Program explores molecular underpinnings of chronic diseases

December 4, 2019—For many years, epidemiological data has shown a link between obesity and asthma. While researchers have long hypothesized that obesity increases the risk of asthma, why or how that risk is increased isn’t entirely clear.

A recent study led by Harvard T.H. Chan School of Public Health, however, found for the first time common genetic factors and a polygenic background shared between obesity and certain types of asthma.

“These findings give us a much better understanding of the role genetics play between obesity-related traits and asthma subtypes,” said Zhaozhong Zhu, lead and co-corresponding author of the study. Yanjun Guo was also a co-first author of the study. Both Zhu and Guo are postdoctoral fellows in the Program in Genetic Epidemiology and Statistical Genetics (PGSG).

The study is one of several recent research publications to come from the laboratory of Liming Liang, associate professor of statistical genetics, that illuminate the intersection of genetic factors and health risks. In his role at PGSG, Liang has worked closely with members of his lab to develop new methods to better understand the genetic underpinnings of some of the world’s biggest public health challenges.

Obesity and asthma 

Obesity and asthma are growing problems worldwide. More than 300 million people are living with asthma, while obesity rates are climbing higher.

To examine possible genetic factors implicated in both diseases, the study, published in the Journal of Allergy and Clinical Immunology, analysed data collected from more than 460,000 people through the UK Biobank—a giant repository that stores biological samples from participants and is linked to their electronic medical records. Using a new analytical pipeline implemented by Zhu, the team was able to identify genetic commonalities between obesity and asthma.

The findings have both immediate and long-term implications for public health, Zhu said. “Our short-term goal is to get the message out to people that obesity could lead to asthma in adults through shared genetics. As such, we should be encouraging people to make environmental changes, such as modifying one’s diet to consume fewer low-quality carbohydrates, which could possibly help prevent asthma.”

Guo added that the current findings could provide important information to aid in the development of precision medicines to manage and treat obesity and asthma.

Interdisciplinary approach 

The possible impact of research like Zhu’s has long excited Liang. He first joined PGSG in 2009, drawn by the program’s interdisciplinary approach to deciphering the molecular mechanisms that underlie a host of chronic diseases and cancers.

“PGSG is specialized in developing novel statistical approaches and computation tools to tackle important public health problems by using real-world multi-omics studies,” Liang said. “Postdocs and students in the program have unmatched opportunities to work on high-quality large-scale datasets with leading experts from various fields.”

Members of PGSG regularly collaborate with researchers at Harvard Chan School, Harvard Medical School and affiliated hospitals, The Broad Institute, and other international institutes. The focus is often on devising new methods in statistical genetics to make better use of giant data sets and redefine our understanding of how human genes and the environment shape population-level health trends.

Postdocs working with Liang have covered a broad spectrum of health issues. For instance, a recent study in the Journal of the American College of Cardiology looked at how genetics may influence the link between type 2 diabetes and high resting heart rate (RHR).

“Our data showed significant genetic correlation between RHR and type 2 diabetes, and even indicated potential causality between them,” said  Guo, first author of the study. “This is important information for public health practitioners because it may indicate that healthy lifestyles and healthy eating choices that lower RHR may also lower the risk of cardiometabolic disorders.”

Another paper led by Zhu and Liang found shared genetic architecture between asthma and eight mental health disorders, including attention deficit hyperactivity disorder, anxiety disorder, and major depressive disorder. Based on data from more than 700,000 individuals from the UK Biobank and the Psychiatric Genomics Consortium, the findings, published in the European Respiratory Journal, provide important insights into a phenomenon that has intrigued scientists for more than a century.

“Back in the 20th century, scientists had found the association between asthma and mental health disorders, in both children and adults,” Zhu said. “However, the mechanisms contributing to such association have largely remained unknown until now.”

Whether about type 2 diabetes, asthma, or obesity, the projects that Liang and his postdocs take on help fill gaps in knowledge and provide tools for other researches to experiment with in their respective fields. Liang is eager to see the findings from his team translated into impactful public health interventions, such as new personalized medicines or lifestyle guidelines for certain high-risk populations.

“The work of our team and everyone at PGSG is just starting to help us understand the unique and shared genetic architectures of complex human disease and traits,” Liang said. “There is so much we still need to learn in terms of their biological mechanism, causal relationship, risk predictability, and implication in clinical and public health practices. But we’re making progress every day.”

photo: Pixabay

Chris Sweeney