Opioid Use Disorder Genetic Test Accuracy Study Questions

Opioid abuse, specifically opioid use disorder (OUD), continues to be a major threat to US public health, with more than 6 million Americans age 12 and older meeting criteria for OUD in 2022. Efforts to crisis mitigation include the development of genetic tests to identify individuals at greater risk for OUD.

New research, published today in JAMA Network Open, challenges the utility of 15 genetic variants from an algorithm intended to predict OUD risk that was recently granted premarket approval by the Food and Drug Administration. He found that the test could lead to both false positives and false negatives.

The study was led by Christal Davis, PhD, a postdoctoral fellow at the Philadelphia-based Crescenz VA Medical Center, 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, particularly given the complex nature of psychiatric conditions, including OUD. The potential harms resulting from a faulty genetic test for OUD include both false negatives and false positives.”

Henry Kranzler, MD, Professor of Psychiatry and Director of the Center for Addiction Studies

For example, if the test incorrectly identifies patients as being at low risk for OUD, they may have a false sense of security when taking opioids, and providers may prescribe opioids to those who could become addicted. Patients who mistest for high risk of OUD may be denied an effective form of pain relief, in addition to potentially dealing with stigma.

The case-control study was based on health registry data from more than 450,000 opioid-exposed participants in the Million Veteran Program (MVP), including more than 33,000 people with OUD. It showed that the 15 single nucleotide variants (SNVs) hypothesized to predict OUD risk were not useful for detecting OUD, as they had high false-negative and false-positive rates. With 47 out of 100 cases incorrectly identified, the results are equivalent to a coin toss.

A related letter from a group of geneticist psychiatrists, 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 important environmental contribution to psychiatric disorders and how differences in an individual’s genetic background and life experiences must be taken into account when predicting risk for OUD or other psychiatric disorders.

This study was supported primarily 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 a grant provided by awards I01 BX003341 and IK2 CX002336 from the VA; the VISN Center for Research, Education, and Clinical Mental Illness 4. grant K01 AA028292 from the National Institute on Alcohol Abuse and Alcoholism and grant P30 DA046345 from the National Institute on Drug Abuse.