A new study led by researchers at Queen Mary University of London reveals that genetic testing for just three specific genes could help prevent up to 75% of adverse drug reactions (ADRs) prior to prescribing drugs. The research, published in PLOS Medicine, analyzed more than 1.3 million ADR reports submitted to the U.K. Medicines and Healthcare Products Regulatory Agency (MHRA), to show how pharmacogenomic (PGx) testing could reduce the risk of severe, potentially fatal, side effects caused by certain medications.
“It is important to understand the landscape of side effects reported nationally over the past half century to elucidate the impact that prospective use of genetic testing to personalize prescribing may have in the U.K.,” said lead author Emma Magavern, clinical academic lecturer at Queen Mary’s Centre for Clinical Pharmacology and Precision Medicine.
The study analyzed ADR reports submitted to the Yellow Card scheme between 1963 and 2024, revealing a significant association between certain pharmacokinetic genes and the risk of ADRs. These genes are responsible for how the body metabolizes medications, and variations in these genes can lead to individuals being at higher risk for side effects.
Adverse drug reactions are a significant concern for healthcare systems worldwide. In the U.K. alone, the MHRA’s Yellow Card scheme—a centralized reporting method for ADRs—has recorded over a million ADR reports in the past six decades. The estimated additional care costs associated with ADRs are more than £2 billion annually. The study revealed that of the more than 1.3 million ADRs, approximately 9% are linked to medications where genetic information could inform safer prescribing practices. Of these, 75% are associated with just three genes: CYP2C19, CYP2D6, and SLCO1B1, which affect how the body processes medications.
The findings are particularly relevant for psychiatric drugs, which were disproportionately represented in the reports and accounted for 47% of ADRs. “Psychiatric medication-associated ADRs were the highest prevalence across organ systems,” the researchers wrote. “Our analysis of national pharmacovigilance reporting at scale shows that the greatest potential area of intervention by specialty to mitigate Yellow Card reported ADRs in the U.K. may be within psychiatry.”
The study also showed a high prevalence of ADRs—about 24%—associated with the prescription of cardiovascular medications.
This study provides further evidence for the potential benefits of integrating PGx testing into clinical practice. Previous research, including the PREPARE trial, demonstrated that prospective genetic testing could reduce ADRs by as much as 30%.
This study noted that PGx testing could disproportionately benefit certain populations. The genetic variants in CYP2D6 and CYP2C19 show significant differences in the prevalence of predicted extreme metabolizer types—those people who are either poor metabolizers of a drug or are extreme metabolizers.
“It is unfortunate that ancestry data was not available for these Yellow Card reports; however, based on what is known about polymorphism frequencies in these genes, ADRs associated with typical metabolizer types of associated drugs will be more frequent in under-represented African and Asian ancestry groups,” the researchers wrote. “Therefore, piloting PGx with these few selective genes would not only capture 75% of all mitigatable ADRs but would also disproportionately benefit these populations therefore targeting existing health inequalities.”
Based on their findings, the researchers are calling for pilot studies in the U.K.’s NHS to test the impact of PGx-guided prescribing with the hope that PGx testing could become a routine part of clinical care.
“Our findings suggest that a limited panel of three pharmacogenes could potentially pre-emptively identify most of those at risk of ADRs and avoid significant patient harm and hospitalization,” the researchers wrote. The researchers acknowledged that further work is needed to develop and refine diagnostic tools to identify these genetic variants in the clinical setting, and to investigate how these tools can be integrated into everyday practice.
