The Mexico City Prospective Study
Lead Research Organisation:
University of Oxford
Department Name: UNLISTED
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.
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.
Organisations
- University of Oxford (Lead Research Organisation)
- AbbVie Inc (Collaboration)
- AstraZeneca (Collaboration)
- UNIVERSITY OF OXFORD (Collaboration)
- Mexican Biobank (Collaboration)
- Nightingale Health Ltd. (Collaboration)
- International Common Disease Alliance (Collaboration)
- Regeneron Pharmaceuticals, Inc. (Collaboration)
- Hospital General de México (Collaboration)
- Government of Mexico (Collaboration)
- University of Bristol (Collaboration)
Publications
Alegre-Díaz J
(2022)
Body mass index and COVID-19 mortality: prospective study of 120 000 Mexican adults.
in International journal of epidemiology
Gnatiuc L
(2022)
Abdominal and gluteo-femoral markers of adiposity and risk of vascular-metabolic mortality in a prospective study of 150 000 Mexican adults.
in European journal of preventive cardiology
Akbari P
(2022)
Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes.
in Nature communications
Ziyatdinov A
(2023)
Genotyping, sequencing and analysis of 140,000 adults from Mexico City.
in Nature
Carter JL
(2023)
Body composition and risk factors for cardiovascular disease in global multi-ethnic populations.
in International journal of obesity (2005)
Jin D
(2023)
Lipoprotein Characteristics and Incident Coronary Heart Disease: Prospective Cohort of Nearly 90 000 Individuals in UK Biobank.
in Journal of the American Heart Association
Trichia E
(2023)
Alcohol and cause-specific mortality among 150,000 participants in the Mexico City Prospective Study
in European Heart Journal
Turner M
(2023)
Mendelian randomization study of the relevance of blood pressure to vascular mortality among 150,000 participants in the mexico city prospective study
in European Heart Journal
Staplin N
(2023)
Relationship between clinic and ambulatory blood pressure and mortality: an observational cohort study in 59 124 patients.
in Lancet (London, England)
Rajagopal V
(2023)
Rare coding variants in CHRNB2 reduce the likelihood of smoking
in Nature Genetics
Addey T
(2023)
Educational and social inequalities and cause-specific mortality in Mexico City: a prospective study.
in The Lancet. Public health
Gnatiuc Friedrichs L
(2023)
Body Composition and Risk of Vascular-Metabolic Mortality Risk in 113 000 Mexican Men and Women Without Prior Chronic Disease.
in Journal of the American Heart Association
Gnatiuc Friedrichs L
(2023)
Physical activity and cause-specific mortality among 150,000 participants in the Mexico city prospective study
in European Heart Journal
Bragg F
(2023)
Diabetes and infectious disease mortality in Mexico City.
in BMJ open diabetes research & care
Bragg F
(2024)
Social and spatial inequalities in premature mortality across Europe.
in The Lancet. Public health
Related Projects
Project Reference | Relationship | Related To | Start | End | Award Value |
---|---|---|---|---|---|
MC_UU_00017/1 | 31/03/2019 | 31/03/2024 | £5,782,000 | ||
MC_UU_00017/2 | Transfer | MC_UU_00017/1 | 31/03/2019 | 31/03/2024 | £2,644,000 |
MC_UU_00017/3 | Transfer | MC_UU_00017/2 | 31/03/2019 | 31/03/2024 | £3,269,000 |
MC_UU_00017/4 | Transfer | MC_UU_00017/3 | 31/03/2019 | 31/03/2024 | £1,831,000 |
MC_UU_00017/5 | Transfer | MC_UU_00017/4 | 31/03/2019 | 31/03/2024 | £2,183,000 |
Description | European Association of Preventive Cardiology (EAPC) |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Reviewer Scientific Abstracts |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | The World Heart Federation Reviewer for the Salim Yusuf Leadership Program applications |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Contribution to new or improved professional practice |
Description | Amazon Web Services Health Equity Initiative |
Amount | $208,750 (USD) |
Organisation | Amazon.com |
Department | Amazon Web Services |
Sector | Private |
Country | United States |
Start | 03/2023 |
End | 02/2024 |
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 |
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 | Collaborative publications |
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 collaboration |
Impact | Collaborative publications |
Start Year | 2020 |
Description | International Common Disease Alliance |
Organisation | International Common Disease Alliance |
Sector | Charity/Non Profit |
PI Contribution | MCPS is a partner |
Collaborator Contribution | Academic collaboration |
Impact | none yet |
Start Year | 2022 |
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 Epidemiology Unit |
Impact | none yet |
Start Year | 2022 |
Description | Mexico Biobank |
Organisation | Mexican Biobank |
Country | Mexico |
Sector | Charity/Non Profit |
PI Contribution | MCPS is a partner |
Collaborator Contribution | Academic collaboration |
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 | Various scientific publications |
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 | Scientific publications, such as the discovery of GPR75 as a novel target for 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 | Trans-ancestry meta-analysis improves performance of genetic scores for multiple adiposity-related traits in East Asian populations |
Organisation | University of Oxford |
Department | China Kadoorie Biobank |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | MCPS contributed summary statistics. |
Collaborator Contribution | academic partnership |
Impact | publication: https://doi.org/10.1101/2022.07.05.22277254 |
Start Year | 2022 |
Description | Appearance on UNAM-TV discussing the MCPS |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Appearance on UNAM-TV discussing the MCPS |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.youtube.com/watch?v=9ylITDT60xE |
Description | My First Grant: Introduction for Early-Career Researchers |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Other audiences |
Results and Impact | Event with presentations by experts with a panel discussion |
Year(s) Of Engagement Activity | 2022 |
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 |