B4140 - Estimating the causal effect of body mass index on platelet function - 08/09/2022

B number: 
Principal applicant name: 
Lucy Goudswaard | Population Health Sciences, University of Bristol (United Kingdom)
Professor Nicholas Timpson, Dr Laura Corbin, Professor Ingeborg Hers
Title of project: 
Estimating the causal effect of body mass index on platelet function
Proposal summary: 

Obesity is associated with an increased risk of arterial thrombosis, which results in heart attacks or stroke. Platelets are essential for haemostasis, however, in thrombosis platelets become hyper-activated. There is observational evidence that obesity is associated with platelet hyper-activation, but it is unknown whether the effect is causal. Within this project, I aim to use the largest cohort with platelet function and genetic data, the Framingham Heart Study (FHS), to interrogate this relationship. This will be coupled with the design and implementation of a recall study. Here, I aim to recall participants in the Avon Longitudinal Study of Parents And Children (ALSPAC) based on body mass index (BMI), including participants with variants of MC4R, a gene involved in energy homeostasis. A loss of function mutation has been shown to increase average fat mass by 15kg. As alleles are randomly assigned at conception, this variant should not be associated with confounding factors such as smoking habits. I will perform deep platelet phenotyping on participants (carriers and non-carriers of this variant), including electron microscopy and platelet proteomics to identify differences in platelet activation. These analyses will estimate whether BMI has a causal relationship with platelet function and may point towards mechanisms, which could refine antiplatelet treatment regimes in people with obesity.

Impact of research: 
To our knowledge, a recall study has not been performed to explore the effect of BMI on platelet function. The deep phenotypes that we will perform will complement our analyses using the Framingham Heart Study and will help us characterise the relationship between BMI and platelet function.
Date proposal received: 
Monday, 5 September, 2022
Date proposal approved: 
Monday, 5 September, 2022
Epidemiology, Obesity, Recall study Platelet function , Metabolic - metabolism