The Mexico City Prospective Study

Experience in Western countries has shown that large population-based prospective studies are a valuable way of investigating many slow-acting causes of common chronic diseases. Over 15 years ago, we enrolled 150,000 Mexicans (100,000 women and 50,000 men) into the Mexico City Prospective Study (MCPS), asking them about their lifestyle, taking their physical measurements and storing their blood samples (allowing genetic variation to be measured). We have established reliable follow-up of cause-specific mortality and have recently reassessed a sample of 10k participants (predominantly to find out how risk factors change vary over time). We are also about to start a new programme of fieldwork to collect information on major non-fatal diseases that have occurred over the past 15 years. The MCPS is the largest prospective study that has been established among Mexicans (or Mexican Americans) and with >15 years of follow-up is now very well placed to examine the major genetic and non-genetic causes of disease in this population. In particular, a major problem in Mexico is obesity and diabetes (and, as a consequence, kidney disease and cardiovascular disease). Much of our future research will therefore be to investigate how obesity, diabetes and related risk factors (including genetic factors) inter-relate to cause premature morbidity and mortality in Mexican adults.

Between 1998 and 2004, the Mexican Ministry of Health, in collaboration with epidemiologists at the University of Oxford’s Clinical Trial Service Unit & Epidemiological Studies Unit (in which the PHRU is embedded), established in Mexico City a prospective study in which over 150k middle-aged adults were enrolled (the ‘Mexico City Prospective Study’ [MCPS]). Participants completed a questionnaire, had a physical assessment (weight, height, waist and hip circumference, blood pressure) and gave a blood sample. Stored plasma and buffy coat samples (for DNA) of good quality are available for 98% of participants and are in long-term storage in Oxford in liquid nitrogen storage facilities. Participants are tracked for cause-specific mortality using the national mortality register, with nearly 20k dead by 2016. A resurvey of 10k survivors, including additional questions, measurements, and samples (urine) was completed in February 2019. Cohort-wide fieldwork to collect information on major non-fatal diseases will start in mid-2019. Funding to genotype and exome sequence the whole cohort has recently been obtained.
The MCPS is by far the largest study of its type in a Latin-American population. What sets it apart from other large blood-based cohorts is the extremely high prevalence of obesity and diabetes. By age 60, around half of women and one third of men had a body-mass index of at least 30 kg/m2 at recruitment, while more than one in five had received a diagnosis of diabetes. Those with diabetes had poor glycaemic control (mean HbA1c was 9%) and had an all-cause mortality rate at ages 35-74 that was four times greater than those without diabetes (much more extreme than has been documented in other populations studied to date).
We plan to continue to follow-up as well as enhance the cohort (eg, with the collection of information on non-fatal diseases) with the primary aim of continuing to study the major known environmental causal risk factors. However, the availability of genetic data in addition to a wide range of other phenotypic data that already exists – from a single study with >15 years follow-up covering a wide range of diseases, and in an admixed population in which adiposity and diabetes are much more common than in most previously-studied populations – creates substantial new research opportunities. These include: discovery of novel genetic variants for diabetes, adiposity and related traits; replication and fine-mapping studies, and trans-ethnic meta-analyses; causal evaluation of environmental risk factors and blood biomarkers (through Mendelian randomisation studies); phenome-wide association studies; creation of risk prediction tools; and genome wide association studies of other traits. The potential subsequent translational opportunities (eg, with respect to the development of novel therapeutic approaches) are substantial.