| Application: | 16729, MR-PheWAS: hypothesis prioritization among potential causal effects of body mass index on many outcomes with Mendelian randomisation, using 500K participants of the UK biobank |
| Title: | Evaluation of the causal effects between subjective wellbeing and cardiometabolic health: mendelian randomisation study |
| Size: | 229814 B |
| Archived: | 2 Nov 2020 |
| Stability: | Complete |
| Personal: | No individual-level data |
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Notes
This study explored the impact of our physical health, such as body weight, heart health and blood pressure, to see whether individuals with poorer physical health went on to be less happy and less satisfied with their lives.Using a technique called Mendelian randomization, we asked whether poorer physical health causes lower mental wellbeing, or whether individuals with lower mental wellbeing are more likely to go on to have later problems with their physical health. This technique provides evidence of the direction of causation by using genetic variants that have been associated with physical health and mental wellbeing. We tested 11 measures of physical health including coronary artery disease, heart attack, cholesterol, blood pressure, body fat and Body Mass Index (BMI).
Results suggested a consistent causal effect of higher BMI on lower mental wellbeing. There was little evidence that the other physical health traits were leading to less happiness and life satisfaction. The same pattern of results was seen in a follow-up analysis using the UK Biobank where we were able to look at different aspects of life satisfaction and found that the key impact of higher BMI was on lower satisfaction with health. We also showed that the effect is present from age 40 through to age 70, and in both men and women. When testing whether mental wellbeing caused any of these physical health traits, we found little evidence for a causal impact in that direction, but this analysis is limited because there are so far fewer genetic variants for mental wellbeing. As we uncover more of the genetic variants associated with mental health traits, we will be able to test this direction of effects more thoroughly.
Application 16729
MR-PheWAS: hypothesis prioritization among potential causal effects of body mass index on many outcomes with Mendelian randomisation, using 500K participants of the UK biobank
We aim to test a novel method for identifying potentially causal associations, which we call the Mendelian randomisation phenome-wide association study (MR-pheWAS) approach. We aim to identify potentially causal effects of BMI, as an exemplar. We have tested the MR-pheWAS approach using the Avon Longitudinal Study of Parents and Children (ALSPAC) dataset (with ~8K participants). Repeating this with Biobank will greatly improve statistical power, and means we investigate causal effects in adulthood. Research question: What novel, potentially causal effects of BMI can the MR-pheWAS approach identify? Health conditions: Body mass index, and several other traits. BMI is associated with a wide range of diseases. This project aims to improve understanding of the complex effects of BMI, by testing for the causal effects of BMI on a wide range of outcomes. Results from this project will prioritize a subset of hypotheses for replication and further investigation. Identifying potentially causal effects of BMI is important in order to inform policy makers on appropriate interventions. Interventions targeted at BMI are likely to impact a wide range of traits and diseases. This is becoming increasingly important as the UK is now experiencing increasing levels of obesity. We will use data of all participants from Biobank that have measurements for BMI and a set of genetic loci that have previously been found to be associated with BMI. We will test the causal effect of BMI on a wide range of outcomes. We will do this using a natural experiment (instrumental variable) constructed from the genome (a Mendelian randomization approach), to identify outcomes that may be affected by BMI. We use a hypothesis-free approach and so will test a large arbitrarily selected set of outcomes, rather than selecting particular outcomes. All participants with a value for BMI (var=21001) and BMI associated genetic loci.
| Lead investigator: | Dr Louise Millard |
| Lead institution: | University of Bristol |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 2740 | Evaluation of the causal effects between subjective wellbeing and cardiometabolic health: mendelian randomisation study | Wootton RE et al. | 2018 | BMJ |
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