The intersection of public health genetics and the environment on Alzheimer’s disease risk


What role does genetics play in disease risk? Can social and environmental factors have an impact on prevention and delaying the onset of a disease? These are the kinds of questions Diane Xue aims to answer as a Ph.D. candidate in the Institute for Public Health Genetics program at the University of Washington School of Public Health (UW SPH). 

“Many universities have human genetics and medical genetics programs, but IPHG focuses on bringing a public health perspective to genetics research,” Xue said. “I really wanted to study at an institution that prioritizes how research actually affects people.” 

In this Q&A, Xue describes why she chose UW SPH for graduate school, her research on Alzheimer’s disease risk and the impact she hopes it will have, and how we improve health equity when it comes to public health genetics.  


What first drew you to public health and why do you enjoy studying it?   

I studied development economics and genetics when I was an undergraduate student at the University of Wisconsin-Madison, and I realized that public health is an interesting intersection and application of those fields. I became fascinated by how health outcomes are shaped by biological versus social factors. I had great learning opportunities throughout college that cemented my view that everything is related to public health. I love that studying and working in public health involves individuals across different fields with a variety of skills all working in to shift distributions of health.    

Why did you decide to come to the UW for graduate school?    

I came to the UW specifically for the Institute for Public Health Genetics (IPHG) program. Many universities have human genetics and medical genetics programs, but IPHG focuses on bringing a public health perspective to genetics research. IPHG students and faculty are not just interested in finding genetic causes of disease, they also study the accessibility of genetic testing, genetic privacy, who is included or excluded in genetics and genomics research, and how that impacts the interpretation of findings. I really wanted to study at an institution that prioritizes how research actually affects people.  

In your opinion, how do we improve health equity when it comes to public health genetics?  

Some people might think that genetics doesn’t belong in conversations about health equity because while genetic variation may cause health inequalities, these differences are “natural” or not rooted in injustice. However, genetics research that is not mindful of equity can actually be harmful and exacerbate injustices. One example of how genetics can play a role in improving health equity is in identifying who is more at risk for disease. This can help determine who should be prioritized for treatment.  

In clinical trials, this type of risk stratification can also be helpful to understand if treatments are more effective for individuals with a particular genetic variation. Precision medicine or precision public health is an ideal vision for these types of approaches; based on someone’s genetic background, we can ensure that the correct treatment is delivered at the right time. However, this leads to the possibility that genetics can be detrimental to health equity if not done carefully. A big problem in genetics and genomics is the imbalance of genetic information we currently have; we know a lot more about the genetics of disease for those who have European backgrounds compared to non-European or mixed backgrounds. To improve health equity, public health geneticists have a responsibility to understand the effects this disparity of data and knowledge has on results and to do a better job engaging underserved groups.  

Tell us about your research. What impact do you hope it will have?    

I study the genetics of Alzheimer’s disease (AD) and how the intersection of genetics and the environment impacts AD risk. Alzheimer’s is a hard and interesting disease to study because it is caused by a combination of genetic and environmental risk factors that differ across individuals. This complexity and heterogeneity make it difficult to predict and prevent. For the past decade or two, there have been major efforts to identify genetic variants associated with AD risk. My dissertation work involves using the results of those studies to compute scores that summarize individuals’ genetic risk for AD. I will then investigate the social and environmental factors that may confer protective effects against the disease for those who are at high genetic risk but have not been diagnosed with disease.  

Somewhat counterintuitively as a genetic epidemiologist, I hope the impact of my work demonstrates that genetics is not everything when it comes to Alzheimer’s disease and other complex diseases. Genetics can tell us a lot about the disease’s underlying biology and potential therapeutic targets, but environmental and social changes can also make a difference in disease prevention or delaying onset.  

You were recently awarded an F99/K00 grant from the National Institute on Aging. How does that award expand the research you have been doing on your dissertation and shape your research goals beyond your Ph.D.? 

I am grateful to have received the F99/K00 award because it not only supports the completion of my dissertation work, but also allows me to have continuity and some independence in my post-doctoral research goals. During my post-doctoral fellowship, I plan to dive deeper into the findings from my dissertation. While my dissertation work is focused on identifying more distal determinants — both genetic and contextual — as a post-doc, I will investigate the intermediate biological mechanisms that link those determinants to disease risk. For example, I hope to look at how social or environmental context modifies the associations between genetics and protein levels or protein folding changes. Investigating various biological layers will improve the understanding of how environmental differences manifest into differences in disease risk.  

What do you wish the general public knew about your area of research that might be misunderstood or not talked about enough?  

Alzheimer’s disease onset typically occurs in older people in their 60s, 70s and 80s, but pathological changes can start occurring 10 or even 20 years prior to clinical onset. New drugs have been recently approved to treat AD, but similar solutions for prevention don’t exist yet. This is where modifiable risk factors can come into play. There is evidence that education and physical activity can protect against AD or delay its onset, but these are also factors that people may not have that much control over. The modifiable risk factors I am interested in studying are not necessarily modifications at the individual-level. Changes in social funding or policy can influence an increase in the amount and quality of education, physical activity, etc., at the population level.  

What experiences at the UW SPH have been most influential?   

I have had incredible mentors at UW SPH, specifically Alie Fohner, IPHG associate director and assistant professor in the Department of Epidemiology, and Liz Blue, IPHG affiliated faculty and associate professor in the Division of Medical Genetics. I knew very little about public health genetics, AD genetics, and being in academia before working with them, and they have overseen my research and dissertation work since I started at the UW. They are exceptional researchers and people and I feel lucky to learn from them.  

What is one piece of advice that you have for new public health students or one thing you wish you knew before beginning your public health studies?   

I would encourage anyone who wants to go into public health to learn how to explain their research or work for different audiences because science communication is an important part of public health. Science communication does not have to be publishing a formal piece, but it will go a long way to be able to talk to your family friends about what you are learning. Once I started telling people that I study public health, I realized that everyone has questions about health, either for themselves or a loved one.    

What interests do you have outside of (or related to) public health? Any extracurricular activities?  

I organize the Public Health Genetics Journal Club and Progress in Research Seminar (PIRS). I really enjoy these opportunities to bring people from our program together because within our institute, people have such diverse research interests and perspectives. Outside of school and work-related activities, I run and play tennis. I also love to hang out with my friends and play board games, watch movies, or go on hikes.