The misuse of opioids, particularly opioid use disorder (OUD), remains a major public health issue in the U.S., affecting over 6 million Americans aged 12 and older who met the criteria for OUD in 2022. To address this crisis, genetic testing has been developed to pinpoint individuals at the highest risk for OUD. However, new research published today in JAMA Network Open raises doubts about the efficacy of a specific algorithm utilizing 15 genetic variants, which recently received pre-marketing approval from the Food and Drug Administration for predicting OUD risk. This study revealed that the testing could result in both false positives and false negatives.
Christal Davis, PhD, a postdoctoral fellow at the Crescenz VA Medical Center in Philadelphia, along with Henry Kranzler, MD, a professor of Psychiatry and director of the Center for Studies of Addiction, conducted the study.
According to Kranzler, “These findings highlight the necessity for more comprehensive and reliable data, especially considering the complexity of psychiatric disorders like OUD. The risks associated with an unreliable genetic test for OUD include both false negatives and false positives.”
For instance, if a test incorrectly classifies individuals as low-risk for OUD, they might misuse opioids due to a false sense of safety, leading healthcare providers to prescribe opioids to those who could become dependent. Conversely, patients incorrectly labeled as high-risk for OUD might be denied effective pain management and face societal stigma.
This case-control study analyzed health records from over 450,000 participants with exposure to opioids in the Million Veteran Program (MVP), which included more than 33,000 individuals with OUD. The findings indicated that the 15 single nucleotide variants (SNVs) intended to predict OUD risk were ineffective, demonstrating a high rate of both false negatives and false positives—resulting in 47 out of 100 cases being misclassified, akin to a coin flip.
In a related letter published in *Lancet Psychiatry*, a team of psychiatric geneticists, including Drs. Davis and Kranzler, emphasized essential factors that regulators should evaluate for this and future proposed genetic testing for OUD and similar psychiatric conditions. These factors include the substantial impact of environmental influences on psychiatric disorders, as well as the significance of genetic ancestry and individual life experiences in assessing OUD risk or other psychiatric issues.
This research was primarily funded by the Million Veteran Program, an initiative by the U.S. Department of Veterans Affairs aimed at understanding how genetics, lifestyle choices, military background, and other exposures affect health and well-being in veterans. Additional grant support was provided through awards I01 BX003341 and IK2 CX002336 from the VA; the VISN 4 Mental Illness Research, Education and Clinical Center; grant K01 AA028292 from the National Institute on Alcohol Abuse and Alcoholism; and grant P30 DA046345 from the National Institute on Drug Abuse.
