B4615 - Whole-exome sequencing as a tool to reveal rare genetic architecture of diabetes - 16/05/2024

B number: 
Principal applicant name: 
Marisa Canadas Garre | University of Bristol (United Kingdom)
Professor Nicholas Timpson, Dr Laura Corbin, Dr Laurie Fabian
Title of project: 
Whole-exome sequencing as a tool to reveal rare genetic architecture of diabetes
Proposal summary: 

People with diabetes taking insulin sometimes present resistance or failure to this therapy. Investigating the genetic factors influencing the resistance to insulin in people with diabetes may lead to biological insights into the causes of failure to this therapy and help improving their long-term health.
We will look into the DNA of ALSPAC participants that codes the proteins, to identify rare variants (those with a frequency <0.1%) that have a high impact on the structure and/or function of the protein. Then we will investigate if those variants have an influence on the risk of diabetes, and if they have an impact on the levels of diabetes-related traits, as insulin, glucose, etc.

Impact of research: 
Greater understanding of the aetiology of diabetes and especially insulin resistance. This study will help identify novel genetic variants involved insulin resistance and may reveal potential targets for therapy and drug development.
Date proposal received: 
Monday, 13 May, 2024
Date proposal approved: 
Thursday, 16 May, 2024
Genetic epidemiology (including association studies and mendelian randomisation), Diabetes, Obesity, Computer simulations/modelling/algorithms, DNA sequencing, Gene mapping, GWAS, Metabolomics, Statistical methods, Ageing, Biological samples -e.g. blood, cell lines, saliva, etc., Whole genome sequencing, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., BMI, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Metabolic - metabolism, Statistical methods, Whole Exome Sequencing