Genetics, Human Diseases, and Precision Health
Sebastian Zöllner
Professor of Biostatistics and Psychiatry, Co-Director of Precision Health at University of Michigan
Sebastian Zöllner, professor of Biostatistics at the University of Michigan School of Public Health, refers to much of his work as genetic epidemiology—using genetic information to understand more about human disease and alleviate disease burdens.
“Many diseases are hereditary—from heart disease to diabetes to cancer,” Zöllner notes. “And infectious diseases can have a genetic component. We saw this recently with COVID-19, looking at how genetic variations affected the likelihood of symptomatic disease and severity.”
As a biostatistician and genetics expert, and as precision health researcher and leader, Zöllner wants to ensure that the data we collect and the questions we ask of that data will lead to more interdisciplinary collaborations and deeper understandings of how to alleviate human disease and create healthier lives.
Understanding genetic makeup has a whole host of benefits, beginning with diagnostics. “Some people simply have a higher risk of developing a disease like cancer based solely on their genetic profile,” notes Zöllner.
Practitioners use some of this information regularly in clinical settings to improve care. “Today it is standard when diagnosing breast and ovarian cancers to know if a patient has mutations on their BRCA1 and BRCA2 genes, two genes that can protect against tumors when functioning properly and can lead to increased cancer risk if they have a mutation,” Zöllner explains. ”But there is other useful information that we’re not yet using to its full potential.”
When we can see these direct relationships between a patient’s genotype and a particular instance of disease, it can improve prevention and treatment.
Understanding Disease
Along with diagnostics, genetics researchers like Zöllner focus on understanding the processes that cause disease. This led to Zöllner’s interest in psychiatric disease: “At the moment, we continue to identify psychiatric diseases. But our treatments, as good as they are, are based almost entirely on experience, on our observations of patients. Why and how these diseases develop is less well understood.”
Genetics gives us “a peek at the underlying machinery,” Zöllner says, “which can get us closer to why and how these processes are set in motion and closer, hopefully, to better treatment.”
Precision health brings many traditional public health strategies to new levels.
Patients with hereditary high cholesterol, for example, are now often prescribed a PCSK9-inhibitor, “a drug inspired purely by genetics,” Zöllner notes. “We learned that if the gene that controls the PCSK-9 enzyme is overactive, you would be less efficient at removing LDL-cholesterol. Our understanding of this fundamental programming—genetics—led to the development of a treatment that reduces the impact of this gene.”
Using this fundamental genetic knowledge of the “machinery,” Zöllner engages in research projects that pursue precision health solutions to human disease. “Precision health is the attempt to adjust how we treat disease based on a person’s individual characteristics, including but not limited to their genes.”
Zöllner was recently named co-director of Precision Health at the University of Michigan, a cross-disciplinary initiative that combines large datasets with research and practice from public health, medicine, engineering, and many other partner fields not only to improve diagnostic and clinical care but to keep more people from getting sick in the first place.
Precision health brings many traditional public health strategies, like disease surveillance and public service communications, to new levels while also seeking to refine much of how we do clinical care in an ethical manner while also protecting patient privacy. “We need to find ways to go away from the one-size-fits-all care model and instead tailor treatment to individuals whenever that level of data is available.” Precision Health at the University of Michigan brings together researchers from across campus to work on solutions that provide that tailored care.
Nature, Nurture, and Equity
None of this changes the need for great clinical care from a provider, nor the need for great qualitative data. “People have a wide range of genetic variation. We also have a wide range of life experiences. And both have a big effect on how people interact with treatment. Understanding both a person’s genotype and the key biomarkers of their lived experiences through their lives must be brought together for precision health to succeed.”
One example is pharmacogenetics, where pharmacy, medicine, and public health experts examine which drugs work best with different individuals based on their genetic makeup. People can have very different responses to drugs, and genetics typically provides a lot of information for understanding those different responses.”
The ongoing conversation between genetics and environment is where precision health initiatives will have even more significant impacts on public health.
Because we need to understand nature and nurture to understand a person’s health, we need “not only as much genetic data from as many individuals as possible across the entire population but also from as many individuals as possible who represent the range of patient genetic makeup,” says Zöllner.
Precision health is not just about genetics.
A big challenge for precision health—perhaps the biggest challenge to any scientific initiative built around genetic information—might sound familiar: “There are still many socioeconomic and racial biases in the data itself,” Zöllner explains. “This is a particular problem for precision health, because treatments are most easily developed for the type of person most common in the data we have. Due to biases in access to health care and many other factors, individuals of European descent end up being even more common in the data than we would expect due to demography.”
“This needs to change,” Zöllner says, “because existing treatments are already designed for the most predominant patients, so the real benefit of precision health is improving care for those who are not seen as often, whatever that might mean in our data and in our societies. We really need to improve recruiting in minority populations so that this work can realize the benefit of precision health for people that are not as well served by standard approaches.”
Every person who supports these initiatives can increase the quality of future treatment for others—including people in your own communities and thousands of people you’ll never meet. Zöllner says people in precision health work hard on community outreach. “The biggest thing is building and earning trust, and people tend to trust those they know. Trust can mean different things in different communities. So we partner with other medical systems and community leaders to try to improve the data we have.”
More than Genetics
Precision health is not just about genetics, Zöllner points out: “We have researchers using artificial intelligence to understand patient biomarker monitoring in real time.”
Others use precision health techniques to improve interpretation of clinical imaging data. “Anywhere you have lots and lots of tiny bits of information and a research team that wants to ask interdisciplinary questions, you are on your way to precision health answers that can help people stay healthier,” Zöllner says.
“Michigan is really good at going beyond genetics,” Zöllner notes. “Counseling and communication around genetics are vital functions of this field, but we need experts from behavioral science, counseling, and communications to do those things well.”
Zöllner also wants to make sure researchers on campus understand the many services Precision Health at U-M provides. “Any researcher in any field who wants to incorporate genetic analysis into their work—but isn’t quite sure about the details—should get in touch with us.”
The University of Michigan system has over 4 million records from over 80,000 individuals with genetic data. “That number is growing, and we are working hard to increase the diversity of the data. So there are all kinds of projects where you could incorporate that data, all kinds of questions you could pose to that collection and—with the guidance of a genetics analyst on our staff—learn more about human health,” Zöllner says.