B3230 - Characterisation of childhood and adolescent favourable adiposity alleles identifed in adults - 18/12/2018

B number: 
B3230
Principal applicant name: 
Tim Frayling | University of Exeter (UK)
Co-applicants: 
Prof Nic Timpson, Dr Kaitlin Wade, Dr Joshua Bell, Dr Emma Vincent, Matthew Lee, Prof George Davey Smith, Dr Hanieh Yaghootkar, Dr Jess Tyrrell
Title of project: 
Characterisation of childhood and adolescent "favourable adiposity" alleles identifed in adults
Proposal summary: 

We would like to access the Children of the 90s and their parents’ genetic data and some imaging and blood biomarker information in order to characterise “favourable adiposity” genes. By this we mean versions of genes (alleles) that result in a higher BMI and body fat but lower risk of diseases such as type 2 diabetes, hypertension and heart disease. Current studies have already identified 14 alleles associated with higher body fat % but lower risk of these diseases. We know that some of these “favourable adiposity” genes operate by putting more fat in the lower body, resulting in a lower waist to hip ratio (“pear” rather than “apple” shape) in women. Using MRI imaging from adults, we know that these alleles add more fat under the skin (subcutaneous) but less fat to the liver. These genes have been discovered in adults, and we would now like to test what they are doing in childhood and adolescents in the CO90s. To do this, we’d like to link the gene variants we are finding in adults to body fat imaging and circulating blood markers at all time points in childhood and adolescence where available. We’d like to analyse the parent’s data to help in the discovery of these genetic variants by analysing with other large studies of adults.

Impact of research: 
We've had a lot of interest from our three papers (all in Diabetes) on discovering these unusual variants. Most recently we had considerable interest from the media when we used these variants as an "instrument" to "uncouple" higher adiposity from it's adverse effects to show (subject to wide confidence intervals) that higher adiposity without it's adverse effects had a similar effect on depression as standard higher BMI. Our work will add to other important work in CO90s in understanding the causes and consequences of obesity in children and young adults. In the next few years it will be very interesting to see how these variants affect the offspring of C090s.
Date proposal received: 
Friday, 14 December, 2018
Date proposal approved: 
Tuesday, 18 December, 2018
Keywords: 
Genetics, Obesity, GWAS, Medical imaging, Metabolomics, NMR, BMI, Genetic epidemiology, Genetics, Genome wide association study, Liver function, Mendelian randomisation, Metabolic - metabolism