Genetic testing in critically ill adults yields unexpected diagnoses — and exposes stark gaps for Black patients

When DNA testing arrives in the adult ICU, the results can be startling

Genetic testing is now routine for many newborns and has transformed care for some critically ill children. For adults, however, sequencing has rarely been part of the diagnostic toolkit in intensive care. A new retrospective study of exome sequencing in adults aged 18–40 who were admitted to intensive care units suggests that overlooking genetic evaluation in adults can miss diagnoses with immediate clinical relevance — and that the impact of that omission is not spread evenly across racial groups.

The study examined whole-exome data from 365 adults with ICU admissions and found a diagnostic genetic variant relevant to the admission in roughly one-quarter of patients. Almost half of those genetic diagnoses were unknown to patients and their clinicians at the time of ICU care, and more than three-quarters of the detected diagnoses carried specific recommendations that could alter medical management. The paper also reports a striking disparity in prior documentation of genetic diagnoses: more than 60% of White patients had relevant genetic diagnoses recorded before or during hospitalization, compared with fewer than one-quarter of Black patients. These differences were not explained by age or by overall rates at which the test returned a diagnosis.

Why these findings matter

The headline numbers matter for two reasons. First, the diagnostic yield — about 24% — is far higher than many clinicians expect for adults, and similar to results seen in pediatric critical care studies. That implies that Mendelian or other genetic conditions remain a plausible cause of severe, undiagnosed illness well into adulthood. Second, because a large share of the diagnoses were previously unknown, there is a real chance to change patient care if sequencing is integrated into adult critical care workflows. In the study cohort, three out of four diagnostic results pointed to concrete, actionable management steps, ranging from medication choices to surveillance for complications linked to a genetic condition.

Disparities in prior diagnosis — not in who carries actionable variants

Notably, the study did not find that Black patients were inherently less likely to carry detectable genetic conditions. Instead, the disparity showed up in whether a relevant genetic diagnosis had already been documented in the electronic medical record when patients arrived in the ICU. White patients were far more likely to have a diagnosis recorded; Black patients were much less likely to have had prior genetic evaluation or documentation. That suggests differential access to genetics services, variable referral practices, or gaps in outpatient follow-up rather than biological differences in disease prevalence.

How the genetics pipeline amplifies inequality

Several structural factors help explain why prior genetic diagnoses are less common among Black patients. Outpatient access to clinical genetics varies with geography, insurance and referral patterns; some communities have long waits or no nearby specialists. Beyond access, the tools used to interpret DNA are themselves shaped by historical sampling: population databases and reference panels contain disproportionately many people of European descent, increasing the likelihood that variants found in people of non-European ancestry are classified as "variants of uncertain significance." In practice, that means nonwhite patients often receive less definitive answers from the same tests. Large-scale studies of genetic testing and reclassification show that nonwhite patients receive more uncertain results and that resolving those uncertainties requires additional clinical, family, and experimental evidence — which is not always available.

Clinical consequences and the problem of undocumented diagnoses

The study also examined outcomes. Patients whose genetic diagnoses were documented in their charts before or during admission tended to have different trajectories than those whose diagnostic exome results were previously unknown, including differences in length of ICU stay and a non-significant trend toward lower mortality for patients with known diagnoses. While the mortality differences did not reach statistical significance in this cohort, the pattern raises an alarm: undocumented genetic diagnoses — and the missed opportunities they represent — may contribute to worse outcomes for patients who already face barriers to care.

What would it take to close the gap?

• Wider and fairer access to genetic evaluation. Making rapid or expedited sequencing available in adult acute-care settings could reduce the number of patients who enter the hospital with an undiagnosed, actionable genetic condition. But access must be equitable: outreach, insurance coverage, and streamlined referral pathways are needed so that disadvantaged populations benefit, too.
• Better representation in reference data. Laboratories and researchers must continue to expand the diversity of genomic databases so that variant interpretation improves for people of all ancestries. Studies of reclassification and VUS rates show that nonwhite individuals carry a higher burden of uncertainty because the underlying datasets are biased; fixing that requires deliberate sampling, data sharing, and funding.
• Consistent collection and use of race, ethnicity and ancestry data. Clinical genetics currently lacks standardized practices for how to collect and apply these measures. Harmonized approaches would reduce misclassification and make it easier to identify and address inequities.
• Clear pathways for results to reach clinicians and patients. Discovering a genetic diagnosis is only useful if it is communicated, documented, and integrated into care plans. That means workflows for EHR integration, genetic counseling, family cascade testing, and follow-up are central to realizing the benefit of sequencing in adults.

Where this leaves clinicians, patients and policy makers

The new evidence shifts the conversation about sequencing: instead of seeing genetic testing as primarily a pediatric tool, the field must recognize its potential role among adults with unexplained severe illness. At the same time, the findings are a reminder that deploying a powerful technology without attention to equity risks amplifying existing disparities. If sequencing is to improve outcomes for all patients, its implementation needs to be paired with policies that expand access, diversify reference datasets, standardize data collection, and close the loop between laboratories, clinicians and patients.

Bottom line

Exome sequencing in the adult ICU can reveal diagnoses that change care — even in patients long past childhood — but the benefits are currently unequally distributed. Addressing the pipeline of access, interpretation and documentation is essential if genetic medicine is to realize its promise for every patient, regardless of background.

Mattias Risberg is a Cologne-based reporter for Dark Matter covering genetics, data-driven investigations and health policy. He holds an MSc in Physics and a BSc in Computer Science from the University of Cologne.