Award Title: Using genetics to understand changes in body weight over time and links to disease.
Funder: The Academy of Medical Sciences

Abstract: My research will go beyond existing studies to establish a better understanding of the relationship between weight fluctuation and diseases linked to obesity, including type 2 diabetes, cardiovascular disease, and stroke. Weight-fluctuations are common in people living with obesity. My project is important because I will assess the contribution of patterns of weight fluctuation derived from longitudinal population data. My project will be a major advance compared to previous studies that have focussed only on establishing links between one measure of weight and disease. 

I will perform four sets of analysis that address the following questions:
1)What patterns of weight fluctuation occur in a population setting?
2)How does pattern and severity of weight fluctuation correlate with disease risk and mortality?
3)Are there genetic factors associated with variability in weight fluctuation and do these differ from those associated with single time-point measures of weight?
4)Is weight fluctuation causal for disease when accounting for current BMI?

I will use primary care data, lifestyle data, and genetic data from 500,000 individuals from the UK Biobank, with follow-up in 23,000 individuals from the Women’s Genome Health Study. Analyses will focus on weight change prior to developing a disease based on longitudinal primary care data. 

The identification of causal associations between weight-fluctuation and disease will have important implications for public health strategies. For example, if “yoyo” weight trajectories are causally associated with increased disease risk, these findings may help inform future intervention strategies by targeting individuals who experience weight-cycling.

Lay Abstract: In the UK, over half of all adults are currently overweight, with £10 billion spent each year on treating diseases that are common in people living with obesity, such as type 2 diabetes. While previous research has focussed on links between weight and disease, less is known about the importance of weight-change over time. For example, one person’s weight may increase slowly while another person’s weight “yo-yos” up and down. The limited availability of data in large numbers of people means we know little about the link between weight fluctuation and disease that is independent from a single measure of a person’s weight.

My project is novel because I will combine people’s DNA data, health-care records, and lifestyle information to investigate weight-changes. I will test whether or not different patterns of weight-change make getting type 2 diabetes, for example, more likely, or whether simply being overweight is the main driver of increasing disease risk. My project is novel in scale – I will use information from 500,000 individuals that live in the UK. This data will be used to test 1) patterns of weight-change over time and links to disease, and 2) whether our DNA influences how much our weight changes over time.

If patterns of weight-change are found to increase disease risk, then this work may help healthcare professionals and patients understand the importance of weight-change. It will also inform future studies that aim to prevent groups of people at risk of developing disease, such as type 2 diabetes.

Research Activity Codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE