Identification of genetic and environmental factors involved in the aetiology of rheumatic and musculoskeletal diseases

In this project, we will conduct a series of studies focusing on identifying the genetic and environmental factors involved in the aetiology of rheumatic and musculoskeletal diseases (RMDs) using the UK Biobank database. RMDs are ageing-related diseases characterized by degeneration of muscles, bones, joints, tendons and ligaments. The socioeconomic burden of RMDs has increased significantly with the trends of ageing in global population. Moreover, they have become the second leading cause of years lived with disability worldwide. However, the exact causes of RMDs are not well understood, leading to inefficient or undesirable prevention and treatment approaches for controlling these diseases. RMDs are likely to be caused by both genetic and environmental factors, but there is a paucity evidence of specific genetic and environmental factors for this disease. First, the heritabilities of RMDs are pretty high. Although several common loci have been identified as genetic factors for RMDs, these established common variants only account for a small proportion of the disease heritability. Second, RMDs are often multifactorial and influenced by both genetic variants and environmental factors (such as smoking, diet patterns, obesity, levels of physical activities, and previous injury), and the results of traditional environmental factors for RMDs from previous observational studies are susceptible to residual confounding and selection bias. Third, the potential time sequency of RMDs and other common health conditions (i.e., cardiovascular diseases, chronic kidney diseases and coronavirus disease 2019) has not been fully elucidated, and data from the UK Biobank provides a unique opportunity to clarify causal relationship between RMDs to other conditions. The results will help us better understand the biological mechanisms and genetic pathogenesis underlying RMDs. Accordingly, they would provide potential targets for drug development and effective prevention. We anticipate the project duration to be three years.