The Genetics of type 2 diabetes aetiology and progression
Approved Research ID: 9055
Approval date: January 5th 2015
Lay summaryOur research question is `what are the genetic factors that predispose individuals to type 2 diabetes and what are the genetic factors that mean some diabetic individuals' condition progresses faster than others?`. We aim to use the UK Biobank to identify genetic factors that: i) predispose some individuals to type 2 diabetes. We will include genetic analyses of the traits that are associated with T2D. ii) predipose some individuals to deteriorate quicker than others. We will use the time it takes an indvidual to progress to insulin treatment or those who develop heart disease as measures of diabetes disease progression. Our proposed research will address a fundamental health question - why do some individuals develop type 2 diabetes in today's obesogenic environment whilst others do not? There is very strong evidence that genetic factors account for some of these differences between individuals and yet we have not identified a large component of the genetic heritability of type 2 diabetes. We also know little about the genetic factors that may lead to some type 2 diabetic individuals requiring insulin or having heart attacks earlier than others. Our proposal will proceed in two phases. In phase 1 we will analyse all the genetic variants measured in the approximately 150,000 individuals that will be genotyped by the end of 2014. We will analyse the approximately 800,000 genetic variants against intermediate traits, type 2 diabetes status in all individuals, and within the type 2 diabetic individuals, against time to insulin, treatment, measures of macro and micro vascular disease and age at diagnosis of diabetes. In phase 2 we will repeat these analyses but using the full dataset of 500,000 individuals and HBA1C measures. In phase 1 the 150,000 with genotype data at end 2014 and in phase 2 the full 500,000. We estimate that the full 500,000 includes 14,000-20,000 type 2 diabetic cases depending on the use of HBA1C criteria and how type 1 diabetes is excluded. Some of our secondary-questions such as time to insulin and micor and macro vascular status are applicable only to those we have classified (at baseline) as type 2 diabetic. See Tyrrell et al, IJE our publication on parental diabetes and birth weight.
- Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank
- Genetic evidence for causal relationships between maternal obesity-related traits and birth weight
- Variants in the FTO and CDKAL1 loci have recessive effects on risk of obesity and type 2 diabetes, respectively
- Quantifying the extent to which index event biases influence large genetic association studies
- Genetic evidence for a link between favorable adiposity and lower risk of type 2 diabetes, hypertension and heart disease.
- A single nucleotide polymorphism genetic risk score to aid diagnosis of coeliac disease: a pilot study in clinical care