Stefan Stender

Project title

Using genetics to predict development and progression of fatty liver disease

What is your project about?

With a prevalence of 20% to 45%, fatty liver disease has reached epidemic proportions. However, only a subset of those with hepatic steatosis, the first stage of the disorder, go on to develop severe liver diseases such as cirrhosis and hepatocellular carcinoma. We currently lack effective methods to identify these 'progressors’ early, before they reach an irreversible disease stage. We hypothesize that genetic factors play a key role in fatty liver disease progression. The aims of this study are to: 1) identify and characterize new genetic risk factors for fatty liver disease, 2) combine the individual genetic factors into a risk score, and 3) test if a higher genetic risk score predicts disease progression. We will utilize four cohorts from the UK, US, and Denmark totalling >600,000, including >1,000 patients with various stages of fatty liver disease. The study may open new avenues to the prediction and prevention of fatty liver disease progression.

How did you become interested in your particular field of research?

My interest in genetics was sparked during my PhD at the Department of Clinical Biochemistry at Rigshospitalet. We examined the heritable risk of gallstones and ischemic heart disease in the Copenhagen City Heart Study and the Copenhagen General Population Study, large cohorts of the Danish general population. These studies made it obvious to me that genetic epidemiology is a powerful tool to shed light on causal mechanisms underlying human disease. My interest in genetics was deepened during my time as a post-doctoral fellow at the University of Texas Southwestern Medical Center in Dallas. We studied the genetics of fatty liver disease using population-based cohorts and experimental studies in cells and animals. 

What are the scientific challenges and perspectives in your project?

This project combines genetics and large-scale epidemiology to reveal causal pathways in fatty liver disease. Identification of the principle genetic factors that influence fatty liver disease will facilitate the definition of the complete pathophysiology of the disease. A major challenge of the project is that fatty liver disease is hard to measure precisely. In this project, we rely to a large extent on indirect markers of the disease. To ensure that the newly discovered genetic associations truly relate to fatty liver disease, we will validate them in independent cohorts of patients with fatty liver disease measured by state-of-the art imaging methods. Only those genetic risk factors that can be robustly validated will be considered true.

What is your estimate of the impact, which your project may have to society in the long term?

The identification of new genetic risk factors for fatty liver disease might open avenues to control the influence of specific environmental risk factors, and could inspire the design of new interventions and drugs. If we succeed in showing that a genetic risk score predicts disease progression, a similar risk score could potentially be used by clinicians to predict and prevent disease progression in patients with fatty liver disease.

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

This Sapere Aude grant makes it possible for me to begin to build a research group. In addition, it strengthens my bonds to my international collaborators in Bristol and San Diego, and to my Danish collaborators. Finally, the Sapere Aude programme is a strong brand, and is recognized across scientific fields in Denmark and abroad. I therefore anticipate that this grant will help open doors to new collaborations in the future.