USC launches liver disease study as part of $50.3 million “multi-omics” consortium

The Keck School of Medicine of USC has received funding from the National Institutes of Health as part of a five-year, $50.3 million “multi-omics” study of human health and disease involving six sites. Researchers in the Multi-Omics for Health and Disease consortium will study fatty liver disease, hepatocellular carcinoma, asthma, chronic kidney disease, preeclampsia and other conditions, with a focus on underrepresented racial and ethnic groups.

Throughout the study, researchers will use cutting-edge methods to collect a variety of biological data—including genomics, epigenomics, and transcriptomics—as well as information on patients’ social and environmental circumstances. By combining these datasets over the study period, the consortium aims to answer key questions about the cause of various diseases, as well as develop new tools for diagnosis and treatment. The Keck School of Medicine group will focus primarily on Hispanic patients, ages nine to 18, with non-alcoholic fatty liver disease (NAFLD).

“This is a silent epidemic,” said Vaia Lida Chatzi, MD, PhD, a professor of population and public health sciences at the Keck School of Medicine and one of the consortium’s principal investigators. “NAFLD usually causes no symptoms. Once children go to the doctor, they may already have damage to the liver.”

For that reason, it’s critical to learn more about the condition’s basis, as well as ways to prevent it, said Max Aung, PhD, an assistant professor of population and public health sciences at the Keck School of Medicine and a principal investigator for the consortium. Already the most common liver disease, NAFLD is on the rise among both Hispanic Americans and in children.

“We’re conducting the first and largest longitudinal study of pediatric NAFLD and at the same time, we’re studying a population that has been historically neglected in biomedical research,” Aung said.

The power of multi-omics

To date, most longitudinal studies of human disease have tracked a single type of “omics” data, such as genomics (DNA), transcriptomics (RNA), epigenomics (chemical modifications that affect DNA function), proteomics (proteins that can affect cell function) or metabolomics (other molecules involved in cellular metabolism). But that approach can miss key relationships between various “omics” data, such as how changes in DNA relate to levels of various cellular proteins.

“By having all of this information available in the same dataset, we can learn more about biological mechanisms, and improve our ability to find biomarkers to use in the clinic,” Aung said.

NAFLD is typically diagnosed through a combination of enzyme testing and imaging, which can be expensive and may delay detection of the condition in some populations. Finding a reliable marker of the disease that can be detected in blood samples could help patients get treatment sooner, Chatzi said.

“If we have biomarkers that can be validated, that will be really useful for clinicians, both for early diagnosis and for evaluating the severity of the disease as it progresses,” she said.

Social and environmental factors 

In addition to studying the biological basis of various diseases, researchers in the consortium will collect data on social and environmental factors that may help explain why some populations face a heightened risk. For example, the Keck School of Medicine team is collaborating with Sonoma Technology to estimate air pollution exposure across time and space for each patient they recruit.

Aung and Chatzi are also collaborating with the Southern California Center for Latino Health on a community engagement strategy that will involve recruitment of a community advisory board and development of a communication strategy for disseminating research findings to participants, as well as their families and communities.

The research team will begin recruitment in the fall at Children’s Hospital Los Angeles (CHLA) in collaboration with Tania Mitsinikos, MD, Alaina Vidmar, MD, and Rohit Kohli, MBBS, following a consortium-wide meeting to develop the scientific agenda for the next five years. The CHLA team has a long history of successful clinical studies in youth with obesity and fatty liver disease. In addition to specific disease insights, the team aims to develop research methods and analytic techniques that can be used in future longitudinal studies of multi-omics data. Tanya Alderete, PhD, from University of Colorado Boulder, is also collaborating on the study.

“Multi-omics is the frontier of biomedical and environmental health research, and our team at USC is committed to advancing the best available science and methods to pursue this,” Aung said.

About this research

In addition to USC, the consortium’s other study sites are the University of California, San Diego; the University of California, San Francisco; Columbia University; the University of Illinois Chicago; and the University of Texas Health Science Center.

This work is jointly supported by National Human Genome Research Institute, the National Cancer Institute and the National Institute of Environmental Health Sciences.