Approved Research

Genetic Analysis of Factors Influencing Chronic Liver Disease Risk in the UK Biobank

Lay summary

Chronic liver diseases are extremely common in the UK and other developed nations, affecting more than a third of the population.  Many patients with liver disease will experience few symptoms, in others however, their disease will progress to more severe forms that result in liver failure and require transplantation.  What causes some patients to progress to severe forms of liver disease while others do not, is not fully understood.  Certain chronic liver diseases have been shown to run in families, suggesting that there is a genetic cause in addition to environmental influences.  While certain genetic changes have been found to increase the risk of developing chronic liver disease, these known genetic factors cannot completely explain who is at risk of developing severe forms of chronic liver disease, therefore additional genetic variants may exist that influence the risk of disease progression.  To identify these genetic factors, we propose to examine existing DNA sequencing data that has been generated for patients enrolled in the UK Biobank.  Specifically, we will conduct a study over the course of 18 months that will use new statistical methods that our research group has developed to test the aim that patients with chronic liver disease carry rare genetic variation in certain genes that increases their risk of developing more severe forms of liver disease.  We also aim to test whether rare genetic variation is associated with the deposition of fat in the liver, or influences levels of certain proteins in the blood that are indicators of liver disease and metabolic dysfunction.  Discovery of these genetic factors could provide new targets for drug design and allow physicians to identify patients who are at risk of severe disease using a simple blood test instead of biopsy.