How Genetic Ancestry Redefines Normal Lung Function and Disease Diagnosis

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• Precision Medicine in Lung Function Assessment
• Uncovering Vast Genetic Diversity in Mexico
• The Clinical Impact on Disease Diagnosis
• Implications Beyond Lung Disease
• Understanding Global Genetic Variation
• The Future of Personalized Medicine
• Full Transcript

Precision Medicine in Lung Function Assessment

Dr. Esteban Burchard, MD, a Professor of Pharmacogenomics at UCSF, is a leading voice in the movement toward precision medicine, which aims to treat every patient as a unique individual. His work fundamentally challenges the traditional medical model that applies uniform standards to diagnose lung diseases like asthma and COPD. Dr. Burchard's research shows that an individual's genetic DNA ancestry is a critical factor in establishing their personal "normal" value for lung function, moving beyond outdated population-wide averages.

This shift is crucial because lung function measurements are a cornerstone of respiratory diagnosis. These simple tests, which gauge how much air a person can exhale and how quickly, are used to determine if a patient has a disease. Dr. Esteban Burchard, MD, emphasizes that precision medicine requires adjusting these diagnostic criteria for each person based on their genetic background to ensure accuracy and fairness in their healthcare journey.

Uncovering Vast Genetic Diversity in Mexico

The foundation of this discovery was a major international clinical trial led by Dr. Esteban Burchard, MD, in collaboration with Dr. Carlos Bustamante from Stanford University. Published in the prestigious journal Science, this research focused on studying the genetic ancestry of indigenous populations across Mexico. The team made a startling finding: the genetic diversity among these groups was immense.

Dr. Esteban Burchard, MD, explains that a Native American individual from northwestern Mexico is as genetically different from a Native American in southeastern Mexico as a person of Chinese descent is from a person of European descent. This level of diversity had been largely overlooked in medical research. The team then measured lung function in over 1,000 individuals from these communities and found that genetic ancestry accounted for as much as a 10% difference in results—a variance with profound clinical significance.

The Clinical Impact on Disease Diagnosis

A 10% difference in lung function is not a minor statistical finding; it is a clinically massive shift that can completely alter a patient's diagnosis and life trajectory. Dr. Esteban Burchard, MD, highlights that the equations defining "normal" lung function are used to make critical decisions. This single percentage point can determine whether a person is diagnosed with a debilitating lung disease like COPD or emphysema or is considered healthy.

Furthermore, these criteria govern eligibility for life-altering interventions. Dr. Esteban Burchard, MD, notes that the results are used to qualify patients for lung transplantation, determine disability payments, and authorize oxygen therapy. A miscalculation based on an incorrect "normal" value could therefore deny a sick patient a necessary transplant or disability support, or conversely, subject a healthy individual to unnecessary treatments. This research underscores why a personalized medicine approach is an ethical and medical imperative.

Implications Beyond Lung Disease

The principles of personalized medicine championed by Dr. Burchard extend far beyond respiratory conditions. He provides powerful examples of how genetic ancestry influences the risk of developing other diseases and the probability of experiencing severe medication side effects. For instance, genetic background plays a significant role in an individual's susceptibility to multiple sclerosis.

Another critical example involves the common epilepsy medication carbamazepine (Tegretol). Dr. Esteban Burchard, MD, points out that a person's genetic DNA ancestry can dramatically increase their risk of developing a severe, sometimes fatal, skin reaction to this drug. This illustrates a core benefit of precision medicine: using genetic information to predict adverse drug reactions before a prescription is ever written, thereby enhancing patient safety and optimizing treatment outcomes.

Understanding Global Genetic Variation

The findings from Mexico have global relevance, debunking the myth of genetically homogenous populations anywhere in the world. Dr. Esteban Burchard, MD, explains that Europe, for example, has a significant "genetic gradient" from its northwest to its southeast, shaped by millennia of migration. This means that two individuals both identifying as "European" can have substantial genetic differences that may influence their health.

Dr. Esteban Burchard, MD, and his team replicated their study in African American populations and published the confirming results in the New England Journal of Medicine, reinforcing the universal importance of genetic diversity. Most modern populations are a mixture of several ancestral groups, and as Dr. Burchard's work in Latin America shows—where people are a combination of African, Native American, and European ancestry—this genetic admixture must be accounted for in medical practice to achieve true health equity.

The Future of Personalized Medicine

The work of Dr. Esteban Burchard, MD, paves the way for a future where every medical decision is informed by a deep understanding of a patient's unique genetic identity. The goal is to move completely away from the "one-size-fits-all" model and toward a healthcare system where diagnostics and treatments are meticulously tailored. This approach ensures that a diagnosis of asthma or COPD is not just a label but an accurate reflection of an individual's health status based on their personal normal.

Dr. Anton Titov, MD, the interviewer, underscores that seeking a medical second opinion is a powerful tool for patients. It can confirm that a lung disease diagnosis is correct and complete, and, crucially, that their personal genetic ancestry has been considered. A second opinion helps ensure that the chosen treatment strategy is truly the best personalized medicine approach, giving patients confidence in their care plan and improving their long-term health outcomes.

Full Transcript

Genetic factors can make a difference for suitability for lung transplantation, disability payments, or oxygen therapy. A leading precision medicine expert explains how individual genes affect lung function in asthma and COPD.

Genetic factors in lung disease play an important role in establishing a "normal value" for lung function. There is no "one size fits all" medicine anymore. We have to treat each individual differently. This is the goal of precision medicine—to treat everyone differently.

Research on genetic diversity shows the importance of genetic DNA ancestry in diagnostics. Genetic diversity is important at the individual level.

Dr. Anton Titov, MD: How do genes influence the risk of asthma development? How do genes influence equations of lung function used in disability payments and lung transplantation?

A video interview with a top expert in medical genetics and asthma. A medical second opinion confirms that a lung disease and COPD diagnosis is correct and complete. A medical second opinion ensures that genetic DNA ancestry information is included in the diagnosis of lung disease and COPD. It also helps to choose the best personalized treatment strategy for lung disease and COPD.

Seek a medical second opinion and be confident that your precision medicine treatment is the best.

Dr. Anton Titov, MD: You have recently done a major genetic clinical trial in collaboration with Doctor Carlos Bustamante from Stanford University. This clinical trial showed unexpected results for personalized medicine. This research profoundly influences our approach to the genetics of asthma. It shows the benefits of personalized medicine. It shows how people respond to medications. It also shows how personal genetics influences the risk of side effects from medications.

Dr. Esteban Burchard, MD: Yes. This clinical trial on personalized medicine was published in the most prestigious scientific journal, "Science". Global media also reported your clinical trial results around the world because you have discovered several unexpected findings.

Please tell us about your research on precision medicine. Tell us about its implications for everyone in the world. It shows the power of personalized medicine.

Dr. Esteban Burchard, MD: First of all, thank you. This precision medicine clinical trial is the result of a major international collaboration. We are part of a big team of people. We worked with community healthcare providers and with community leaders. We worked with different government agencies. We worked with different medical institutions around the world and in the United States.

We studied the genetic DNA ancestry of indigenous populations in Mexico. These people in the United States are called Native Americans, but in Mexico they are called indigenous people. It is the population that was there before Columbus arrived in America.

First, we demonstrated that there is a lot of personal genetic diversity among the indigenous population in Mexico. A Native American in northwestern Mexico is as genetically different from a Native American in southeastern Mexico. The difference in DNA is large. It is the same as the difference between a Chinese person's DNA and a European person's DNA.

That was a huge result on its own merit. It's important for precision medicine. But I am a physician-scientist. I am interested in factors of health that are important for practical medicine.

So we measured lung function in indigenous people of Mexico. Lung function is very easy to measure. It is as easy to measure as a person's height or heart function. We asked the question: Does personal genetic DNA ancestry make a difference in the probability of a person getting lung disease?

We included data from Native Americans into the equations to determine if a person meets diagnostic criteria for lung disease. We demonstrated that genetic DNA ancestry makes a difference in diagnostic criteria of lung disease. Genes played a role in as much as 10% of lung function.

This is a very significant result for personalized medicine. It changes clinical criteria for diagnosis of lung disease. It is as if a person became 10 years older if we looked only at lung function.

The difference in lung function could be as large as 10%. This is clinically important. The results of your clinical trial mean that a person may fulfill criteria for diagnosis of lung disease, or the person can be considered healthy. The difference is in what is considered "normal" for such a person.

"Normal" value of lung function usually depends on age. But "normal" value of lung function also depends on personal genetic DNA ancestry of this person. Personalized medicine requires adjustment of diagnostic criteria for each person.

Dr. Esteban Burchard, MD: Yes. This is important because criteria of "normal" lung function mean a lot to patients. These equations of lung function are used to determine eligibility for surgery. "Normal values" are also used to determine disability payments to a patient.

These criteria are also used to qualify patients for lung transplants, for oxygen therapy, and other treatments. A difference of 10% in lung function is large and can change a diagnosis of lung disease of the patient.

Diagnosis of many different diseases—asthma, emphysema—depend upon standards of "normal" lung function. Our important conclusion is that we cannot use a "one size fits all" approach in medicine. We cannot simply say, "Because you are a European, all Europeans are the same as you are."

Dr. Anton Titov, MD: This is a goal of personalized medicine—to tailor diagnosis and treatment for each person.

Your research clinical trial included more than 1,000 people from many regions of Mexico. Your clinical trial conclusions are important for other regions of the world. Northern Europeans are probably very different from Southern Europeans. This is true for other regions.

Some people consider them homogeneous. Sometimes they make diagnostic and treatment decisions in the era of precision medicine.

There is a "genetic gradient" in Europe between northwest and southeast. Many people migrated in Europe between North and South, between East and West. Europeans are not all the same. Understanding personal genetic diversity is key to precision medicine.

We showed the genetic diversity of people in Latin America and in Mexico. People in Mexico are a combination of three major racial groups: African, Native American, and European. We showed that genetic DNA ancestry matters in medical decisions.

Dr. Esteban Burchard, MD: This is a major benefit of personalized medicine. This is a very important finding. We repeated the clinical trial in African Americans and obtained similar results. We published our results in the New England Journal of Medicine. It is one of the most famous medical journals in the world.

Please tell us examples of precision medicine. Sometimes individual genetic DNA ancestry profoundly influences the risk of getting certain diseases. DNA ancestry affects the probability of experiencing side effects from medications.

You showed in your research that genetic DNA ancestry plays an important role in multiple sclerosis. You also showed that genetic DNA ancestry plays a role in the probability of severe side effects from a commonly prescribed epilepsy medication, carbamazepine (Tegretol).

Please tell us more about these two examples because they illustrate the benefits of personalized medicine.

Dr. Esteban Burchard, MD: Yes, this work is a beautiful illustration. Genetic factors in lung disease. How genetic DNA ancestry affects the risk of asthma in adults and in children. "Normal lung function" depends on genetic DNA ancestry.