Genetic Susceptibility to Infection in Wisconsin Hmong

This is a great example of the Wisconsin Idea. … This is something we should be doing — the state and the university working together for the benefit of public health and people in Wisconsin.

– Dr. Bruce Klein from a UW–Madison press release by Kelly April Tyrrel

At a Glance

In Wisconsin, people of Hmong ancestry are infected by a particular fungal lung disease at rates up to 100 times higher than people of European ancestry, a concerning public health disparity.

The researchers identified the genetic basis for susceptibility to the fungal infection in people of Hmong ancestry, providing new opportunities for treatment and education.

The Challenge

Fungal infections can be very serious, and often disproportionately affect particular ethnic groups. In 2009-2010, 55 people were infected by an outbreak of blastomycosis in Marathon County, Wisconsin, twenty of whom were Hmong, and Hmong Wisconsinites were again disproportionately impacted by an outbreak in 2015.
Scientists have long suspected that higher susceptibility in different populations is genetically-based, but had yet to understand the patterns and identify the individual genes and mutations involved. This project used advanced sequencing techniques to study samples of DNA from Hmong individuals who had been exposed to blastomycosis and analyze them to determine what differences caused the lower immunity.

Project Goals

The overarching goal of the research was to identify the genetic basis for the higher susceptibility to fungal infection in Wisconsin’s Hmong population. To accomplish this, the researchers identified two particular goals for their genetic analyses:

• Identify genetic loci linked with susceptibility to blastomycosis in the Hmong population
• Define the role of single nucleotide polymorphisms, SNPs, in regulating gene transcription and immunity to infection

Results

The study achieved its major goal, and identified the genes involved in impaired immune response to blastomycosis. The key finding of this study is that Hmong individuals are much more likely to have two identical copies (one from each parent) of genes that are important in producing two immune responders that promote resistance to many fungal infections, interleukin-6 and interleukin-17. Having two different copies is associated with a higher likelihood of stronger immune response to blastomycosis. However, fewer Hmong individuals that European individuals have different copies because Hmong populations historically have been more isolated and less genetically diverse. This lack of different copies of the gene causes Hmong individuals to be more susceptible to infection.

The findings have been published in the Hmong Studies Journal and mBio, where they were highlighted by the journal. A university press release and several articles covered the study. A third publication is pending.

Lasting Impact

The study sheds light on the genetic underpinnings of a significant health disparity in Wisconsin. The results provide new opportunities for precision medicine, public health education in Hmong, and insight into vulnerabilities to infections in other patients that may be treated with medication that undermines the function of interleukin-6, an important immune responder. The study also contributes to a growing body of knowledge on the genetic basis of susceptibility to infectious fungal diseases, which has broader implications for community health and personalized medicine that can be applied beyond the context of Hmong communities in Wisconsin.

In 2017, the project leveraged a F30 training grant from the National Institute on Minority Health and Health Disparities for $157,962 over four years to support a MD-PhD student to continue these important studies of the pathogenesis of fungal infectious disease in the Hmong population.