Infrastructure support for the Mexico City Prospective Study

Large population-based prospective cohort studies are a useful way to determine the impact of many slow-acting causes of disease and have previously been used to identify the major 'classic causes' of premature death from non-communicable diseases, including smoking, hypertension, obesity (adiposity), harmful alcohol use, dyslipidaemia, diabetes, poor diet and physical inactivity. The relatively-recent availability of high-throughput low-cost genotyping has led to further advances in epidemiology, both in the discovery of new genetic causes of diseases (with subsequent development of drugs targeting new pathways) and the causal evaluation of disease risk factors (through 'Mendelian Randomisation' studies). However, existing large prospective cohort studies have disproportionately studied high-income populations of European ancestry. Large blood-based prospective studies in a range of populations that differ with respect to their health care settings and exposures to environmental and genetic risk factors are needed to fully understand the causes of human disease worldwide.

The Mexico City Prospective Study (MCPS) represents a long-standing collaboration between scientists at the National Autonomous University of Mexico in Mexico City and the University of Oxford. Between 1998 and 2004, over 100,000 women and 50,000 men aged =35 years from two districts of Mexico City were recruited, provided information on socio-demographic and lifestyle characteristics, disease history and medication, had physical measurements taken, and gave a blood sample (with plasma and buffy coat stored in Oxford ever since). A resurvey of 10,000 survivors carried between 2015 and 2019 included phenotypic enhancements and assessed the repeatability of risk factors over time. All participants have been genotyped and exome sequenced, and had baseline and resurvey HbA1c and lipidomics (using Nightingale Health's NMR platform) measured. Participants have been tracked for cause-specific mortality for >20 years; by mid-2022, about 35,000 participants had died and by 2029 about 50,000 will have. Information on major non-fatal diseases is also now being collected through house-to-house fieldwork (with information currently available for about one quarter of the original cohort). MCPS data are available for open access data requests with no data access fees for researchers in low or middle-income countries, and preferential access and free compute time for genetic analyses given to researchers in Mexico.

To maximise the potential for scientific discoveries to be made on the causes of disease in this Latin-American population, the aims during the next 5 years are: 1) continue to enhance the data available through the collection of information on non-fatal as well as fatal diseases; 2) perform new biological assays on the stored baseline blood samples; 3) support and expand local infrastructure in Mexico; 4) increase collaboration with local and international research consortia to maximise the scientific outreach of the study; and 5) curate and then make available all of the data for academic researchers worldwide. With long-term follow-up and a large sample size (and hence many disease cases to study), MCPS is extremely well-placed to investigate the interplay between lifestyle, environmental and genetic causes of disease in this Latin-American population. The scientific discoveries made on them by increasing numbers of researchers worldwide promise benefits not only for Hispanic but for all populations. MCPS has been supported by the MRC through Unit funding for over a decade. The current application is for continuation of the infrastructural component of the study through the longitudinal prospective study scheme to replace Unit funding (which will cease in March 2024).