Approved Research

Identification of biomarkers of chronic diseases using epidemiological and genomic information from the UK Biobank

Lay summary

This study aims to look at the interconnection between metabolic syndrome, diabetes, and nonalcoholic fatty liver disease (henceforth, NAFLD). Globally, the mortality rate from chronic diseases increases significantly as the aging population grows. An individual's chronic disease risk is related to genetic factors, environment, and the interaction between these two genetic and environmental factors. Among chronic diseases, metabolic syndrome, diabetes, and NAFLD are very closely connected. NAFLD is associated with obesity, insulin resistance, diabetes, and hypertriglyceridemia. Furthermore, NAFLD is widely considered the hepatic manifestation of metabolic syndrome. Roughly 90% of the patients with NAFLD have more than one feature of metabolic syndrome, and about 33% have three or more criteria. And the addition of each of the components of metabolic syndrome synergically drives the risk of fatty change in the liver (called steatosis). NAFLD has been showing consistent associations with obesity (60-95%), type 2 diabetes (28-55%). Moreover, between 5% and 12% of people with steatosis will progress to severe scarring of the liver (called cirrhosis), then the incidence of liver cancer in cirrhotic is about 30%. These days, NAFLD-associated liver cancer prevalence is estimated to increase (47% increase in Japan; and 130% increase in the US). At the same time, cancers aid tumour microenvironment and cellular composition to impose metabolic proteins and pathways for tumour progression and metastasis. Currently, there are no reliable biomarkers (including clinical parameters or genetic markers) to monitor progressions of NAFLD, metabolic syndrome, and diabetes. In this study, we aim to confirm the interconnection between metabolic syndrome, diabetes, and NAFLD and to identify genetic biomarker candidates of the progression of these chronic diseases. Therefore, discovering biomarker candidates involved in the progression of metabolic syndrome, diabetes, and NAFLD may improve the patient's outcome and quality of life. By identifying these biomarker candidates then it is possible that treatment is available to start to prevent complications before they progress. We aim to complete this project over 36 months with a publication of our findings at the end of that timeframe.