initiative of the US Department of Veterans Affairs that studies how genes, lifestyle, military experiences, and other exposures affect health and well-being in veterans, with grant support provided by awards I01 BX003341 and IK2 CX002336 from the VA; the Mental Illness Research, Education and Clinical Center VSN 4; grant K01 AA028292 from the National Institute on Alcohol Abuse and Alcoholism, and grant P30 DA046345 from the National Institute on Drug Abuse.