JACKSONVILLE, Fla. — Mayo Clinic researchers report encouraging early results from an experimental therapy targeting the genetic cause of a rare form of amyotrophic lateral sclerosis, or ALS. The study is published in Med. 

The single-patient study points to a broader possibility in precision medicine — using the genetic cause of a disease as a framework for testing highly targeted therapies, particularly for patients with rare conditions that have few treatment options. 

"I didn't think I would see this kind of research in my lifetime — identifying a disease-causing mutation, developing an experimental therapy and delivering it to a patient," says Björn Oskarsson, M.D., a Mayo Clinic neurologist and senior author of the study. "It speaks to the power of science and how far genetically targeted treatments have come." 

Targeting genetic ALS

That work builds on a long history of ALS genetics research at Mayo Clinic. In 2011, then-Mayo Clinic neurogeneticist Rosa Rademakers, Ph.D., and colleagues helped discover a mutation in the C9orf72 gene, now recognized as the most common inherited genetic cause of ALS. Dr. Rademakers received the 2026 Breakthrough Prize in Life Sciences for her role in the discovery. Mayo researchers also developed early models that helped scientists investigate how the mutation contributes to ALS.

Since joining Mayo, Dr. Oskarsson has helped translate advances in ALS genetics into treatment research, contributing to the first approved treatment of genetic ALS. 

ALS progressively damages motor neurons, the nerve cells that control voluntary movement. In this study, genetic testing identified a mutation in CHCHD10, a gene associated with a rare form of ALS. The mutation appears to make the CHCHD10 protein harmful to nerve cells and is linked to abnormal changes in TDP-43, a protein closely associated with ALS. 

Mayo researchers collaborated with the nonprofit n-Lorem Foundation, which develops medicines based on antisense oligonucleotides, or ASOs, for people with ultrarare genetic diseases. ASOs are short synthetic strands of genetic material designed to bind to RNA and reduce production of a protein that contributes to disease. The foundation developed and evaluated more than 320 ASOs targeting CHCHD10 before selecting a lead candidate based on specificity and early safety testing. 

Early signs of treatment response

The study reports on the patient's first six doses of the experimental ASO, delivered through injections into the fluid surrounding the spinal cord. Treatment was well tolerated, and levels of neurofilament light — a blood biomarker of nerve-cell injury — declined by as much as 50%. Measures of breathing, cognition and physical function remained stable or showed modest improvement. 

"The quick response in neurofilament light was very encouraging," Dr. Oskarsson says. In a progressive disease such as ALS, he adds, stabilization can be a meaningful observation. 

The study also gives researchers a chance to look more closely at what is happening inside cells during the therapy. Using samples collected before and during the delivery of the ASOs, the team is studying changes in TDP-43 as well as mitochondrial function and gene activity. The goal is to understand how suppressing CHCHD10 may affect the disease process at a molecular level. 

The therapy remains experimental research and is not standard clinical care. Dr. Oskarsson estimates that about 50% of ALS is genetic, but he notes that only a subset of those cases are currently suited to an antisense approach. Some genetic forms may require other strategies, including gene editing. 

A framework for precision

The study is part of a broader effort through Mayo Clinic's N-of-1 Therapeutics Program to learn which elements of drug development, clinical evaluation and monitoring can be applied across individualized genetic therapies. 

"Cases like this are how we get started," says Margot Cousin, Ph.D., director of the N-of-1 Therapeutics Program and lead author of the study. "They help us build the scientific, clinical, translational and regulatory framework to do this rigorously and equitably. As we learn how to scale these approaches, the impact could reach far beyond ultrarare disease." 

Research in ultrarare diseases can help establish safety benchmarks, refine genetic-treatment platforms and clarify which disease mechanisms are most amenable to targeted therapy. Those lessons could ultimately inform new approaches to more common diseases. 

For a complete list of authors, disclosures and funding, review the study. 

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About Mayo Clinic 
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.  

Media contact: 

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu 

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Mayo Clinic findings also link specific gut bacteria to cancer survival and identify a pretreatment signal associated with chemotherapy toxicity

ROCHESTER, Minn. — Mayo Clinic researchers have discovered distinct gut microbiome patterns in adults age 50 or younger with colorectal and breast cancers compared with those diagnosed later in life — one of several findings from an analysis of stool samples from 1,364 patients with cancer across cancer types, stages and treatments.

Among younger patients, those with colorectal cancer had higher lactate levels and more Veillonella parvula, a gut bacterium that feeds on lactate. Early-onset breast cancer showed changes across 64 bacterial species and lower levels of primary bile acids.

Published in Cell, the findings come from the Mayo Clinic Cancer Microbiome cohort, a real-world study that recruited cancer patients at Mayo Clinic in Arizona, Florida and Minnesota, representing 40 states. Stool samples were collected before patients began a new treatment regimen and linked to detailed clinical data on side effects and outcomes. The samples provided a window into the gut microbiome — the trillions of microbes living in the digestive tract.

Cancer-specific microbiome patterns emerge

Researchers first compared patients with cancer with 287 people without cancer to identify broad microbiome differences. Comparisons across cancer types then revealed more specific signals. After accounting for other health conditions, researchers pinpointed 341 bacterial species associated with five cancer groups.

Among those groups, neuroendocrine tumors showed a broad loss of common, health-associated gut bacteria. Liver and intrahepatic bile duct cancers had higher levels of several bacteria, including Enterococcus faecalis, while esophageal cancer had higher levels of six species, including several Streptococcus bacteria. Distinct associations were also found in lymphoid leukemia and multiple myeloma and related plasma cell cancers.

Distinct patterns in early-onset cancers 

The findings come as colorectal and breast cancer rates rise among younger adults. Colorectal cancer incidence is increasing about 3% a year among adults ages 20 to 49, while breast cancer incidence is rising 1.4% a year among women younger than 50, according to the American Cancer Society.

The colorectal finding raises questions about a possible biological connection: Tumors can produce high levels of lactate, which Veillonella parvula uses to grow. Whether that relationship plays a role in early-onset disease is not yet known.

In breast cancer, one of the 64 species that differed in younger patients was Clostridium scindens, a bacterium involved in bile acid and steroid metabolism.

No comparable age-related microbiome differences were found in brain cancer, the third cancer examined in the early-onset analysis. The colorectal and breast cancer findings do not establish that these microbial or metabolic differences cause early-onset disease, but they identify associations that warrant further study.

Gut microbiome linked to survival and treatment side effects 

Researchers also identified specific gut bacteria associated with survival in colorectal, liver and intrahepatic bile duct, melanoma, ovarian and prostate cancers. In liver and intrahepatic bile duct cancer, Bifidobacterium longum was associated with longer survival and Blautia A massiliensis with shorter survival.

Researchers also studied whether the gut microbiome before treatment was associated with diarrhea during chemotherapy, a side effect that can make treatment harder to tolerate. Among patients receiving 5-fluorouracil, or 5-FU, a chemotherapy used to treat many types of cancer, those who later developed diarrhea had lower levels of bacterial genes capable of breaking down the drug. Much of that function came from Anaerostipes hadrus, a common gut bacterium.

The same signal was not linked to diarrhea in patients receiving carboplatin, another chemotherapy drug, suggesting the finding was specific to 5-FU.

"The microbiome is not the sole driver of cancer or treatment outcomes, but it is an underappreciated component that has not traditionally been considered in therapeutic approaches," says senior author Purna Kashyap, M.B.B.S., a gastroenterologist, director of the Mayo Clinic Microbiome Program and Bernard and Edith Waterman Director, Microbiomics Program, Mayo Clinic Center for Individualized Medicine.. "This gives us a proof of concept that we can begin to understand why some patients experience a particular side effect and identify a target that could potentially be acted upon."

Next, researchers will investigate whether cancer-specific microbial signals play a causal role in disease and validate the microbiome's potential to predict treatment side effects in larger patient groups.

The research was supported in part by the National Institutes of Health and philanthropic gifts from the Valhalla Foundation, the Maxine & Jack Zarrow Family Foundation, and other benefactors to the Mayo Clinic Microbiome Program and Center for Individualized Medicine.

Jun Chen, Ph.D., professor of biostatistics and consultant in Mayo Clinic’s Division of Computational Biology, is also a co-corresponding author. For a complete list of authors, disclosures and funding, review the study. 

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About Mayo Clinic  
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.  

Media contact:   

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu 

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Helix to generate clinical whole genome sequencing and multi-omics data from one million biospecimens, advancing precision medicine as the standard of care

ROCHESTER, Minn. and SAN MATEO, Calif. — Precure, LLC today announced the selection of Helix as its multi-omic laboratory and AI tools provider supporting plans to generate comprehensive molecular data from approximately one million biospecimens and accelerate the integration of molecular insights into routine clinical care at Mayo Clinic and across health systems more broadly.

Less than a week ago, Mayo Clinic announced the launch of Precure, LLC, with founding partner Thermo Fisher Scientific, to help transform how the life sciences community understands the biological changes that occur as disease develops before symptoms occur. Precure, LLC brings together clinical expertise, de-identified longitudinal health information and population-scale molecular data to accelerate the development of new approaches to care.

Helix will provide both advanced AI tools for delivery of genomics into the clinic and biomarker driven research, and population scale multi-omic capability that encompasses clinical whole genome sequencing (WGS) and research grade proteome sequencing. Linked with longitudinal clinical information and high performance compute infrastructure, the objective is to create new opportunities for prevention, diagnosis and treatment.

“Our goal is to generate genomic information that can help inform patient care while creating a powerful resource for discovery,” said Aaron Mangold, M.D., chief medical officer, Precure, LLC. “We are working to make clinical whole genome sequencing and multi-omics a foundation of care, helping us detect disease sooner and act earlier.”

Building on prior work which utilized Helix’s Exome+ ^® sequencing technology, Precure, LLC extends that collaboration by leveraging Helix's experience providing workflow orchestration, (CLIA/CAP) genomic sequencing, data infrastructure, and AI tools to its health system partners. Precure, LLC and Helix have selected Ultima Genomics’ UG200™ Ultra Sequencing Platform as part of the program’s large-scale multi-omics initiative. Helix will use a fleet of Ultima’s next-generation platforms to generate high-quality genomic data for WGS and read-out for proteomics at scale.

“The genome is becoming an enduring patient resource, providing a precision baseline for a lifetime of care,” said James Lu, M.D., Ph.D., CEO of Helix. “Helix brings together the laboratory and data capabilities to make this possible at scale.”

Mayo Clinic's involvement in Precure, LLC is intended to advance its nonprofit mission. Any financial returns to Mayo Clinic would be reinvested in its mission of patient care, research and education. Visit mayo.edu/research/precure for more information.

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About Precure, LLC
Precure, LLC is a Mayo Clinic-controlled company established to generate and responsibly integrate population-scale molecular data with longitudinal clinical information. Precure, LLC creates the infrastructure and scale needed to enable external collaborations, disease-focused discovery and the development of new diagnostics, therapeutics and other healthcare solutions. It complements Mayo Clinic’s investigator-led research and clinical translation activities.

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.  

About Helix
Helix is an enterprise genomics company connecting clinical care and discovery. Its platform brings together clinical sequencing, integration of genomic information into healthcare, and research tools built on linked genomic and longitudinal clinical data. Through its health system partnerships, the Helix Research Network and GenoSphere, Helix helps healthcare and life sciences organizations apply genomics to patient care and the development of new diagnostics and treatments. Learn more at www.helix.com.

Media contacts:

• Tom Millikin, Mayo Clinic Communications, newsbureau@mayo.edu
• Caty Reid, Helix, helix@highwirepr.com

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ROCHESTER, Minn. — A liver disease affecting nearly 30% of adults worldwide is not a single illness but five biologically distinct subtypes, Mayo Clinic researchers have found. Each carries different risks for heart disease, liver failure, cancer and the need for liver transplantation.

The study, published in Nature Communications and conducted in collaboration with scientists at Virginia Tech, shows that metabolic dysfunction-associated steatotic liver disease has multiple pathways — some tied to obesity and diabetes, others driven by inherited genetic factors.

Notably, genetic subtypes are associated with a higher risk of progression to advanced liver disease, including in patients without typical metabolic risk factors.

The findings could help identify high-risk patients earlier and guide more precise screening and personalized treatment.

"When clinical and genomic data are analyzed together at this scale, you begin to see patterns of disease progression that would otherwise remain hidden," says Shulan Tian, Ph.D., co-senior author and a bioinformatician at Mayo Clinic. "Once you separate these subtypes, you can start to match treatments to the biology that's actually driving the disease."

Metabolic dysfunction-associated steatotic liver disease, formerly called nonalcoholic fatty liver disease, occurs when fat builds up in the liver. It often develops without symptoms but can progress to inflammation, scarring and irreversible damage. It is a leading cause of cirrhosis, liver cancer and transplantation worldwide.

Decoding liver disease at scale

To uncover these subtypes, researchers integrated genetic sequencing with detailed clinical data from more than 4,600 patients with the disease. The dataset spanned a wide range of measures — from liver enzymes, body mass index and lipid levels to coexisting conditions such as diabetes, depression and sleep apnea.

Using advanced computational modeling, the team identified groups of patients who shared underlying biological signals, defining distinct subtypes of the disease.

"What's emerging here is a way to systematically identify meaningful subgroups within complex disease," says Eric Klee, Ph.D., co-senior author and the Everett J. and Jane M. Hauck Midwest Associate Director of Research and Innovation. "It helps us map complex disease with such precision that we can begin to anticipate its course and intervene before the most serious damage occurs."

The discovery was powered by Mayo Clinic's Research Data Atlas, a platform that connects genetic data with patient records to reveal patterns across large populations — a system Dr. Klee helped build. A key component of the Atlas is the Tapestry Study, which has generated Mayo Clinic's largest collection of exome data from more than 100,000 participants. The dataset captures key genetic information that shapes how diseases develop and progress.

"This is exactly the kind of insight large-scale genomic research was built to deliver," says Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director for the Center for Individualized Medicine who led the Tapestry Study and is a co-author of the research. "When you connect genetic data with detailed clinical information across large populations, you can start to redefine diseases in ways that directly impact patient care."

Liver disease's hidden effects across the body

The study also revealed links beyond the liver. For the first time, researchers found that specific subtypes are associated with conditions such as depression, sleep apnea and migraine, underscoring the disease's broad systemic impact across multiple organ systems.

Next, the team plans to test the approach in broader patient populations and explore how these subtypes respond to different treatments, including therapies such as GLP-1 receptor agonists.

First author Tahmina Sultana Priya, now a Ph.D. student at Virginia Tech, contributed to the research while at Mayo Clinic. For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:  

• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu

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ROCHESTER, Minn. — Mayo Clinic researchers have discovered that chemical signals produced by gut bacteria work together to control intestinal movement. One bacterial signal helps set the intestines in motion, while another primes gut cells to respond more strongly, amplifying the effect.

The research expands scientists' understanding of how the gut microbiome communicates with the body, moving beyond the traditional focus on individual bacteria or bacterial molecules.

The findings, published in the Proceedings of the National Academy of Sciences, point to a potential new direction for microbiome-based treatments: restoring combinations of microbial signals rather than targeting a single microbe or molecule. The strategy could have implications for constipation-predominant irritable bowel syndrome, a chronic condition marked by abdominal pain and constipation.

"The gut microbiome is made up of trillions of microbes producing a vast array of chemical messages that interact with cells throughout the digestive tract," says Purna Kashyap, M.B.B.S., a Mayo Clinic gastroenterologist, director of the Mayo Clinic Microbiomics Program and a senior author of the study. "Deciphering how those signals work in combination gives us a much more precise picture of what is disrupted in disease and what would need to be restored to recover normal function."

How bacterial signals work in combination

Researchers focused on two bacterial molecules: hypoxanthine and butyrate. Earlier Mayo Clinic research found lower levels of both in patients with constipation-predominant irritable bowel syndrome. That finding led researchers to a deeper question: How do these molecules affect intestinal movement?

In the new study, the researchers found that hypoxanthine prompts specialized cells lining the intestine to release serotonin, a chemical messenger that helps move food through the digestive tract. Butyrate works differently. It primes the cells to respond more strongly to hypoxanthine, amplifying the effect.

These specialized cells, called enterochromaffin cells, serve as hubs where different microbial signals come together. They help the gut receive and respond to multiple chemical messages at once.

Researchers followed that chain of events from what happens inside a single gut cell to how contents move through the intestines. They used laboratory-grown intestinal cells, miniature gut models called organoids, intestinal tissue and genetically altered bacteria to piece together each part of the process.

Gianrico Farrugia, M.D., president and CEO of Mayo Clinic and a co-author of the study, is a gastroenterologist whose research has focused on the mechanisms that control gastrointestinal function.

"We have an opportunity to move beyond managing the consequences of disease and toward restoring function for patients," Dr. Farrugia says. "That starts with answering the unanswered questions we see in our patients and following the biology until we understand the mechanism. With that depth of understanding, we can uncover new possibilities for treatment and ultimately advance new cures."

What's next 

Researchers next want to determine whether identifying combinations of microbial signals that are altered in individual patients could eventually help guide treatment. Future research will explore whether restoring complementary signals can improve intestinal movement, with the longer-term goal of developing more precisely targeted microbiome-based therapies.

The research was supported by the National Institutes of Health, Mayo Clinic Center for Individualized Medicine, Mayo Clinic Microbiome Program and other organizations. One or more of the investigators is an inventor of technology related to this research. For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic  
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.  

Media contact:   

• Sharon Theimer, Mayo Clinic Communications, newsbureau@mayo.edu

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Mayo Clinic researchers are uncovering the earliest shifts in disease biology — long before symptoms appear — revealing how disease takes root and opening new possibilities to change its course. 

By the time a disease is diagnosed, it may have been developing silently for years. Along the way, the body leaves clues: proteins shift, metabolism changes, immune responses evolve, and environmental exposures leave measurable traces. Until recently, many of these early signals were impossible to detect.

Mayo Clinic researchers are now charting that hidden period between health and disease — a new frontier in medicine that could transform how conditions such as Alzheimer's disease, heart failure, pulmonary fibrosis, chronic liver disease and chronic kidney disease are identified and intercepted before symptoms emerge.

The new Mayo Clinic initiative, called Precure Research, brings together biospecimens, advanced biological data, environmental health research, longitudinal clinical data, wearable technologies and artificial intelligence (AI) to better understand how disease begins, predict risk earlier and create new opportunities for prevention.  

"Precure Research marks the beginning of the next era of scientific discovery and its translation into patient care."

Dr. Konstantinos Lazaridis

A glimpse of what's possible 

The initiative is already generating discoveries. Mayo Clinic scientists have identified inherited risks for cancer and cardiovascular disease in nearly 2,000 people — many of whom had no previous indication they were at risk. Other studies have shown that certain precancerous changes can be detected years before cancer develops. AI can help clinicians identify signs of pancreatic cancer years before diagnosis, while subtle biological changes linked to Alzheimer's disease begin decades before memory loss. Mayo Clinic researchers are using AI, genetics and wearable technologies to reveal inherited heart disease before heart failure.

"Precure Research marks the beginning of the next era of scientific discovery and its translation into patient care," says Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director of Mayo Clinic's Center for Individualized Medicine and director of Precure Research. "We are building the analytical and clinical tools needed to investigate questions that medicine has long recognized but has not been able to fully answer in ways that directly benefit patients."

The invisible years before diagnosis 

The initiative combines data from genes, proteins, metabolites, clinical records, wearable devices and environmental exposures to create a comprehensive view of how health changes and disease develops over time.

Underlying Precure Research is a new Mayo Clinic research ecosystem designed to study health and disease at an unprecedented scale. The initiative aims to build Mayo Clinic's largest integrated collection of biospecimens and scientific and health data to accelerate disease prediction and prevention.

Biological samples become data, and data becomes insight into the mechanisms of disease. Those insights drive the discovery of new biomarkers and therapies while informing smarter clinical trials.

AI helps researchers power that transformation, analyzing billions of data points simultaneously to reveal patterns that would otherwise remain invisible.

"Genomics showed us the blueprint, the underlying architecture of human biology," Dr. Lazaridis says. "Now we're watching that structure in motion — shifting, adapting, unfolding over time, shaped by the world around us and inside us, ultimately influencing the unique lives we each live." 

A lifetime of exposures

Disease is shaped by more than genetics alone. Across a lifetime, environmental and lifestyle exposures leave biological changes that accumulate over time. Scientists call this the exposome: the sum of those exposures and their effects on human biology.

These influences range from air, water and diet to pollutants, heavy metals, pesticides, physical activity, sleep, stress, noise and light.

"The air we breathe, the food we eat and the places we live leave a biological imprint," Dr. Lazaridis says. "Understanding those accumulated influences is essential to understanding why disease develops in one person and not another."

Researchers can now measure many of these exposures directly in blood and other biospecimens. Early efforts focus on heavy metals, pesticides and microplastics, linking those findings with geographic data to better understand how the places people live may influence their long-term health.

The exposome also captures protective influences, including nutrients and bioactive compounds that may support resilience and regulate inflammation, aging and metabolism.

A new vision for medicine 

The initial focus of Precure Research includes diseases of the brain, heart, kidneys, liver, and lungs, and their intersection with biological pathways such as inflammation, oxidative stress, aging and metabolic dysfunction.

Its long-term aim is to extend healthspan — the number of years people live in good health, free from chronic disease and disability — by addressing the drivers of chronic disease.

Precure Research is part of Mayo Clinic's Bold. Forward. strategy to Cure, Connect and Transform healthcare — helping define a future where disease is identified earlier, understood more completely and intercepted before it takes hold.

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PHOENIX — Researchers have validated a genetic scoring tool that may help physicians diagnose idiopathic pulmonary fibrosis and identify which patients are at greatest risk for severe outcomes, including death or the need for a lung transplant. The findings come from a new international study of more than 570,000 people co-led by Mayo Clinic and Brigham and Women's Hospital.

Published in the American Journal of Respiratory and Critical Care Medicine, the study is one of the largest real-world evaluations of a polygenic risk score for idiopathic pulmonary fibrosis. The findings bring this genomic approach one step closer to clinical care.

"Polygenic risk scores add a new layer of biological insight into the prediction of pulmonary fibrosis and mortality outcomes, bringing us closer to a future where diagnosis, prognosis and treatment are informed by each patient's unique molecular signatures."

- Dr. Victor Ortega

Researchers analyzed genomic and electronic health record data from four major biobanks in the U.S. and U.K., including the Mayo Clinic Biobank and Mayo Clinic Tapestry. They calculated a polygenic risk score for each participant by combining the effects of more than 60,000 DNA variants associated with idiopathic pulmonary fibrosis. While each genetic variant contributes only a small amount of risk, together they reveal patterns of inherited susceptibility that would otherwise be difficult to detect.

The researchers then tested whether the score could identify patients with the disease and predict clinical outcomes.

People with high polygenic risk scores were nearly three times more likely to have the disease than those with lower scores. The genetic score became even more predictive as researchers applied increasingly specific definitions of the disease, suggesting the score may one day help distinguish idiopathic pulmonary fibrosis from other forms of interstitial lung disease.

Among patients with the disease, those with high genetic risk were 23% more likely to die or require a lung transplant, indicating the score may also help identify patients at greatest risk of poor outcomes.

"Every patient has a unique genetic blueprint that we can use to estimate risk for the development of disease," says Victor Ortega, M.D., Ph.D., a pulmonologist, associate director of Mayo Clinic's Center for Individualized Medicine in Arizona, and a co-senior author of the study. "Polygenic risk scores add a new layer of biological insight into the prediction of pulmonary fibrosis and mortality outcomes, bringing us closer to a future where diagnosis, prognosis and treatment are informed by each patient's unique molecular signatures."

"Showing that this approach works across more than half a million people receiving routine clinical care is an important step toward understanding how it can ultimately benefit patients."

- Dr. Christopher Grilli

Idiopathic pulmonary fibrosis causes irreversible scarring of the lungs that progressively limits a person's ability to breathe. More than 100,000 Americans are living with the disease, and an estimated 30,000 to 40,000 new cases are diagnosed each year, according to the National Institutes of Health.

Because its symptoms often resemble those of other interstitial lung diseases, diagnosis can be delayed until significant, irreversible lung damage has already occurred. Confirming the diagnosis sometimes requires an invasive lung biopsy to collect lung tissue. Researchers hope a noninvasive genetic test using DNA from a blood or saliva sample may help reduce the need for those procedures in selected patients.

"Most polygenic risk scores are developed in carefully selected research populations," says Christopher Grilli, Pharm.D., a researcher at Mayo Clinic's Center for Individualized Medicine and co-first author of the study. "Showing that this approach also works across more than half a million people receiving routine clinical care is an important step toward understanding how it can ultimately benefit patients."

If further validated, researchers envision genomic risk scores complementing imaging and other diagnostic tools to help physicians diagnose the disease with greater confidence.

This research aligns with Mayo Clinic's Precure Research initiative, which seeks to uncover the earliest biological changes associated with disease and translate those discoveries into clinical tools that improve diagnosis, personalize care and ultimately change the course of disease. As part of that effort, the Precure-Lung study, led by Dr. Ortega, is expanding Mayo Clinic's research into interstitial lung diseases, including idiopathic pulmonary fibrosis.

For a complete list of authors, disclosures and funding, review the study. 

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About Mayo Clinic 
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news. 

Media contact:  

• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu

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ROCHESTER, Minn. — A new Mayo Clinic study shows that integrating telomere length evaluation and genetic testing into pulmonary care can significantly change how physicians diagnose and treat pulmonary fibrosis — in some cases even redirecting the course of care.

Telomeres are protective caps at the ends of chromosomes — the structures that carry a person's DNA. They naturally shorten as people age, but in some inherited conditions, they become unusually short. This shortening has been linked to certain forms of pulmonary fibrosis, a group of diseases that cause progressive scarring in the lungs and make breathing increasingly difficult.

In the study of 66 patients, nearly 1 in 5 had a disease-causing genetic variant, and results from testing changed clinical care in more than half of patients. The results were published in Mayo Clinic Proceedings.

"These diseases are often difficult to diagnose, and patients may be treated based on incomplete or unclear underlying causes," says Kathryn del Valle, M.D., a Mayo Clinic pulmonologist and lead author of the study.

To address this challenge, researchers paired genetic testing with telomere length measurement. Together, these tools helped uncover hidden drivers of disease and guide more precise management decisions.

"This work demonstrates a practical, scalable way to incorporate genetic and telomere assessment into clinical care for patients with fibrotic interstitial lung disease," says Eva Carmona, M.D., Ph.D., a Mayo Clinic pulmonologist and senior author.

The additional insights from testing led to meaningful changes in care, including the evaluation of comorbidities, medication adjustments, referrals to specialized clinics and earlier consideration of lung transplant. The information can also help clinicians avoid treatments and procedures that may be ineffective — or even harmful — in patients with certain genetic or telomere-related conditions.

"Genetic and telomere testing may help elucidate why disease is occurring, guide management decisions and identify family members who may be at risk," Dr. Carmona says.

Beyond individual patients, the findings have important implications for families. Identifying a genetic cause can help flag relatives who may be at risk, allowing them to pursue earlier screening, genetic counseling and testing.

Mayo Clinic plans to expand this model and launch a Familial Pulmonary Fibrosis Clinic to further coordinate genetic testing, counseling and comprehensive care for patients and at-risk relatives.

For a complete list of authors, disclosures and funding, review the study. 

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and to providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu

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A new era of medicine is emerging at Mayo Clinic — one that finds disease before symptoms appear 

ROCHESTER, Minn. — When Mayo Clinic researchers sequenced the genomes of 484 seemingly healthy adults, they found that about 13% carried a serious, previously unrecognized genomic risk — conditions those patients did not know about and that standard care would likely miss.

Nearly all participants, 98.6%, had at least one genetic finding, and for most, the results called for monitoring. The study, published in Genetics in Medicine, also takes a closer look at what it takes to turn those findings into the proper follow-up care.

Among the 13%, the actionable findings pointed to serious risks, including hereditary breast and ovarian cancer; Lynch syndrome, linked to colorectal cancer; cardiomyopathy; long QT syndrome; and amyloidosis.

"These are people traditional testing based on symptoms or family history would not identify," says Dr. Konstantinos Lazaridis, the Carlson and Nelson Endowed Executive Director of the Center for Individualized Medicine and senior author of the study. "This study helps define the blueprint for integrating genomic insight into care at scale — turning information into decisions that can change the trajectory of disease."

From discovery to care

Identifying the risk, it turns out, is the easiest part. Acting on it is far more complex. Nearly every case required clinical interpretation, documentation and communication. This work fell largely to genetic counselors, who reviewed results, prepared individualized summaries and helped guide next steps for patients and care teams.

"Genetic counselors are often the first people to share this kind of information with patients," says Jessa Bidwell, a certified research genetic counselor and first author of the study. "There can be surprise, anxiety, devastation, and at times relief at finally having an explanation. Our role is to meet people in that moment and help them understand what their health risks might be, based on the genetic finding, and their personal and family history."

Most participants with actionable findings followed through, completing referrals and connecting with primary care specialists. Yet fewer than half had a documented conversation with a primary care professional after receiving results — underscoring how difficult it remains to integrate genomic findings into routine care.

The study positions predictive genomic screening as both a clinical opportunity and a systems challenge. The science exists. Researchers and clinicians are still building the infrastructure to act on it consistently.

At Mayo Clinic, that infrastructure is beginning to take shape through an initiative called Precure. Genomic screening is one part of that initiative, which aims to detect disease earlier by combining genetic data with other biological signals.

"Precure is one example of a moonshot for human health at Mayo Clinic," says Dr. Lazaridis, who leads the initiative. "It reflects Mayo Clinic's commitment to move medicine beyond treatment and toward lasting wellness." - Dr. Lazaridis

Predicting disease before it begins 

Most diseases don't arrive without warning. They begin with small shifts in genes, molecules, proteins and immune signals that develop over time, often years before symptoms appear.

Precure is Mayo Clinic's enterprise-wide effort to detect those early signals and intervene sooner. Powered by advanced computing and artificial intelligence (AI), the initiative currently focuses on five organ systems — the brain, heart, kidneys, liver and lungs — studying conditions such as Alzheimer's disease, heart failure and chronic liver disease to better understand how they emerge and progress.

The work draws on expertise from across Mayo Clinic and is supported by Mayo Clinic Platform, which brings together large-scale patient data and advanced computing to enable scientists to study disease across populations.

"Precure is one example of a moonshot for human health at Mayo Clinic," says Dr. Lazaridis, who leads the initiative. "It reflects Mayo Clinic's commitment to move medicine beyond treatment and toward lasting wellness."

Precure is part of Mayo Clinic's Bold. Forward. strategy to Cure, Connect and Transform healthcare. The genomic screening study is an early demonstration of what that looks like in practice: science that doesn't wait for disease to announce itself, and a system already being built to act on what it finds.

For a complete list of authors, disclosures and funding information, review the study. 

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

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Dr. Adam Jacob has spent his career keeping patients safe in the operating room. As a Mayo Clinic anesthesiologist, he closely monitors every heartbeat and breath, adjusting anesthesia and responding to subtle changes in the body during surgery.

Watch: Mayo Clinic uses DNA screening to prevent life-threatening reactions during anesthesia

Journalists: Broadcast-quality video (3:31) is in the downloads at the end of this post. Please courtesy: "Mayo Clinic News Network." Read the script.

But one risk does not appear on monitors or in a patient's medical history: malignant hyperthermia. The rare, inherited condition can be triggered by certain anesthesia drugs, causing rapid muscle breakdown and a dangerous rise in body temperature.

Without prompt treatment, it can be fatal. Anesthesia teams are trained to recognize malignant hyperthermia, and a lifesaving antidote is kept in every location where anesthesia is administered. 

The risk is written into a person's DNA. 

An unexpected discovery

Until recently, Dr. Jacob did not know he carried that genetic risk. Like many people with malignant hyperthermia susceptibility, he had undergone anesthesia before without incident — the reaction is only triggered by certain drugs. 

"I had no symptoms, no family history and no reason to suspect anything," Dr. Jacob says. "If I hadn't been part of a research study, my first sign could have been an emergency in the operating room." 

An estimated 1 in 2,000 to 3,000 people carry genetic susceptibility to malignant hyperthermia, most without knowing it. Actual reactions are less common and can be prevented when the risk is identified in advance. 

More than a decade ago, Dr. Jacob donated his DNA as part of a Mayo Clinic research study, with no expectation the data would ever circle back to him personally. 

Recent advances in genomics changed that. Through a new study, Dr. Jacob received a letter from Mayo Clinic, followed by a call with a genetic counselor. He learned he carries a variant in RYR1, the gene most commonly linked to malignant hyperthermia. 

Because the condition is hereditary, Dr. Jacob had his two teenage sons tested. Both carry the same variant. Their medical records were updated to guide future anesthesia care, and they now wear medical ID bracelets. 

Dr. Jacob's wife, Kelly Jacob, is a nurse anesthetist, underscoring that even families deeply familiar with anesthesia care can carry this risk without knowing it. 

Dr. Jacob's experience also shows how identifying risks in one person can help protect an entire family. 

Identifying risk before the operating room 

The effort to understand the prevalence of malignant hyperthermia susceptibility is led by Dr. Timothy Curry, a Mayo Clinic anesthesiologist and physician-scientist, and one of Dr. Jacob's longtime colleagues. 

Dr. Curry studies genetic risk at scale through Mayo Clinic's Research Data Atlas, a research platform that connects genomic data with clinical records across the institution. In an analysis of nearly 150,000 individuals, he identified 134 people with variants linked to malignant hyperthermia susceptibility, most of whom were previously unaware 

"Traditionally, malignant hyperthermia declares itself in the operating room. By starting with genetics, we're able to find the risk long before that moment, and that opens the door to prevention rather than reaction."  - Dr. Timothy Curry

The two physicians trained together early in their careers. When Dr. Curry realized that Dr. Jacob was among those identified, the work became personal, he says. 

Dr. Curry's goal is to identify people with previously unrecognized malignant hyperthermia risk before they ever need anesthesia. That early knowledge matters because anesthesia drugs linked to malignant hyperthermia remain essential in emergencies, including trauma cases or when clinicians must quickly secure a patient's airway. 

"Traditionally, malignant hyperthermia declares itself in the operating room," Dr. Curry says. "By starting with genetics, we're able to find the risk long before that moment, and that opens the door to prevention rather than reaction." 

In parallel, Dr. Curry and his team are reviewing medical records for the people identified to see whether any experienced anesthesia reactions before the risk was known. 

Turning genetic findings into clinical guidance 

Identifying genetic risk is only the first step. Making sure it informs care requires ongoing education for providers, patients and families. 

That work involves Dr. Filippo Pinto e Vairo, medical director of Mayo Clinic's Program for Rare and Undiagnosed Diseases, along with a team of genetic counselors. When a potential genetic risk is identified, this team works with patients and families to confirm the finding and explain what it means for their care. The result is then integrated into the medical record so anesthesia teams can plan future care and avoid triggering drugs. 

"This is an extraordinary time in genomics. At Mayo Clinic, we're increasingly integrating genomics into clinical care at scale, and it's changing what's possible across healthcare." - Dr. Pinto e Vairo

That same approach extends beyond malignant hyperthermia. Dr. Pinto e Vairo and the team apply it to a growing range of genetic findings that can meaningfully change care. 

"This is an extraordinary time in genomics," Dr. Pinto e Vairo says. "At Mayo Clinic, we're increasingly integrating genomics into clinical care at scale, and it's changing what's possible across healthcare." 

In addition to malignant hyperthermia, Mayo Clinic researchers are returning genetic results linked to hereditary cancers, heart disease, metabolic diseases and other risks where early knowledge can guide care. 

From reaction to prevention

Genetic testing for malignant hyperthermia risk is now incorporated into Mayo Clinic's preoperative care pathways, shifting anesthesia care from reaction to prevention. 

For Dr. Jacob and his family, that shift transformed a hidden, life-threatening risk into one that can be anticipated, planned for and prevented. 

"This knowledge gives us peace of mind, and a way forward," Dr. Jacob says.

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