News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel

News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
Sign In

Mayo Clinic Scientists Develop AI Tool That Can Determine If Gut Microbiome is Healthy

Although it is a non-specific procedure that does not identify specific health conditions, it could lead to new biomarkers that clinical laboratories could use for predictive healthcare

Researchers from the Mayo Clinic recently used artificial intelligence (AI) to develop a predictive computational tool that analyzes an individual’s gut microbiome to identify how a person may experience improvement or deterioration in health. 

Dubbed the Gut Microbiome Wellness Index 2 (GMWI2), Mayo’s new tool does not identify the presence of specific health conditions but can detect even minor changes in overall gut health.

Built on an earlier prototype, GMWI2 “demonstrated at least 80% accuracy in differentiating healthy individuals from those with any disease,” according to a Mayo news release. “The researchers used bioinformatics and machine learning methods to analyze gut microbiome profiles in stool samples gathered from 54 published studies spanning 26 countries and six continents. This approach produced a diverse and comprehensive dataset.”

The Mayo researchers published their findings in the journal Nature Communications titled, “Gut Microbiome Wellness Index 2 Enhances Health Status Prediction from Gut Microbiome Taxonomic Profiles.”

“Finally, we have a standardized index to quantitatively measure how ‘healthy’ a person’s gut microbiome is,” said Jaeyun Sung, PhD, a computational biologist at the Mayo Clinic Center for Individualized Medicine: Microbiomics Program and senior author of the study in the news release.

“Our tool is not intended to diagnose specific diseases but rather to serve as a proactive health indicator,” said senior study author Jaeyun Sung, PhD (above), a computational biologist at the Mayo Clinic Center for Individualized Medicine: Microbiomics Program in the news release ease. “By identifying adverse changes in gut health before serious symptoms arise, the tool could potentially inform dietary or lifestyle modifications to prevent mild issues from escalating into more severe health conditions, or prompt further diagnostic testing.” For microbiologists and clinical laboratory managers, this area of new knowledge about the human microbiome may lead to multiplex diagnostic assays. (Photo copyright: Mayo Clinic.)

Connecting Specific Diseases with Gut Microbiome

Gut bacteria that resides in the gastrointestinal tract consists of trillions of microbes that help regulate various bodily functions and may provide insights regarding the overall health of an individual. An imbalance in the gut microbiome is associated with an assortment of illnesses and chronic diseases, including cardiovascular issues, digestive problems, and some cancers and autoimmune diseases

To develop GMWI2, the Mayo scientists provided the machine-learning algorithm with data on microbes found in stool samples from approximately 8,000 people collected from 54 published studies. They looked for the presence of 11 diseases, including colorectal cancer and inflammatory bowel disease (IBS). About 5,500 of the subjects had been previously diagnosed with one of the 11 diseases, and the remaining people did not have a diagnosis of the conditions. 

The scientists then tested the efficacy of GMWI2 on an additional 1,140 stool samples from individuals who were diagnosed with conditions such as pancreatic cancer and Parkinson’s disease, compared with those who did not have those illnesses.

The algorithm gives subjects a score between -6 and +6. People with a higher GMWI2 score have a healthier microbiome that more closely resembles individuals who do not have certain diseases.

Likewise, a low GMWI2 score suggests the individual has a gut microbiome that is similar to those who have specific illnesses. 

Highly Accurate Results

According to their study, the researchers determined that “GMWI2 achieves a cross-validation balanced accuracy of 80% in distinguishing healthy (no disease) from non-healthy (diseased) individuals and surpasses 90% accuracy for samples with higher confidence,” they wrote in Nature Communications.

Launched in 2020, the original GMWI (Gut Microbiome Wellness Index) was trained on a much smaller number of samples but still showed similar results. 

The researchers tested the enhanced GMWI2 algorithm across various clinical schemes to determine if the results were similar. These scenarios included individuals who had previous fecal microbiota transplants and people who had made dietary changes or who had exposure to antibiotics. They found that their improved tool detected changes in gut health in those scenarios as well.

“By being able to answer whether a person’s gut is healthy or trending toward a diseased state, we ultimately aim to empower individuals to take proactive steps in managing their own health,” Sung said in the news release.

The Mayo Clinic team is developing the next version of their tool, which will be known as the Gut Microbiome Wellness Index 3. They plan to train it on at least 12,000 stool samples and use more sophisticated algorithms to decipher the data.

More research and studies are needed to determine the overall usefulness of Mayo’s Gut Microbiome Wellness Index and its marketability. Here is a world-class health institution disclosing a pathway/tool that analyzes the human microbiome to identify how an individual may be experiencing either an improvement in health or a deterioration in health.

The developers believe it will eventually help physicians determine how patients’ conditions are improving or worsening by comparing the patients’ microbiomes to the profiles of other healthy and unhealthy microbiomes. As this happens, it would create a new opportunity for clinical laboratories to perform the studies on the microbiomes of patients being assayed in this way by their physicians.  

—JP Schlingman

Related Information:

Mayo Researchers Develop Tool That Measures Health of a Person’s Gut Microbiome

Gut Microbiome Wellness Index 2 Enhances Health Status Prediction from Gut Microbiome Taxonomic Profiles

Stanford University Scientists Discover New Lifeform Residing in Human Microbiome

Researchers Use Ingestible Device to Non-Invasively Sample Human Gut Bacteria in a Development That Could Enable More Clinical Laboratory Testing of Microbiomes

Researchers from Stanford University Develop First Synthetic Human Microbiome from Scratch

100-Biomarker Lab Test for Alzheimer’s Disease Developed by Team at University of Pittsburgh

New clinical laboratory test could replace conventional spinal tap for diagnosing neurodegenerative disease

In a proof-of-concept study, University of Pittsburgh (Pitt) scientists validated a clinical laboratory test that measures more than 100 different genetic sequences associated with Alzheimer’s disease. The Pitt researchers believe the new diagnostic platform could help clinicians “capture the multifaceted nature of Alzheimer’s pathology and streamline early disease diagnostics,” according to a news release.

Clinical laboratory blood tests that detect biomarkers such as phosphorylated tau protein (pTau) have emerged in studies as diagnostic possibilities for Alzheimer’s disease, which is traditionally diagnosed using a lumbar puncture (spinal tap) procedure.

The Pitt scientists published the findings of their study titled, “Multi-Analyte Proteomic Analysis Identifies Blood-based Neuroinflammation, Cerebrovascular, and Synaptic Biomarkers in Preclinical Alzheimer’s Disease,” in the journal Molecular Neurodegeneration.

In their paper, neuroscientist Thomas Karikari, PhD, Assistant Professor of Psychiatry at  University of Pittsburgh, lead author of the study, and his research team acknowledged that progress has been made in detecting Alzheimer’s disease with blood-based biomarkers. However, they note that “two key obstacles remain: the lack of methods for multi-analyte assessments and the need for biomarkers for related pathophysiological processes like neuroinflammation, vascular, and synaptic dysfunction.”

The Pitt scientists believe the focus on so-called “classical Alzheimer’s blood biomarkers” limits exploration of neurodegenerative disease.

“Alzheimer’s disease should not be looked at through one single lens. Capturing aspects of Alzheimer’s pathology in a panel of clinically validated biomarkers would increase the likelihood of stopping the disease before any cognitive symptoms emerge,” said neuroscientist Thomas Karikari, PhD (above), Assistant Professor of Psychiatry, University of Pittsburgh, and lead author of the study in a news release. Should further studies prove Pitt’s research sound, clinical laboratories may have a replacement test for diagnosing neurodegenerative disease. (Photo copyright: University of Pittsburgh.)

120 Proteins Analyzed Simultaneously

To conduct their research, the Pitt scientists performed a proof-of-concept study on 176 blood samples from 113 adults in Pennsylvania (average age of 76.7). They analyzed the blood using the NULISAseq CNS (central nervous system) Disease Panel 120 by Alamar Biosciences of Freemont, California.

On its website, Alamar Biosciences explains that the disease panel offers neurological researchers:

  • “Multiplexed analysis of 120 neuro-specific and inflammatory proteins from 10 µl of plasma or CSF (cerebrospinal fluid).
  • Detection of “critical biomarkers—including pTau-217, GFAP (glial fibrillary acidic protein), NEFL (neurofilament light polypeptide) and alpha-synuclein.”

The NULISAseq test works with “a proprietary sequential immunocomplex capture and release mechanism and the latest advances in next-generation sequencing,” according to the company.

Inside Precision Medicine noted that the Alamar Biosciences assay enabled Pitt scientists to detect:

  • Biomarkers (usually found in CSF) “correlating with patients’ amyloid positivity status and changes in amyloid burden over time,” and,
  • Biomarkers including “neuroinflammation, synaptic function, and vascular health, which had not previously been validated in blood samples.”

“The performance of the NULISA platform was independently validated against conventional assays for classic Alzheimer’s biomarkers for each sample. Biomarker profiles over two years were also compared with imaging-based measures of amyloid, tau, and neurodegeneration,” LabMedica reported.

Opportunity to Track Alzheimer’s

Karikari sees the diagnostic platform being used to track individuals’ blood biomarker changes over time. 

In their Molecular Neurodegeneration paper, the Pitt researchers wrote, “These (results) were not limited to markers such as pTau217, p-Tau231, p-Tau181, and GFAP, the elevation of which have consistently shown strong associations with brain Aβ [amyloid beta] and/or tau load, but included novel protein targets that inform about the disease state of the individual in different pathological stages across the biological Alzheimer’s disease continuum.”

About seven million Americans are affected by Alzheimer’s disease, according to the Alzheimer’s Association, which estimated that figure will grow to 13 billion by 2050.

Further studies by Karikari may include larger samples and greater diversity among the people studied, Inside Precision Medicine noted.

“[Karikari’s] lab is developing a predictive model that correlates biomarker changes detected using NULISAseq with brain autopsy data and cognitive assessments collected over the course of several years. Their goal is to identify blood biomarkers that can help stage the disease and predict its progression, both for decision-making around clinical management and treatment plans,” the Pitt news release states.

His research was supported by the National Institute on Aging.

The Pitt scientists have developed a multiplex test that works with 100 different genetic sequences associated with Alzheimer’s. Such advances in the understanding of the human genome are giving scientists the opportunity to combine newly identified gene sequences that have a role in specific disease states.

In turn, as further studies validate the value of these biomarkers for diagnosing disease and guiding treatment decisions, clinical laboratories will have new assays that deliver more value to referring physicians and their patients.

—Donna Marie Pocius

Related Information:

Pitt Scientists Validated a New Panel for Blood Biomarkers of Alzheimer’s

Multi-Analyte Proteomic Analysis Identifies Blood-based Neuroinflammation, Cerebrovascular, and Synaptic Biomarkers in Preclinical Alzheimer’s Disease

Innovative Blood Test Validated for Comprehensive Early Alzheimer’s Diagnosis

New Blood Test Platform Simultaneously Measures Over 100 Biomarkers of Alzheimer’s Disease

Cerebrospinal Fluid and Plasma Tau as a Biomarker for Brain Tauopathy

University of Michigan National Study Finds Nearly Half of Seniors Surveyed Purchased At-Home Medical Tests and Most Plan to Buy More

Clinical laboratory executives and pathology leaders may want to develop strategies for supporting the growing numbers of at-home screening and diagnostic test users

Findings of a national poll conducted by the University of Michigan (U-M) exploring consumers’ purchases suggests seniors are becoming more comfortable with ordering and using at-home medical testing. Their choice of tests and opinions may be of interest to clinical laboratory executives, pathologists, and primary care physicians considering programs to support self-test purchasers.

Conducted through U-M’s Institute for Healthcare Policy and Innovation, the National Poll on Healthy Aging study involved 2,163 adults over age 50, who responded to questions online or by phone in January 2022.

The researchers found that 48% of adults, ages 50 to 80, purchased at least one at-home medical test, and that 91% of the buyers indicated intentions to purchase another test in the future, according to a U-M news release.

The researchers published their study, “Use of At-Home Medical Tests among Older US Adults: A Nationally Representative Survey,” in The Journal of Health Care.

In their paper, they note that “validity, reliability, and utility of at-home tests is often uncertain.” Further, understanding and responding to test results—especially since caregivers may not have ordered them—could lead to “a range of unintended consequences,” they wrote.

“As a primary care doctor, I would want to know why my patient chose to take an at-home test that I didn’t order for them. We also need to understand in greater detail why folks use at-home tests instead of traditional means, beyond convenience,” said the U-M study’s lead author Joshua Rager, MD, a research scientist at William M. Tierney Center for Health Services Research at Regenstrief Institute, who is now an assistant professor of medicine, Indiana University, in a news release. The findings of the U-M study will be of interest to clinical laboratory executives and pathology leaders. (Photo copyright: Regenstrief Institute.)

Free COVID-19 Tests Ignite At-Home Testing

In their Journal of Health Care paper, the U-M researchers speculate that curiosity in at-home testing may have been propelled by the offer of free COVID-19 tests by the US government starting in 2021 during the pandemic.

They also noted the different ways at-home test kits are performed by healthcare consumers. Some, such as COVID-19 rapid antigen tests, return results to users in a few moments similar to pregnancy tests. Others involve self-collecting specimens, such as a stool sample, then sending the specimen to a clinical laboratory for analysis and results reporting to physicians.

Abbott’s BinaxNOW COVID-19 Ag Card (SARS-CoV-2 test) and Exact Sciences’ Cologuard (colorectal cancer screening test) are examples of two different styles of testing.

Of those older adults who participated in U-M’s National Poll on Healthy Aging study, the following bought at-home medical tests online or from pharmacies and supermarkets, according to U-M’s paper:

Opinions, Sharing of At-Home Test Results Vary

As to perceptions of at-home medical testing by users, when polled on their test experience, the surveyed seniors reported the following:

  • 75.1% perceived at-home medical tests to be more convenient than conventional medical tests.
  • 59.9% believe the tests “can be trusted to give reliable results.”
  • 54.8% believe the tests “are regulated by government.”
  • 66% called them a “good value.”
  • 93.6% indicated results “should be discussed with my doctor.”

Inconsistency in how people shared test results with their healthcare providers was a concern voiced by the researchers.

“While nearly all patients who had bought an at-home cancer screening test shared the results with their primary care provider, only about half of those who tested for an infection other than COVID-19 had. This could have important clinical implications,” the researchers wrote in their paper.

Confusion over Government Regulation

The U-M study also revealed consumer misunderstanding about government regulation of at-home clinical laboratory tests purchased over-the-counter.

The US Food and Drug Administration (FDA) cleared “some diagnostic at-home tests for over-the counter use. But many tests on the market are unregulated or under-regulated,” the authors wrote, adding, “Our results suggest, however, that patients generally believe at-home tests are regulated by government, but a substantial minority did not, which may reflect public confusion in how at-home testing is regulated.”

Women, College-Educated Buy More At-Home Tests

Purchase of at-home tests varies among groups, as follows, the news release noted:

  • 56% and 61% of older adults with a college degree or household income above $100,000, respectively, were “much more likely” to buy at-home tests than people in other income and education brackets.
  • 87% of women would buy at-home tests again compared with 76% of men.
  • 89% of college-educated people would purchase the tests again, compared with 78% of people with high school educations or less.

Future U-M research may explore consumers’ awareness/understanding concerning federal regulations of at-home testing, Rager noted.

“At-home tests could be used to address disparities in access to care. We hope these findings will inform regulators and policymakers and spark future research on this topic,” he said in the news release.

The U-M Institute for Healthcare Policy and Innovation survey results confirm that the country’s senior generations are becoming comfortable with at-home and self-testing options. As Dark Daily has previously suggested, clinical laboratories may want to develop service offerings and a strategy for supporting patients who want to perform their own lab tests at home.

—Donna Marie Pocius

Related Information:

Big Gaps Seen in Home Medical Test Use by Older Adults

Use of At-Home Medical Tests among Older US Adults: A Nationally Representative Survey

Genetic Tests Are Detecting Prevalence of Bird Flu Virus in US Wastewater and Allowing Officials to Track its Spread

Though PCR clinical laboratory testing is widely used, some scientists are concerned its specificity may limit the ability to identify all variants of bird flu in wastewater

Wastewater testing of infectious agents appears to be here to stay. At the same time, there are differences of opinion about which methodologies and clinical laboratory tests are best suited to screen for specific contagions in wastewater. One such contagion is avian influenza, the virus that causes bird flu.

Wastewater testing by public health officials became a valuable tool during the COVID-19 pandemic and has now become a common method for detecting other diseases as well. For example, earlier this year, scientists used wastewater testing to learn how the H5N1 variant of the bird flu virus was advancing among dairy herds across the country.

In late March, the bird flu was first detected in dairy cattle in Texas, prompting scientists to begin examining wastewater samples to track the virus. Some researchers, however, expressed concerns about the ability of sewage test assays to detect all variants of certain diseases.

“Right now we are using these sort of broad tests to test for influenza A viruses,” Denis Nash, PhD, Distinguished Professor of Epidemiology at City University of New York (CUNY) and Executive Director of CUNY’s Institute for Implementation Science in Population Health (SPH), told the Los Angeles Times. “It’s possible there are some locations around the country where the primers being used in these tests might not work for H5N1.” Clinical laboratory PCR genetic testing is most commonly used to screen for viruses in wastewater. (Photo copyright: CUNY SPH.)

Effectiveness of PCR Wastewater Testing

Polymerase chain reaction (PCR) tests are most commonly used to distinguish genetic material related to a specific illness such as the flu virus. For PCR tests to correctly identify a virus, the tests must be designed to look for a specific subtype. The two most prevalent human influenza A viruses are known as H1N1 (swine flu) and H3N2, which was responsible for the 1968 pandemic that killed a million people worldwide. The “H” stands for hemagglutinin and the “N” for neuraminidase.

Hemagglutinin is a glycoprotein that assists the virus to attach to and infect host cells. Neuraminidase is an enzyme found in many pathogenic or symbiotic microorganisms that separates the links between neuraminic acids in various molecules.

Avian flu is also an influenza A virus, but it has the subtype H5N1. Although human and bird flu viruses both contain the N1 signal, they do not share an H. Some scientists fear that—in cases where a PCR test only looks for H1 and H3 in wastewater—that test could miss the bird flu altogether.

“We don’t have any evidence of that. It does seem like we’re at a broad enough level that we don’t have any evidence that we would not pick up H5,” Jonathan Yoder, Deputy Director, Infectious Disease Readiness and Innovation at the US Centers for Disease Control and Prevention (CDC) told the Los Angeles Times.

The CDC asserts current genetic testing methods are standardized and will detect the bird flu. Yoder also affirmed the tests being used at all the testing sites are the same assay, based on information the CDC has published regarding testing for influenza A viruses. 

Genetic Sequencing Finds H5N1 in Texas Wastewater

In an article published on the preprint server medRxiv titled, “Virome Sequencing Identifies H5N1 Avian Influenza in Wastewater from Nine Cities,” the authors wrote, “using an agnostic, hybrid-capture sequencing approach, we report the detection of H5N1 in wastewater in nine Texas cities, with a total catchment area population in the millions, over a two-month period from March 4th to April 25th, 2024.”

The authors added, “Although human to human transmission is rare, infection has been fatal in nearly half of patients who have contracted the virus in past outbreaks. The increasing presence of the virus in domesticated animals raises substantial concerns that viral adaptation to immunologically naïve humans may result in the next flu pandemic.”

“So, it’s not just targeting one virus—or one of several viruses—as one does with PCR testing,” Eric Boerwinkle, PhD, Dean of the UTHealth Houston School of Public Health told the LA Times. “We’re actually in a very complex mixture, which is wastewater, pulling down viruses and sequencing them. What’s critical here is it’s very specific to H5N1.”

Epidemiologist Blake Hanson, PhD, Assistant Professor, Department of Epidemiology, Human Genetics, and Environmental Sciences at the UT Health Houston Graduate School of Biomedical Science, agreed with Boerwinkle that though the PCR-based methodology is highly effective at detecting avian flu in wastewater samples, the testing can do more.

“We have the ability to look at the representation of the entire genome, not just a marker component of it. And so that has allowed us to look at H5N1, differentiate it from some of our seasonal fluids like H1N1 and H3N2,” Hanson told the LA Times. “It’s what gave us high confidence that it is entirely H5N1, whereas the other papers are using a part of the H5 gene as a marker for H5.”

Human or Animal Sources

Both Boerwinkle and Hanson are epidemiologists in the team studying wastewater samples for H5N1 in Texas. They are not sure where the virus originated but are fairly certain it did not come from humans.

“Texas is really a confluence of a couple of different flyways for migratory birds, and Texas is also an agricultural state, despite having quite large cities,” Boerwinkle noted. “It’s probably correct that if you had to put your dime and gamble what was happening, it’s probably coming from not just one source but from multiple sources. We have no reason to think that one source is more likely any one of those things.”

“Because we are looking at the entirety of the genome, when we look at the single human H5N1 case, the genomic sequence has a hallmark amino acid change, compared to all of the cattle from that same time point,” Hanson said. “We do not see that hallmark amino acid present in any of our sequencing data. And we’ve looked very carefully for that, which gives us some confidence that we’re not seeing human-human transmission.”

CDC Updates on Bird Flu

In its weekly updates on the bird flu situation, the CDC reported that 48 states have outbreaks in poultry and 14 states have avian flu outbreaks in dairy cows. More than 238 dairy herds have been affected and, as of September 20, over 100 million poultry have been affected by the disease.

In addition, the CDC monitored more than 4,900 people who came into contact with an infected animal. Though about 230 of those individuals have been tested for the disease, there have only been a total of 14 reported human cases in the US.

The CDC posts information specifically for laboratory workers, healthcare providers, and veterinarians on its website.

The CDC also states that the threat from avian flu to the general public is low. Individuals at an increased risk for infection include people who work around infected animals and those who consume products containing raw, unpasteurized cow’s milk.

Symptoms of H5N1 in humans may include fever or chills, cough, headaches, muscle or body aches, runny or stuffy nose, tiredness and shortness of breath. Symptoms typically surface two to eight days after exposure.

Scientists and researchers have been seeking a reliable clinical laboratory test for disease organisms in a fast, accurate, and cost-effective manner. Wastewater testing of infectious agents could fulfill those goals and appears to be a technology that will continue to be used for tracking disease.

—JP Schlingman

Related Information:

As National Wastewater Testing Expands, Texas Researchers Identify Bird Flu in Nine Cities

Experts Blast CDC over Failure to Test Sewage for Signs of H5N1 Bird Flu Virus

From Sewage to Safety: Hospital Wastewater Surveillance as a Beacon for Defense Against H5N1 Bird Flu

The Bird Flu Outbreak Has Spread to Humans: Are We Too Late to Prevent the Next Pandemic?

Detection of Hemagglutinin H5 Influenza A Virus Sequence in Municipal Wastewater Solids at Wastewater Treatment Plants with Increases in Influenza A in Spring, 2024

Virome Sequencing Identifies H5N1 Avian Influenza in Wastewater from Nine Cities

Wastewater Analysis Continues to Be an Effective Tool for Tracking Deadly Infectious Diseases in Human Communities

Genetic Testing of Wastewater Now Common in Detecting New Strains of COVID-19 and Other Infectious Diseases

San Francisco International Airport First in the Nation to Test Wastewater for SARS-CoV-2 Coronavirus

New, Cryptic COVID-19 Lineage Found in Ohio Wastewater by Molecular Virologist Tracking Spread of SARS-CoV-2 Variants

Broad Institute of MIT and Harvard Studies Use of Polygenic Risk Scores to Evaluate Genetic Risk for 10 Diseases

Though not biomarkers per se, these scores for certain genetic traits may someday be used by clinical laboratories to identify individuals’ risk for specific diseases

Can polygenic risk scores (a number that denotes a person’s genetic predisposition for certain traits) do a better job at predicting the likelihood of developing specific diseases, perhaps even before the onset of symptoms? Researchers at the Broad Institute of MIT and Harvard (Broad Institute) believe so, and their study could have implications for clinical laboratories nationwide.

In cooperation with medical centers across the US, the scientists “optimized 10 polygenic scores for use in clinical research as part of a study on how to implement genetic risk prediction for patients,” according to a Broad Institute news release.

The research team “selected, optimized, and validated the tests for 10 common diseases [selected from a total of 23 conditions], including heart disease, breast cancer, and type 2 diabetes. They also calibrated the tests for use in people with non-European ancestries,” the news release notes.

As these markers for genetic risk become better understood they may work their way into clinical practice. This could mean clinical laboratories will have a role in sequencing patients’ DNA to provide physicians with information about the probability of a patient’s elevated genetic risk for certain conditions.

However, the effectiveness of polygenic risk scores has faced challenges among diverse populations, according to the news release, which also noted a need to appropriately guide clinicians in use of the scores.

The researchers published their study, “Selection, Optimization and Validation of 10 Chronic Disease Polygenic Risk Scores for Clinical Implementation in Diverse US Populations,” in Nature Medicine.

“With this work, we’ve taken the first steps toward showing the potential strength and power of these scores across a diverse population,” said Niall Lennon, PhD (above), Chief Scientific Officer of Broad Clinical Labs.  “We hope in the future this kind of information can be used in preventive medicine to help people take actions that lower their risk of disease.” Clinical laboratories may eventually be tasked with performing DNA sequencing to determine potential genetic risk for certain diseases. (Photo copyright: Broad Institute.)

Polygenic Scores Need to Reflect Diversity

“There have been a lot of ongoing conversations and debates about polygenic risk scores and their utility and applicability in the clinical setting,” said Niall Lennon, PhD, Chair and Chief Scientific Officer of Broad Clinical Labs and first author of the study, in the news release. However, he added, “It was important that we weren’t giving people results that they couldn’t do anything about.”

In the paper, Lennon and colleagues explained polygenic risk scores “aggregate the effects of many genetic risk variants” to identify a person’s genetic predisposition for a certain disease or phenotype.

“But their development and application to clinical care, particularly among ancestrally diverse individuals, present substantial challenges,” they noted. “Clinical use of polygenic risk scores may ultimately prevent disease or enable its detection at earlier, more treatable stages.” 

The scientists set a research goal to “optimize polygenic risk scores for a diversity of people.”

They collaborated with the Electronic Medical Records and Genomics network (eMERGE) and 10 academic medical centers that enrolled 25,000 participants in the eMERGE study. Funded by the National Human Genome Research Institute of the National Institutes of Health (NIH), the eMERGE network conducts genetic research in support of genetic medicine. 

While performing the polygenic risk score testing on participants, Broad Clinical Labs focused on 10 conditions—including cardiometabolic diseases and cancer—selected by the research team based on “polygenic risk score performance, medical actionability, and clinical utility,” the Nature Medicine paper explained. 

For each condition, the researchers:

  • Identified “exact spots in the genome that they would analyze to calculate the risk score.”
  • Verified accurate genotyping of the spots by comparing results of tests with whole genome sequences from patient blood samples.
  • Used information from the NIH’s All of Us Research Program to “create a model to calibrate a person’s polygenic risk score according to that individual’s genetic ancestry.”

The All of Us program, which aims to collect health information from one million US residents, has three times more people of non-European ancestry than other data sources developing genetic risk scores, HealthDay News reported.

20% of Study Participants Showed High Risk for Disease

To complete their studies, Broad Institute researchers processed a diverse group of eMERGE participants to determine their clinical polygenic risk scores for each of the 10 diseases between July 2022 and August 2023.

Listed below are all conditions studied, as well as the number of participants involved in each study and the number of people with scores indicating high risk of the disease, according to their published paper:

Over 500 people (about 20%) of the 2,500 participants, had high risk for at least one of the 10 targeted diseases, the study found. 

Participants in the study self-reported their race/ancestry as follows, according to the paper:

  • White: 32.8%
  • Black: 32.8%
  • Hispanic: 25.4%
  • Asian: 5%
  • American Indian: 1.5%
  • Middle Eastern: 0.9%
  • No selection: 0.8%

“We can’t fix all biases in the risk scores, but we can make sure that if a person is in a high-risk group for a disease, they’ll get identified as high risk regardless of what their genetic ancestry is,” Lennon said.

Further Studies, Scoring Implications

With 10 tests in hand, Broad Clinical Labs plans to calculate risk scores for all 25,000 people in the eMERGE network. The researchers also aim to conduct follow-up studies to discover what role polygenic risk scores may play in patients’ overall healthcare.

“Ultimately, the network wants to know what it means for a person to receive information that says they’re at high risk for one of these diseases,” Lennon said.

The researchers’ findings about disease risk are likely also relevant to healthcare systems, which want care teams to make earlier, pre-symptomatic diagnosis to keep patients healthy.

Clinical laboratory leaders may want to follow Broad Clinical Labs’ studies as they perform the 10 genetic tests and capture information about what participants may be willing to do—based on risk scores—to lower their risk for deadly diseases.

—Donna Marie Pocius

Related Information:

Genetic Risk Prediction for 10 Chronic Diseases Moves Closer to the Clinic

Selection, Optimization, and Validation of 10 Chronic Disease Polygenic Risk Scores for Clinical Implementation in Diverse US Populations

Gene-Based Tests Could Predict Your Odds for Common Illnesses

;