Approved Research

Decoding the pathogenesis of digestive disorders and developing predictive tools using phenotypic and genomic data from the UK Biobank

Lay summary

Many digestive disorders, such as inflammatory bowel disease and non-alcoholic fatty liver disease, are complex disorders with remarkable heterogeneity. Emerging evidence indicated that environmental and genetic factors are major contributors and exert their effects synergistically on the disease onset and progression. Currently, the underlying mechanisms remain elusive, and consequently, such diseases still place a huge economic burden on modern society. However, with the advent of the population-level large-scale prospective cohorts and the development of high-throughput technologies, we are now equipped with multiple powerful tools and are able to disentangle this by integrative analysis of both phenotypic and genomic/transcriptomic data. In this project, our interdisciplinary team will use clinical epidemiology approaches as well as molecular epidemiology methods to examine the following key questions in the GI field: (1) to identify the modifiable risk factors and biomarkers to elucidate their (moderating) functions on disease development; (2) to develop a set of predictive tools for the prediction of disease onset, disease progression, and etc., for the early detection of high-risk population; (3) to discover new genetic variants and candidate genes associated with digestive disorders and phenotypic traits; (4) to uncover the genetic correlations among digestive disorders and other complex diseases and their comorbidities; (5) to infer potential causal associations between modifiable risk factors and the digestive disorders; (6) to provide mechanistic insight into how the candidate genes in specific cell types exert their effects on disease development; (7) to identify potential molecular targets for drug discovery and drug repurposing. Our combinatorial and systematic approaches will allow us to develop user-friendly prognostic algorithms and interfaces, generate summary-level data for the GI community, and have a better understanding of disease pathogenesis and drug treatment for the benefits of both primary prevention in general practice and secondary/tertiary prevention for hospitalized patients. The findings from this study will aid health-care providers to identify high-risk individuals for certain digestive disorders, and ultimately develop personalized treatment accounting for genetic backgrounds. This research project is computational-demanding, we anticipate 36 months but depending on the outcomes, we may request an extension.