The Mexico City Prospective Study

Lead Research Organisation: University of Oxford

Abstract

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.

Technical Summary

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.

Publications

10 25 50
 
Description Seed Funding
Amount $25,000 (USD)
Organisation World Heart Federation 
Sector Charity/Non Profit
Country Switzerland
Start  
 
Description Abbvie 
Organisation AbbVie Inc
Department AbbVie (UK)
Country United Kingdom 
Sector Private 
PI Contribution Collaborative research projects using genetic data from the MCPS
Collaborator Contribution Abbvie contributed to the whole genome sequencing of 10,000 selected individuals from MCPS.
Impact None yet (imputation serveral expected to be launched later in 2022)
Start Year 2021
 
Description Astra Zeneca 
Organisation AstraZeneca
Department Astra Zeneca
Country United States 
Sector Private 
PI Contribution Collaborative research projects using genetic data from the MCPS.
Collaborator Contribution In addition to the funding provided by joining the already-existing partnership between Oxford, Mexico and Regeneron, Astra Zeneca also contribute through regular scientific meetings with the teams in Mexico, Oxford and Regeneron.
Impact None yet (but several expected outputs in 2022).
Start Year 2021
 
Description General Hospital of Mexico 
Organisation General Hospital of Mexico
Country Mexico 
Sector Hospitals 
PI Contribution Collaboration with Prof Jaime Berumen, Head of the Genomic Medicine Unit at the General Hospital of Mexico (Faculty of Medicine, National Autonomous University of Mexico). Aim: To study the genetic causes of disease in the Mexican population (PI: Emberson; Co-investigators: Torres) Formal agreement in development
Collaborator Contribution academic partnership
Impact Discovery of GPR75 as a novel target for protection from obesity (Akbari et al. Science 2021).
Start Year 2020
 
Description MRC Cross-Population Mendelian Randomization Network 
Organisation University of Bristol
Department MRC Integrative Epidemiology Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution To address the challenges in generalisability of target drugs for multiple populations and evaluate how Mendelian randomization can be used to address them.
Collaborator Contribution Cross-collaboration with researchers at the MRC Integrative
Impact none yet
Start Year 2022
 
Description Nightingale Health 
Organisation Nightingale Health Ltd.
Country Finland 
Sector Private 
PI Contribution To study the relevance of NMR biomarkers for the prediction of diabetes in UK and Mexican adults using data from the UK Biobank and the Mexico City Prospective Study (PI: Emberson; Co-investigators: Aguilar-Ramirez, Trichia, Bragg).
Collaborator Contribution Academic collaboration
Impact Manuscript under review. Pre-print available on MedRriv: https://www.medrxiv.org/content/medrxiv/early/2021/10/14/2021.10.11.21264833.full.pdf
Start Year 2020
 
Description Regeneron Genetics Center 
Organisation Regeneron Pharmaceuticals, Inc.
Country United States 
Sector Private 
PI Contribution Collaborative research projects using genetic data from the MCPS.
Collaborator Contribution The Regeneron Genetics Center genotyped and exome sequenced the entire MCPS cohort (an 'in-kind' contribution valued at the time as being >$100M) and continues to contribute through regular joint scientific meetings.
Impact Discovery of GPR75 as a novel target for protection from obesity (Akbari et al. Science 2021).
Start Year 2019
 
Description The Metabolic Analysis in an Indigenous Sample (MAIS) cohort 
Organisation Government of Mexico
Department National Institute of Genomic Medicine, Mexico
Country Mexico 
Sector Public 
PI Contribution Collaborative research to better understand the local ancestry of the individuals in the MCPS cohort.
Collaborator Contribution The MAIS Investigators provided individual level genetic data to Oxford for 716 individuals from 60 of the 68 recognized ethnic groups in Mexico. Oxford. The Oxford and MAIS investigators are currently working together (with Mexico, Regeneron and Astra Zeneca) on joint analyses.
Impact none yet
Start Year 2021
 
Description Online research symposia for the Centre for Personalised Medicine 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Jason Torres. Co-organiser of two online research symposia for the Centre for Personalised Medicine, both of which are available to the general public (one on metabolic health [https://cpm.well.ox.ac.uk/term/pm-practice-genes-behaviour-and-metabolic-health] and the other on health disparities [https://cpm.well.ox.ac.uk/term/facing-disparities-healthcare]).
Year(s) Of Engagement Activity 2021
URL https://cpm.well.ox.ac.uk/term/pm-practice-genes-behaviour-and-metabolic-health
 
Description School visit Causeway School, Eastbourne 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact • Speaker at post-16 provision fair, Causeway School, Eastbourne
Year(s) Of Engagement Activity 2019