Bone mineral density and osteoporosis: patterns, determinants and their relationships with cardiometabolic disorders in Chinese adults
Dr Wei Gan, Wellcome Trust Centre for Human Genetics
Osteoporosis is a common metabolic disease in which the bone mineral density (BMD) becomes decreased and can lead to an increased risk of fracture. It is becoming a major health concern worldwide because of its rising burden and the impact on quality of life and health care systems. Moreover, recent research in bone biology suggested that bone not only serves as a scaffold for other organs, but is also an endocrine organ involved in the regulation of glucose metabolism and testosterone production. However, the relationship between bone health and risk of cardiometabolic diseases has yet to be properly investigated.
The China Kadoorie Biobank (CKB) is a prospective cohort study of 0.5 million participants (www.ckbiobank.org), with extensive data (including measures of bone density in a subset) collected at baseline and periodic resurveys. After about 10 years of follow-up, >0.5 million ICD-10 coded episodes of hospitalisation of >1000 different disease types (e.g. stroke, heart disease, diabetes, osteoporosis, and fracture) were recorded among participants. Genome-wide SNP data are available for 100,000 participants (with the remaining 400,000 expected in the next few years). These are being complemented by assays of blood biomarkers (e.g. ~1000 metabolites, and ~200 inflammation and other biomarkers).
RESEARCH EXPERIENCE, RESEARCH METHODS AND TRAINING
This DPhil project aims to:
- Describe patterns of BMD-related measures provided by ultrasound, including T-score, broad band attenuation (BUA), sound of speed (SOS) and Stiffness index (SI) among ~25,000 adults in the 2nd CKB resurvey;
- Investigate the lifestyle determinants (e.g. physical activity, diet, smoking, alcohol use, tea consumption) of BMD-related measures and risk of osteoporosis;
- Assess the associations of biochemical factors (e.g. blood lipids, C-Reactive Protein, Creatinine, Vitamin D and Uric Acid) and other metabolic disorders (e.g. diabetes and cardiovascular disease) with BMD-related measures;
- Use genomic data to explore the genetic determinants of BMD and to conduct Mendelian randomisation analyses of bone density for their causal association with cardiometabolic diseases such as diabetes and cardiovascular disease.
The specific lines of investigation will be subject to further discussion and personal interest.
FIELD WORK, SECONDMENTS, INDUSTRY PLACEMENTS AND TRAINING
The project will provide an extensive range of training opportunities, including specific courses, seminars and conferences. There may be opportunities to become involved in fieldwork in China, depending on the direction and development of the project.
Students should have a 2.1 or higher degree in Medicine and an MSc in epidemiology, statistics, public health, or bioinformatics. Students should also have a strong interest in bone health research.