Understanding the role of fatty acids in the aetiology of cardiovascular disease using novel causal inference methods
Lead Research Organisation:
University of Bristol
Department Name: Social Medicine
Abstract
Despite efforts on prevention and treatment, cardiovascular disease is still a leading cause of death globally and in the UK. The World Health Organization emphasizes promoting healthy diets as a key factor to stem the alarming social and economic burden of cardiovascular disease. Since 1950s there is a widespread belief that the quantity and quality of dietary fat (fatty acids) are major triggers of cardiovascular disease, known as the 'diet-heart hypothesis'. However over the past few decades new research has challenged this prevailing idea. The current controversy surrounding health effects of fatty acids is partly driven by limitations of current studies. Studies of observational nature look for associations between people's diet and risk of cardiovascular disease, but cannot distinguish whether dietary fat is causally related to the disease or is just a bystander. Intervention studies usually have short duration and target very specific populations, and therefore also have limitations when interpreting long term effects of dietary fatty acids on the risk of developing cardiovascular disease in the general population.
I aim to embark on a four-year Medical Research Council funded programme at the University of Bristol to address the controversy surrounding fatty acids and cardiovascular health using innovative methods.
Blood levels of fatty acids are influenced by our genetic makeup. Individuals genetically predisposed to higher blood levels of certain fatty acids will have higher exposure to these nutrients throughout life. I will compare individuals with different genetic makeups related to blood levels of fatty acids using a technique named Mendelian randomisation to assess whether fatty acids directly cause cardiovascular disease (heart disease and stroke). In addition, I will use highly-detailed information on the biochemical constituents of blood (known as high throughput metabolomics) to understand precisely which mechanism could link fatty acids to cardiovascular disease. Finally, I will synthesise the available evidence on cardiovascular health effects of fatty acids in order to provide an overview of research findings and seek explanations for the potential inconsistencies regarding the 'diet-heart hypothesis'.
This type of research is only just becoming possible, due to a range of complementary factors. Firstly, advances in technology allowed scientists to measure millions of common between-individual differences in DNA sequence and to perform detailed biochemical measurement in the blood. Secondly, the proliferation of open access summary data from genetic studies and other initiatives, such as the UK Biobank, have yielded large-scale information on the relation between genetics and disease. Thirdly, the development of sophisticated statistical methods has allowed researchers to combine complex information on genetics, metabolism and health status. This fellowship takes advantage of all of these factors.
In summary, this project aims to produce world-leading research on the role of diet in health, particularly with regard to health effects of fatty acids, in order to better inform policy and care dedicated to cardiovascular disease prevention. Also, this research is likely to provide insights into cardiovascular disease mechanisms that may be useful to inform the design of new preventative drugs that would be helpful to the whole population, irrespective of their genetic makeup.
I aim to embark on a four-year Medical Research Council funded programme at the University of Bristol to address the controversy surrounding fatty acids and cardiovascular health using innovative methods.
Blood levels of fatty acids are influenced by our genetic makeup. Individuals genetically predisposed to higher blood levels of certain fatty acids will have higher exposure to these nutrients throughout life. I will compare individuals with different genetic makeups related to blood levels of fatty acids using a technique named Mendelian randomisation to assess whether fatty acids directly cause cardiovascular disease (heart disease and stroke). In addition, I will use highly-detailed information on the biochemical constituents of blood (known as high throughput metabolomics) to understand precisely which mechanism could link fatty acids to cardiovascular disease. Finally, I will synthesise the available evidence on cardiovascular health effects of fatty acids in order to provide an overview of research findings and seek explanations for the potential inconsistencies regarding the 'diet-heart hypothesis'.
This type of research is only just becoming possible, due to a range of complementary factors. Firstly, advances in technology allowed scientists to measure millions of common between-individual differences in DNA sequence and to perform detailed biochemical measurement in the blood. Secondly, the proliferation of open access summary data from genetic studies and other initiatives, such as the UK Biobank, have yielded large-scale information on the relation between genetics and disease. Thirdly, the development of sophisticated statistical methods has allowed researchers to combine complex information on genetics, metabolism and health status. This fellowship takes advantage of all of these factors.
In summary, this project aims to produce world-leading research on the role of diet in health, particularly with regard to health effects of fatty acids, in order to better inform policy and care dedicated to cardiovascular disease prevention. Also, this research is likely to provide insights into cardiovascular disease mechanisms that may be useful to inform the design of new preventative drugs that would be helpful to the whole population, irrespective of their genetic makeup.
Technical Summary
Aim: To assess whether fatty acids are involved in the aetiology of cardiovascular disease (CVD) and to identify potential underlying mechanisms.
Objectives:
1) To examine whether circulating fatty acids are causally related to CVD risk
2) To explore potential underlying mechanisms by which circulating fatty acids could be linked to CVD
3) To synthesize the literature on the relation between dietary fatty acids and CVD and extensively explore the presence and potential explanations of biases
Methodology: I will use data on genetic variants, fatty acids, other metabolites, and CVD (coronary artery disease and stroke) from UK Biobank and four study consortia (UCLEB, METASTROKE, CARDIoGRAMplusC4D, Metabolomics GWAS). The exposures of interest are fatty acids (saturated, monounsaturated, omega-3 and omega-6 fatty acids). To assess the potential causal effect of circulating fatty acids on CVD risk (Objective 1), genetic variants strongly associated with circulating free fatty acids will be used as instrumental variables in a Mendelian randomisation framework (n = 540,00-750,000 individuals). Causal mediation analysis will be used to better understand pathways by which fatty acids might be linked to CVD through a broad interrogation of various lipoproteins, lipids, and low molecular weight molecules that collectively constitute the metabolome (high throughput metabolomics profiling) (Objective 2). The literature on the association between dietary fatty acids and CVD will be appraised using novel techniques in meta-analytical research (overview of reviews and triangulation) aimed at providing an overview of the evidence and exploring the presence and reasons for potential biases (Objective 3).
Scientific and medical opportunities: My findings will provide important causal evidence regarding health effects of fatty acids that can be used to inform research, clinical practice and make appropriate public health policy.
Objectives:
1) To examine whether circulating fatty acids are causally related to CVD risk
2) To explore potential underlying mechanisms by which circulating fatty acids could be linked to CVD
3) To synthesize the literature on the relation between dietary fatty acids and CVD and extensively explore the presence and potential explanations of biases
Methodology: I will use data on genetic variants, fatty acids, other metabolites, and CVD (coronary artery disease and stroke) from UK Biobank and four study consortia (UCLEB, METASTROKE, CARDIoGRAMplusC4D, Metabolomics GWAS). The exposures of interest are fatty acids (saturated, monounsaturated, omega-3 and omega-6 fatty acids). To assess the potential causal effect of circulating fatty acids on CVD risk (Objective 1), genetic variants strongly associated with circulating free fatty acids will be used as instrumental variables in a Mendelian randomisation framework (n = 540,00-750,000 individuals). Causal mediation analysis will be used to better understand pathways by which fatty acids might be linked to CVD through a broad interrogation of various lipoproteins, lipids, and low molecular weight molecules that collectively constitute the metabolome (high throughput metabolomics profiling) (Objective 2). The literature on the association between dietary fatty acids and CVD will be appraised using novel techniques in meta-analytical research (overview of reviews and triangulation) aimed at providing an overview of the evidence and exploring the presence and reasons for potential biases (Objective 3).
Scientific and medical opportunities: My findings will provide important causal evidence regarding health effects of fatty acids that can be used to inform research, clinical practice and make appropriate public health policy.
Planned Impact
This work will appeal to a wide academic audience in the UK and internationally. The discussion on the role of dietary fat in cardiovascular disease ('diet-heart hypothesis') has divided academics for decades. Researchers within fields of nutrition, cardiovascular health, epidemiology, genetics, and public health will benefit from contributions this work will make to evidence base. Statisticians and epidemiologists may also benefit from the methodological insights which will be gained by the application of multiple techniques involving causal inference and evidence synthesis.
Research funding agencies from the UK and abroad are also potential beneficiaries. Despite the massive amount of resources invested in the field, the evidence base for the 'diet-heart hypothesis' is still a matter of heated debate. I propose to address this long-running scientific controversy using innovative approaches with data that have already been collected in order to greatly advance in our understanding of the health effects of fatty acids while maximising the resources currently available.
The findings of the proposed research will benefit a number of public sector organisations from UK and internationally. The findings will be directly relevant to the NHS and the Department of Health. Other national bodies such as Public Health England (PHE) would be able to use research outputs from this proposal. Part of their remit is to set the agenda for priorities in public health policy, and robust evidence on the health effects of fatty acids could be fed into policy at this level. The 2016 UK's national food guide, the Eatwell Guide, led by PHE, has eight core messages, three of which involve recommendations on dietary fat either directly (by promoting lower fat products, replacement of saturated by unsaturated fats or consumption of fish rich in omega-3 fatty acids) or indirectly (by recommending meals should be based on starchy foods). The promotion of dietary fat recommendations as a core component of food guides is a common feature among organization across the globe and, therefore, findings will be of widespread interest to international and global organizations. The Department of Chronic Disease and Health Promotion from World Health Organization (WHO) has as a top priority the implementation of the WHO Global Strategy on Diet, Physical Activity and Health and will also benefit from strengthening evidence base for dietary fatty acids recommendations.
My work is directly relevant to informing research agendas and work of charities, such as British Heart Foundation (BHF) and British Nutrition Foundation (BNF). For example, prevention of heart disease is a key feature of BHF research strategy and work in the wider community. In addition, translating and communicating complex scientific information on nutrition to the general public is a core purpose of BNF.
Advisory committees, such as the Scientific Advisory Committee in Nutrition (SACN), are also potential beneficiaries, particularly the SACN Saturated fats Working Group dedicated to review the evidence for the relationship between saturated fats and health and make recommendations.
My findings will also be of interest to health professionals providing dietary advice to patients and for the wider public which frequently faces difficulties when interpreting controversial findings from nutrition research.
Finally, there is likely to be a commercial interest in the research findings. Given that drug target validation has been identified as a key obstacle underlying the unsustainably high rate of drug development failure, the findings are likely to be of particular interest to the pharmaceutical industry.
The timescale for these benefits could be both within the lifetime of the fellowship, e.g. providing important aetiological insights for cardiovascular disease, or outside of the lifetime of the project, e.g. potential improvements in health policy and care influenced by these findings.
Research funding agencies from the UK and abroad are also potential beneficiaries. Despite the massive amount of resources invested in the field, the evidence base for the 'diet-heart hypothesis' is still a matter of heated debate. I propose to address this long-running scientific controversy using innovative approaches with data that have already been collected in order to greatly advance in our understanding of the health effects of fatty acids while maximising the resources currently available.
The findings of the proposed research will benefit a number of public sector organisations from UK and internationally. The findings will be directly relevant to the NHS and the Department of Health. Other national bodies such as Public Health England (PHE) would be able to use research outputs from this proposal. Part of their remit is to set the agenda for priorities in public health policy, and robust evidence on the health effects of fatty acids could be fed into policy at this level. The 2016 UK's national food guide, the Eatwell Guide, led by PHE, has eight core messages, three of which involve recommendations on dietary fat either directly (by promoting lower fat products, replacement of saturated by unsaturated fats or consumption of fish rich in omega-3 fatty acids) or indirectly (by recommending meals should be based on starchy foods). The promotion of dietary fat recommendations as a core component of food guides is a common feature among organization across the globe and, therefore, findings will be of widespread interest to international and global organizations. The Department of Chronic Disease and Health Promotion from World Health Organization (WHO) has as a top priority the implementation of the WHO Global Strategy on Diet, Physical Activity and Health and will also benefit from strengthening evidence base for dietary fatty acids recommendations.
My work is directly relevant to informing research agendas and work of charities, such as British Heart Foundation (BHF) and British Nutrition Foundation (BNF). For example, prevention of heart disease is a key feature of BHF research strategy and work in the wider community. In addition, translating and communicating complex scientific information on nutrition to the general public is a core purpose of BNF.
Advisory committees, such as the Scientific Advisory Committee in Nutrition (SACN), are also potential beneficiaries, particularly the SACN Saturated fats Working Group dedicated to review the evidence for the relationship between saturated fats and health and make recommendations.
My findings will also be of interest to health professionals providing dietary advice to patients and for the wider public which frequently faces difficulties when interpreting controversial findings from nutrition research.
Finally, there is likely to be a commercial interest in the research findings. Given that drug target validation has been identified as a key obstacle underlying the unsustainably high rate of drug development failure, the findings are likely to be of particular interest to the pharmaceutical industry.
The timescale for these benefits could be both within the lifetime of the fellowship, e.g. providing important aetiological insights for cardiovascular disease, or outside of the lifetime of the project, e.g. potential improvements in health policy and care influenced by these findings.
Organisations
- University of Bristol (Lead Research Organisation)
- University College London (Collaboration)
- Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE) (Collaboration)
- University of Groningen (Collaboration)
- Norwegian University of Science and Technology (NTNU) (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- UNIVERSITY OF EXETER (Collaboration)
- QUEEN MARY UNIVERSITY OF LONDON (Collaboration)
- Bradford Institute for Health Research (BIHR) (Collaboration)
- Vanderbilt University (Collaboration)
- Nightingale Health Ltd. (Collaboration)
- Norwegian Institute of Public Health (Collaboration)
- UNIVERSITY OF ESSEX (Collaboration)
- University of Bristol (Collaboration)
People |
ORCID iD |
Publications
Hartwig FP
(2017)
Inflammatory Biomarkers and Risk of Schizophrenia: A 2-Sample Mendelian Randomization Study.
in JAMA psychiatry
Borges MC
(2017)
Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis.
in Circulation. Cardiovascular genetics
Zheng J
(2017)
Recent Developments in Mendelian Randomization Studies.
in Current epidemiology reports
Lin B
(2018)
Mendelian Randomization Concerns
in JAMA Psychiatry
Au Yeung SL
(2018)
Association of Genetic Instrumental Variables for Lung Function on Coronary Artery Disease Risk: A 2-Sample Mendelian Randomization Study.
in Circulation. Genomic and precision medicine
Hartwig FP
(2018)
Letter by Hartwig et al Regarding Article, "Evaluation of the Pleiotropic Effects of Statins: A Reanalysis of the Randomized Trial Evidence Using Egger Regression".
in Arteriosclerosis, thrombosis, and vascular biology
Hartwig F
(2018)
Mendelian Randomization Concerns-Reply
in JAMA Psychiatry
Liu X
(2019)
Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.
in Nature communications
De Silva NMG
(2019)
Liver Function and Risk of Type 2 Diabetes: Bidirectional Mendelian Randomization Study.
in Diabetes
Description | Mendelian randomization studies of metabolites on heart failure |
Amount | ฿539,000 (THB) |
Organisation | Thailand Research Fund |
Sector | Public |
Country | Thailand |
Start |
Description | SSCM conference fund scheme |
Amount | £500 (GBP) |
Organisation | University of Bristol |
Sector | Academic/University |
Country | United Kingdom |
Start | 07/2017 |
End | 08/2017 |
Description | University Cancer Research Fund |
Amount | £4,997 (GBP) |
Organisation | University of Bristol |
Sector | Academic/University |
Country | United Kingdom |
Start | 08/2021 |
Title | GWAS of NMR metabolites in ~150,000 UK Biobank participants |
Description | I have generated and made available publicly available metadata for GWASes of > 200 metabolites via the MRC IEU Open GWAS platform, as a result of the collaboration with Nightingale Health and UK Biobank listed in "Collaborations". |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | The metadata is being used by several academics internal and external to the University of Bristol, as well as researchers from the International Agency for Cancer Research (IARC). |
URL | https://gwas.mrcieu.ac.uk/ |
Description | CHARGE consortium - Cross-platform metabolomics GWAS |
Organisation | Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE) |
Country | Global |
Sector | Academic/University |
PI Contribution | I am contributing to designing the study and analysing data. |
Collaborator Contribution | The CHARGE Metabolomics Working Group is responsible for planning, conducting and reporting this large ongoing collaborative effort. |
Impact | Meta-analysis of genome-wide association studies on human metabolome. This collaboration was multi-disciplinary, involving statisticians, genetic epidemiologists, epidemiologists and clinicians. |
Start Year | 2019 |
Description | EBI Mechanisms to Populations research strand |
Organisation | University of Bristol |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This research strand is a cross-faculty initiative that brings together an interdisciplinary community of researchers enabling a greater understanding of the complexity of human disease. |
Collaborator Contribution | I am a member of the steering committee |
Impact | The collaboration includes multiple faculties in the University of Bristol spanning the space between Fundamental Bioscience and Population Health Science. |
Start Year | 2020 |
Description | IPD meta-analysis on the association of blood fatty acids and cardiometabolic diseases |
Organisation | University College London |
Department | Department of Primary Care & Population Sciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I have led this individual participant meta-analysis on the association of circulating fatty acids with cardiometabolic diseases. |
Collaborator Contribution | Collaborators participated in designing the study, provided data and critically revised the manuscript. |
Impact | Borges et al. (2019). Circulating Fatty Acids and Risk of Coronary Heart Disease and Stroke: Individual Participant Data Meta-Analysis in Up to 16 126 Participants. J Am Heart Assoc. 2020 Mar 3;9(5):e013131. doi: 10.1161/JAHA.119.013131. |
Start Year | 2017 |
Description | IPD meta-analysis on the association of blood fatty acids and cardiometabolic diseases |
Organisation | University College London |
Department | Institute for Women's Health |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I have led this individual participant meta-analysis on the association of circulating fatty acids with cardiometabolic diseases. |
Collaborator Contribution | Collaborators participated in designing the study, provided data and critically revised the manuscript. |
Impact | Borges et al. (2019). Circulating Fatty Acids and Risk of Coronary Heart Disease and Stroke: Individual Participant Data Meta-Analysis in Up to 16 126 Participants. J Am Heart Assoc. 2020 Mar 3;9(5):e013131. doi: 10.1161/JAHA.119.013131. |
Start Year | 2017 |
Description | IPD meta-analysis on the association of blood fatty acids and cardiometabolic diseases |
Organisation | University College London |
Department | Institute of Cardiovascular Science |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I have led this individual participant meta-analysis on the association of circulating fatty acids with cardiometabolic diseases. |
Collaborator Contribution | Collaborators participated in designing the study, provided data and critically revised the manuscript. |
Impact | Borges et al. (2019). Circulating Fatty Acids and Risk of Coronary Heart Disease and Stroke: Individual Participant Data Meta-Analysis in Up to 16 126 Participants. J Am Heart Assoc. 2020 Mar 3;9(5):e013131. doi: 10.1161/JAHA.119.013131. |
Start Year | 2017 |
Description | IPD meta-analysis on the association of blood fatty acids and cardiometabolic diseases |
Organisation | University College London |
Department | Institute of Health Informatics |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I have led this individual participant meta-analysis on the association of circulating fatty acids with cardiometabolic diseases. |
Collaborator Contribution | Collaborators participated in designing the study, provided data and critically revised the manuscript. |
Impact | Borges et al. (2019). Circulating Fatty Acids and Risk of Coronary Heart Disease and Stroke: Individual Participant Data Meta-Analysis in Up to 16 126 Participants. J Am Heart Assoc. 2020 Mar 3;9(5):e013131. doi: 10.1161/JAHA.119.013131. |
Start Year | 2017 |
Description | IPD meta-analysis on the association of blood fatty acids and cardiometabolic diseases |
Organisation | University College London |
Department | Research Department of Epidemiology and Public Health |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I have led this individual participant meta-analysis on the association of circulating fatty acids with cardiometabolic diseases. |
Collaborator Contribution | Collaborators participated in designing the study, provided data and critically revised the manuscript. |
Impact | Borges et al. (2019). Circulating Fatty Acids and Risk of Coronary Heart Disease and Stroke: Individual Participant Data Meta-Analysis in Up to 16 126 Participants. J Am Heart Assoc. 2020 Mar 3;9(5):e013131. doi: 10.1161/JAHA.119.013131. |
Start Year | 2017 |
Description | IPD meta-analysis on the association of blood fatty acids and cardiometabolic diseases |
Organisation | University of Essex |
Department | Institute for Social and Economic Research, Essex |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I have led this individual participant meta-analysis on the association of circulating fatty acids with cardiometabolic diseases. |
Collaborator Contribution | Collaborators participated in designing the study, provided data and critically revised the manuscript. |
Impact | Borges et al. (2019). Circulating Fatty Acids and Risk of Coronary Heart Disease and Stroke: Individual Participant Data Meta-Analysis in Up to 16 126 Participants. J Am Heart Assoc. 2020 Mar 3;9(5):e013131. doi: 10.1161/JAHA.119.013131. |
Start Year | 2017 |
Description | IPD meta-analysis on the association of blood fatty acids and cardiometabolic diseases |
Organisation | University of Groningen |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | I have led this individual participant meta-analysis on the association of circulating fatty acids with cardiometabolic diseases. |
Collaborator Contribution | Collaborators participated in designing the study, provided data and critically revised the manuscript. |
Impact | Borges et al. (2019). Circulating Fatty Acids and Risk of Coronary Heart Disease and Stroke: Individual Participant Data Meta-Analysis in Up to 16 126 Participants. J Am Heart Assoc. 2020 Mar 3;9(5):e013131. doi: 10.1161/JAHA.119.013131. |
Start Year | 2017 |
Description | MR-PREG - Mendelian Randomization to assess PREGnancy risk factors |
Organisation | Bradford Institute for Health Research (BIHR) |
Department | Born in Bradford |
Country | United Kingdom |
Sector | Public |
PI Contribution | I am leading this initiative with Prof. Deborah Lawlor. |
Collaborator Contribution | Partners have contributed with scientific content, data and analytical capacity |
Impact | Borges MC, et al. Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes. BMC Med. 2024 Jan 29;22(1):32. Taylor K, [7 additional authors], Borges MC, Caputo M, Lawlor DA. The effect of maternal BMI, smoking and alcohol on congenital heart diseases: a Mendelian randomisation study. BMC Med. 2023;21(1):35. Zhao J, [10 additional authors], Lawlor DA, Borges MC; MR-PREG Consortium. Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study. EBioMedicine. 2023 Feb;88:104441 Yang Q, [11 additional authors], Borges MC. Investigating causal relations between sleep duration and risks of adverse pregnancy and perinatal outcomes: linear and nonlinear Mendelian randomization analyses. BMC Med. 2022 Sep 12;20(1):295. Yang Q, Borges MC, et al. Associations between insomnia and pregnancy and perinatal outcomes: Evidence from mendelian randomization and multivariable regression analyses. PLoS Med. 2022;19(9):e1004090. Taylor K, [9 additional authors], Borges MC, Caputo M, Lawlor DA. The Relationship of Maternal Gestational Mass Spectrometry-Derived Metabolites with Offspring Congenital Heart Disease: Results from Multivariable and Mendelian Randomization Analyses. J Cardiovasc Dev Dis. 2022;9(8):237. Brito Nunes C, [5 additional authors], Borges MC, Lawlor DA, Warrington NM, Evans DM, Hwang LD, Moen GH. Mendelian randomization study of maternal coffee consumption and its influence on birthweight, stillbirth, miscarriage, gestational age and pre-term birth. Int J Epidemiol. 2023;52(1):165-177. Bond TA, [3 additional authors], Borges MC, et al. Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores. BMC Med. 2022;20(1):34. |
Start Year | 2018 |
Description | MR-PREG - Mendelian Randomization to assess PREGnancy risk factors |
Organisation | Norwegian Institute of Public Health |
Country | Norway |
Sector | Public |
PI Contribution | I am leading this initiative with Prof. Deborah Lawlor. |
Collaborator Contribution | Partners have contributed with scientific content, data and analytical capacity |
Impact | Borges MC, et al. Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes. BMC Med. 2024 Jan 29;22(1):32. Taylor K, [7 additional authors], Borges MC, Caputo M, Lawlor DA. The effect of maternal BMI, smoking and alcohol on congenital heart diseases: a Mendelian randomisation study. BMC Med. 2023;21(1):35. Zhao J, [10 additional authors], Lawlor DA, Borges MC; MR-PREG Consortium. Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study. EBioMedicine. 2023 Feb;88:104441 Yang Q, [11 additional authors], Borges MC. Investigating causal relations between sleep duration and risks of adverse pregnancy and perinatal outcomes: linear and nonlinear Mendelian randomization analyses. BMC Med. 2022 Sep 12;20(1):295. Yang Q, Borges MC, et al. Associations between insomnia and pregnancy and perinatal outcomes: Evidence from mendelian randomization and multivariable regression analyses. PLoS Med. 2022;19(9):e1004090. Taylor K, [9 additional authors], Borges MC, Caputo M, Lawlor DA. The Relationship of Maternal Gestational Mass Spectrometry-Derived Metabolites with Offspring Congenital Heart Disease: Results from Multivariable and Mendelian Randomization Analyses. J Cardiovasc Dev Dis. 2022;9(8):237. Brito Nunes C, [5 additional authors], Borges MC, Lawlor DA, Warrington NM, Evans DM, Hwang LD, Moen GH. Mendelian randomization study of maternal coffee consumption and its influence on birthweight, stillbirth, miscarriage, gestational age and pre-term birth. Int J Epidemiol. 2023;52(1):165-177. Bond TA, [3 additional authors], Borges MC, et al. Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores. BMC Med. 2022;20(1):34. |
Start Year | 2018 |
Description | MR-PREG - Mendelian Randomization to assess PREGnancy risk factors |
Organisation | Norwegian University of Science and Technology (NTNU) |
Department | Department of Public Health and Nursing |
Country | Norway |
Sector | Academic/University |
PI Contribution | I am leading this initiative with Prof. Deborah Lawlor. |
Collaborator Contribution | Partners have contributed with scientific content, data and analytical capacity |
Impact | Borges MC, et al. Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes. BMC Med. 2024 Jan 29;22(1):32. Taylor K, [7 additional authors], Borges MC, Caputo M, Lawlor DA. The effect of maternal BMI, smoking and alcohol on congenital heart diseases: a Mendelian randomisation study. BMC Med. 2023;21(1):35. Zhao J, [10 additional authors], Lawlor DA, Borges MC; MR-PREG Consortium. Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study. EBioMedicine. 2023 Feb;88:104441 Yang Q, [11 additional authors], Borges MC. Investigating causal relations between sleep duration and risks of adverse pregnancy and perinatal outcomes: linear and nonlinear Mendelian randomization analyses. BMC Med. 2022 Sep 12;20(1):295. Yang Q, Borges MC, et al. Associations between insomnia and pregnancy and perinatal outcomes: Evidence from mendelian randomization and multivariable regression analyses. PLoS Med. 2022;19(9):e1004090. Taylor K, [9 additional authors], Borges MC, Caputo M, Lawlor DA. The Relationship of Maternal Gestational Mass Spectrometry-Derived Metabolites with Offspring Congenital Heart Disease: Results from Multivariable and Mendelian Randomization Analyses. J Cardiovasc Dev Dis. 2022;9(8):237. Brito Nunes C, [5 additional authors], Borges MC, Lawlor DA, Warrington NM, Evans DM, Hwang LD, Moen GH. Mendelian randomization study of maternal coffee consumption and its influence on birthweight, stillbirth, miscarriage, gestational age and pre-term birth. Int J Epidemiol. 2023;52(1):165-177. Bond TA, [3 additional authors], Borges MC, et al. Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores. BMC Med. 2022;20(1):34. |
Start Year | 2018 |
Description | MR-PREG - Mendelian Randomization to assess PREGnancy risk factors |
Organisation | University of Exeter |
Department | Medical School |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I am leading this initiative with Prof. Deborah Lawlor. |
Collaborator Contribution | Partners have contributed with scientific content, data and analytical capacity |
Impact | Borges MC, et al. Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes. BMC Med. 2024 Jan 29;22(1):32. Taylor K, [7 additional authors], Borges MC, Caputo M, Lawlor DA. The effect of maternal BMI, smoking and alcohol on congenital heart diseases: a Mendelian randomisation study. BMC Med. 2023;21(1):35. Zhao J, [10 additional authors], Lawlor DA, Borges MC; MR-PREG Consortium. Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study. EBioMedicine. 2023 Feb;88:104441 Yang Q, [11 additional authors], Borges MC. Investigating causal relations between sleep duration and risks of adverse pregnancy and perinatal outcomes: linear and nonlinear Mendelian randomization analyses. BMC Med. 2022 Sep 12;20(1):295. Yang Q, Borges MC, et al. Associations between insomnia and pregnancy and perinatal outcomes: Evidence from mendelian randomization and multivariable regression analyses. PLoS Med. 2022;19(9):e1004090. Taylor K, [9 additional authors], Borges MC, Caputo M, Lawlor DA. The Relationship of Maternal Gestational Mass Spectrometry-Derived Metabolites with Offspring Congenital Heart Disease: Results from Multivariable and Mendelian Randomization Analyses. J Cardiovasc Dev Dis. 2022;9(8):237. Brito Nunes C, [5 additional authors], Borges MC, Lawlor DA, Warrington NM, Evans DM, Hwang LD, Moen GH. Mendelian randomization study of maternal coffee consumption and its influence on birthweight, stillbirth, miscarriage, gestational age and pre-term birth. Int J Epidemiol. 2023;52(1):165-177. Bond TA, [3 additional authors], Borges MC, et al. Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores. BMC Med. 2022;20(1):34. |
Start Year | 2018 |
Description | Mendelian randomization and fatty acids working group |
Organisation | Queen Mary University of London |
Department | Wolfson Institute of Preventive Medicine |
Country | United Kingdom |
Sector | Public |
PI Contribution | I have led this initiative together with other member of my Unit (MRC Integrative Epidemiology Unit, University of Bristol). |
Collaborator Contribution | My partners are leading the work package on cancer, multiple sclerosis and eczema. |
Impact | Khankari NK et al. Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2020 Feb 12. pii: cebp.0891.2019. doi: 10.1158/1055-9965.EPI-19-0891. Jones HJ, Borges MC, et al. Associations between plasma fatty acid concentrations and schizophrenia: a two-sample Mendelian randomisation study. Lancet Psychiatry. 2021 Dec;8(12):1062-1070. doi: 10.1016/S2215-0366(21)00286-8. Borges MC, Haycock PC, Zheng J, Hemani G, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA. Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants. BMC Med. 2022 Jun 13;20(1):210. doi: 10.1186/s12916-022-02399-w. PMID: 35692035; PMCID: PMC9190170. Borges MC, Haycock P, Zheng J, Hemani G, Howe LJ, Schmidt AF, Staley JR, Lumbers RT, Henry A, Lemaitre RN, Gaunt TR, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA. The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study. Hum Mol Genet. 2022 Nov 28;31(23):4034-4054. doi: 10.1093/hmg/ddac153. PMID: 35796550; PMCID: PMC9703943. Haycock PC, Borges MC, Burrows K, Lemaitre RN, Burgess S, Khankari NK, Tsilidis KK, Gaunt TR, Hemani G, Zheng J, Truong T, Birmann BM, OMara T, Spurdle AB, Iles MM, Law MH, Slager SL, Saberi Hosnijeh F, Mariosa D, Cotterchio M, Cerhan JR, Peters U, Enroth S, Gharahkhani P, Le Marchand L, Williams AC, Block RC; ACCC; CCFR-CORECT-GECCO; EPITHYR; InterLymph; MMAC; ECAC; ILCCO; PRACTICAL Consortium; PanScan; PanC4; Amos CI, Hung RJ, Zheng W, Gunter MJ, Smith GD, Relton C, Martin RM; Fatty Acids in Cancer Mendelian Randomization Collaboration. The association between genetically elevated polyunsaturated fatty acids and risk of cancer. EBioMedicine. 2023 May;91:104510. doi: 10.1016/j.ebiom.2023.104510. Epub 2023 Apr 20. PMID: 37086649; PMCID: PMC10148095. Hu C, Zhou Y, Wu X, Jia X, Zhu Y, Zheng R, Wang S, Lin L, Qi H, Lin H, Li M, Wang T, Zhao Z, Xu M, Xu Y, Chen Y, Ning G, Borges MC, Wang W, Zheng J, Bi Y, Lu J. Evaluating the distinct pleiotropic effects of omega-3 fatty acids on type 2 diabetes mellitus: a mendelian randomization study. J Transl Med. 2023 Jun 7;21(1):370. doi: 10.1186/s12967-023-04202-7. PMID: 37286992; PMCID: PMC10249205. |
Start Year | 2018 |
Description | Mendelian randomization and fatty acids working group |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I have led this initiative together with other member of my Unit (MRC Integrative Epidemiology Unit, University of Bristol). |
Collaborator Contribution | My partners are leading the work package on cancer, multiple sclerosis and eczema. |
Impact | Khankari NK et al. Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2020 Feb 12. pii: cebp.0891.2019. doi: 10.1158/1055-9965.EPI-19-0891. Jones HJ, Borges MC, et al. Associations between plasma fatty acid concentrations and schizophrenia: a two-sample Mendelian randomisation study. Lancet Psychiatry. 2021 Dec;8(12):1062-1070. doi: 10.1016/S2215-0366(21)00286-8. Borges MC, Haycock PC, Zheng J, Hemani G, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA. Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants. BMC Med. 2022 Jun 13;20(1):210. doi: 10.1186/s12916-022-02399-w. PMID: 35692035; PMCID: PMC9190170. Borges MC, Haycock P, Zheng J, Hemani G, Howe LJ, Schmidt AF, Staley JR, Lumbers RT, Henry A, Lemaitre RN, Gaunt TR, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA. The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study. Hum Mol Genet. 2022 Nov 28;31(23):4034-4054. doi: 10.1093/hmg/ddac153. PMID: 35796550; PMCID: PMC9703943. Haycock PC, Borges MC, Burrows K, Lemaitre RN, Burgess S, Khankari NK, Tsilidis KK, Gaunt TR, Hemani G, Zheng J, Truong T, Birmann BM, OMara T, Spurdle AB, Iles MM, Law MH, Slager SL, Saberi Hosnijeh F, Mariosa D, Cotterchio M, Cerhan JR, Peters U, Enroth S, Gharahkhani P, Le Marchand L, Williams AC, Block RC; ACCC; CCFR-CORECT-GECCO; EPITHYR; InterLymph; MMAC; ECAC; ILCCO; PRACTICAL Consortium; PanScan; PanC4; Amos CI, Hung RJ, Zheng W, Gunter MJ, Smith GD, Relton C, Martin RM; Fatty Acids in Cancer Mendelian Randomization Collaboration. The association between genetically elevated polyunsaturated fatty acids and risk of cancer. EBioMedicine. 2023 May;91:104510. doi: 10.1016/j.ebiom.2023.104510. Epub 2023 Apr 20. PMID: 37086649; PMCID: PMC10148095. Hu C, Zhou Y, Wu X, Jia X, Zhu Y, Zheng R, Wang S, Lin L, Qi H, Lin H, Li M, Wang T, Zhao Z, Xu M, Xu Y, Chen Y, Ning G, Borges MC, Wang W, Zheng J, Bi Y, Lu J. Evaluating the distinct pleiotropic effects of omega-3 fatty acids on type 2 diabetes mellitus: a mendelian randomization study. J Transl Med. 2023 Jun 7;21(1):370. doi: 10.1186/s12967-023-04202-7. PMID: 37286992; PMCID: PMC10249205. |
Start Year | 2018 |
Description | Mendelian randomization and fatty acids working group |
Organisation | University of Cambridge |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I have led this initiative together with other member of my Unit (MRC Integrative Epidemiology Unit, University of Bristol). |
Collaborator Contribution | My partners are leading the work package on cancer, multiple sclerosis and eczema. |
Impact | Khankari NK et al. Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2020 Feb 12. pii: cebp.0891.2019. doi: 10.1158/1055-9965.EPI-19-0891. Jones HJ, Borges MC, et al. Associations between plasma fatty acid concentrations and schizophrenia: a two-sample Mendelian randomisation study. Lancet Psychiatry. 2021 Dec;8(12):1062-1070. doi: 10.1016/S2215-0366(21)00286-8. Borges MC, Haycock PC, Zheng J, Hemani G, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA. Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants. BMC Med. 2022 Jun 13;20(1):210. doi: 10.1186/s12916-022-02399-w. PMID: 35692035; PMCID: PMC9190170. Borges MC, Haycock P, Zheng J, Hemani G, Howe LJ, Schmidt AF, Staley JR, Lumbers RT, Henry A, Lemaitre RN, Gaunt TR, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA. The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study. Hum Mol Genet. 2022 Nov 28;31(23):4034-4054. doi: 10.1093/hmg/ddac153. PMID: 35796550; PMCID: PMC9703943. Haycock PC, Borges MC, Burrows K, Lemaitre RN, Burgess S, Khankari NK, Tsilidis KK, Gaunt TR, Hemani G, Zheng J, Truong T, Birmann BM, OMara T, Spurdle AB, Iles MM, Law MH, Slager SL, Saberi Hosnijeh F, Mariosa D, Cotterchio M, Cerhan JR, Peters U, Enroth S, Gharahkhani P, Le Marchand L, Williams AC, Block RC; ACCC; CCFR-CORECT-GECCO; EPITHYR; InterLymph; MMAC; ECAC; ILCCO; PRACTICAL Consortium; PanScan; PanC4; Amos CI, Hung RJ, Zheng W, Gunter MJ, Smith GD, Relton C, Martin RM; Fatty Acids in Cancer Mendelian Randomization Collaboration. The association between genetically elevated polyunsaturated fatty acids and risk of cancer. EBioMedicine. 2023 May;91:104510. doi: 10.1016/j.ebiom.2023.104510. Epub 2023 Apr 20. PMID: 37086649; PMCID: PMC10148095. Hu C, Zhou Y, Wu X, Jia X, Zhu Y, Zheng R, Wang S, Lin L, Qi H, Lin H, Li M, Wang T, Zhao Z, Xu M, Xu Y, Chen Y, Ning G, Borges MC, Wang W, Zheng J, Bi Y, Lu J. Evaluating the distinct pleiotropic effects of omega-3 fatty acids on type 2 diabetes mellitus: a mendelian randomization study. J Transl Med. 2023 Jun 7;21(1):370. doi: 10.1186/s12967-023-04202-7. PMID: 37286992; PMCID: PMC10249205. |
Start Year | 2018 |
Description | Mendelian randomization and fatty acids working group |
Organisation | Vanderbilt University |
Department | Vanderbilt Medical Center |
Country | United States |
Sector | Academic/University |
PI Contribution | I have led this initiative together with other member of my Unit (MRC Integrative Epidemiology Unit, University of Bristol). |
Collaborator Contribution | My partners are leading the work package on cancer, multiple sclerosis and eczema. |
Impact | Khankari NK et al. Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2020 Feb 12. pii: cebp.0891.2019. doi: 10.1158/1055-9965.EPI-19-0891. Jones HJ, Borges MC, et al. Associations between plasma fatty acid concentrations and schizophrenia: a two-sample Mendelian randomisation study. Lancet Psychiatry. 2021 Dec;8(12):1062-1070. doi: 10.1016/S2215-0366(21)00286-8. Borges MC, Haycock PC, Zheng J, Hemani G, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA. Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants. BMC Med. 2022 Jun 13;20(1):210. doi: 10.1186/s12916-022-02399-w. PMID: 35692035; PMCID: PMC9190170. Borges MC, Haycock P, Zheng J, Hemani G, Howe LJ, Schmidt AF, Staley JR, Lumbers RT, Henry A, Lemaitre RN, Gaunt TR, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA. The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study. Hum Mol Genet. 2022 Nov 28;31(23):4034-4054. doi: 10.1093/hmg/ddac153. PMID: 35796550; PMCID: PMC9703943. Haycock PC, Borges MC, Burrows K, Lemaitre RN, Burgess S, Khankari NK, Tsilidis KK, Gaunt TR, Hemani G, Zheng J, Truong T, Birmann BM, OMara T, Spurdle AB, Iles MM, Law MH, Slager SL, Saberi Hosnijeh F, Mariosa D, Cotterchio M, Cerhan JR, Peters U, Enroth S, Gharahkhani P, Le Marchand L, Williams AC, Block RC; ACCC; CCFR-CORECT-GECCO; EPITHYR; InterLymph; MMAC; ECAC; ILCCO; PRACTICAL Consortium; PanScan; PanC4; Amos CI, Hung RJ, Zheng W, Gunter MJ, Smith GD, Relton C, Martin RM; Fatty Acids in Cancer Mendelian Randomization Collaboration. The association between genetically elevated polyunsaturated fatty acids and risk of cancer. EBioMedicine. 2023 May;91:104510. doi: 10.1016/j.ebiom.2023.104510. Epub 2023 Apr 20. PMID: 37086649; PMCID: PMC10148095. Hu C, Zhou Y, Wu X, Jia X, Zhu Y, Zheng R, Wang S, Lin L, Qi H, Lin H, Li M, Wang T, Zhao Z, Xu M, Xu Y, Chen Y, Ning G, Borges MC, Wang W, Zheng J, Bi Y, Lu J. Evaluating the distinct pleiotropic effects of omega-3 fatty acids on type 2 diabetes mellitus: a mendelian randomization study. J Transl Med. 2023 Jun 7;21(1):370. doi: 10.1186/s12967-023-04202-7. PMID: 37286992; PMCID: PMC10249205. |
Start Year | 2018 |
Description | Nightingale Health - UK Biobank collaboration |
Organisation | Nightingale Health Ltd. |
Country | Finland |
Sector | Private |
PI Contribution | I was invited by Nightingale Health Ltd to propose and conduct research on the first ~120,000 UK Biobank samples with Nightingale metabolomics data. I have conducted GWAS analyses on 249 metabolomic measure and made the data available for the scientific community via the IEU Open GWAS platform (https://gwas.mrcieu.ac.uk/). |
Collaborator Contribution | Nightingale Health Ltd and UK Biobank provided the NMR metabolomics data. |
Impact | The collaboration has resulted in two papers, one published in BMC Medicine (PMID: 35692035) and another in Nature Communications (PMID: 38320991). We have recently renewed the collaboration for the analyses of metabolomics data from the full sample of UK Biobank (N ~ 500,000). |
Start Year | 2020 |
Description | IGES 2019 Education Workshop: Introduction to Mendelian randomization |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | This pre-conference workshop took place in Houston, US, as part of the activities of the 2019 IGES (ie International Genetic Epidemiology Society) conference. I was involved in teaching and facilitating practical activities aimed at providing an introduction to the conduct, assumptions, strengths and limitations of Mendelian randomization. The workshop targeted academics from different backgrounds, level of experience and nationalities. |
Year(s) Of Engagement Activity | 2019 |
URL | https://iges.memberclicks.net/education-workshop |
Description | MR in Nutrition and Cancer Workshop: "What are the challenges in nutritional cancer epidemiology and how can Mendelian randomization address them?" |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | I helped organising a two-day workshop to showcase the development, application and translation of Mendelian randomization methods to nutrition and cancer research. This is a complex and novel area that would benefit substantially from that application of causal inference methods. The key aims of the meeting were to discuss methodological and conceptual challenges with exemplary case studies, whilst identifying potential solutions to arising limitations. |
Year(s) Of Engagement Activity | 2019 |
Description | Visit to International Agency for Research on Cancer (IARC), World Health Organization (WHO) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | IARC organised several research meetings to discuss how the methods I am applying in my fellowship could be used to support their work. In particular, these meetings focused on how to better address methodological challenges on improving causal inference on the identification of modifiable causes of cancer. I was also invited to give a seminar on "Challenges and opportunities of using Mendelian randomization to unravel molecular mechanisms of complex diseases and developmental origins of disease". This visit helped establishing/strengthening collaborations on ongoing projects and discussing ideas for future collaborative work. |
Year(s) Of Engagement Activity | 2019 |