Diet, biomarkers and non-communicable diseases in rural and urban China: federated analysis of population-based studies

Diet (i.e. intake of specific foods, nutrients, and overall dietary patterns) plays an important role in the development and progression of NCDs, which is the leading cause of early death and disability. However, the majority of the previous studies were conducted in high-income Western countries, with limited information available from low- and middle-income countries (LMICs), such as China, where nearly three-quarters of NCDs occur. This lack of robust information makes it difficult to formulate evidence-based dietary guidelines for NCD prevention in these countries. More importantly, associations observed only in a specific population (or few similar populations) may not be the true effect of diet, but due to the impact of other factors which are closely related to dietary habits, e.g. socio-demographic factors or other lifestyle factors (e.g. physical activity). Therefore, studying the association between diet and NCDs in LMICs has become very important because populations in these countries, compared to those living in Western countries, have very distinct dietary and disease patterns and the correlations between dietary factors and socio-demographic factors are also very different. Moreover, the exact biological mechanisms through which diet exert its effect on NCD incidence and progression is largely unknown. A better understanding of such mechanisms will greatly enhance our capacity to effectively prevent and treat these diseases. In this proposal, we plan to bring together several large population based studies which in total involves > 1 million Chinese adults for whom information on dietary habits, biomarkers which are closely related to metabolism status of the body, and incidence of NCDs is available, together with long-term stored bio-samples. Joint analyses of existing as well as newly generated omics (i.e. MS-Metabolomics and Metagenomics) data will be performed in order to have a comprehensive robust assessment of diet and NCD association as well as potential underlying mechanisms.

It has been well established that diet (i.e. specific foods, nutrients, and overall dietary patterns) plays an important role in the development and progression of NCDs. However, the majority of the available evidence comes from observational studies conducted in high-income Western countries and the understanding of the mechanisms by which different dietary factors affect risk of NCDs remains incomplete. Therefore, investigating the associations of diet with NCDs and elucidating the mechanisms underlying such associations in populations from LMICs is very important. In this proposal, we plan to perform federated analysis of individual-level data from multiple nutrition studies conducted in China, in total involving >1.0 million adult Chinese in rural and urban areas. This approach offers the possibility to use data in new efficient ways, thereby increasing the diversity of samples and sample related data, enlarging the sample size, enhancing the robustness of statistical subgroup analysis, improving the generalizability of results, and helping ensure the validity of comparative research findings. More importantly, joint data analysis will encourage collaborative initiatives to plan future specific high-throughput sample assays (i.e. MS-metabolomics and metagenomics) in order to answer complex questions in studying the role of diet in metabolism regulation. We will devise centralised statistical analysis plans that utilise state-of-the-art statistical methods to comprehensively assess the associations of various dietary factors with NCD incidence and mortality, traditional markers (e.g. BMI, BP, LDL-cholesterol, liver steatosis, and CRP), subclinical measures of NCDs (e.g. carotid plaque, liver steatosis, and bone mineral density), and novel omic markers (e.g. genomics, metabolomics, protomics, metagenomics, and epigenomics).

We will establish a new collaboration between CKB research team and China CDC in order to perform a federated analysis to reliably assess the mechanistic links between various dietary variables and NCDs in China. It is envisaged that the proposed project will achieve significant scientific impact via the dissemination of findings through high impact peer-reviewed publications in scientific journals, national and international conferences, seminars, and workshops. The findings generated will contribute to evidence-based NCD prevention strategies, bridge the current knowledge gap on mechanistic links between diet and NCDs, produce novel hypotheses, and enhance the understanding of NCD aetiology.
In addition, this proposal will expand the educational impact of the CKB, which has an excellent track record of training next-generation researchers in both China and the UK. For the last few years, Chinese health researchers have been seconded to Oxford for up to a year to receive training in epidemiological research methods and statistical analysis techniques. The proposed collaboration will facilitate the sharing of knowledge and experience, and contribute to the scientific development of junior researchers. Our ultimate goal is to provide junior and emerging academics with first class training in study design, data management, data analysis, result interpretation, and dissemination of results in a collaborative research environment. In addition, CKB is an open-access resource and new data generated through this proposal will be made available to scientific community in due course.
Our research will have profound societal impact as well. Through public engagement events, social media outlets, and relevant web-sites, our findings will inform public health debate on the importance of diet in NCD prevention. We will also engage key stakeholders, including local and national government officials, academic and research institutions, food industries, health professionals, community leaders, and general public for effective delivery and communication of our research findings. The University of Oxford has established communication teams who will assist in designing clear and effective communication materials that can reach a wide variety of individuals, research organisations, funders and health professionals.