Principal Investigator: Professor Nilesh Samani
Department: Department of Cardiovascular Sciences
Institution: University of LeicesterTags: 9922, CAD, gene-environment, genetics, risk prediction
1a: Coronary heart disease (CHD) and heart attack is caused by a combination of inherited and lifestyle/environmental factors. 17,000 new cases of CHD are expected to develop in the UK Biobank participants by 2017. The aims of our research are use the genetic data being generated in UK Biobank to identify genes that affect risk of CHD, investigate whether specific genes and certain lifestyle factors such as smoking interact to increase risk, determine whether adding genetic information can improve prediction of CHD, and identify causal mechanisms for CHD that can be targeted to develop new treatments.
1b: UK Biobank was established to improve understanding of the causes of common diseases and particularly the interaction between genes and environment and life-style factors. CHD is the commonest cause of death and disability world-wide. It is the archetypal disease caused by an interaction between inherited and environmental/lifestyle factors. Our research will improve understanding of the genetic causes of CHD, how these interact with environmental/lifestyle factors and how the findings can be applied to improving prediction, prevention and treatment of CHD.
1c: We will divide the UK Biobank participants into those with CHD (cases) and those without (controls) and compare their genetic information generated using the UK Biobank array to identify genetic variants that are associated with development of CHD. We will use lifestyle/environmental information collected on participants to see if there is an interaction between such factors (e.g smoking) and genes in increasing CHD risk. We will investigate whether adding genetic information to current methods can improve prediction of development of CHD. We will use genetic approaches to define the best targets to develop drugs against to tackle CAD
1d: We plan to use the full cohort for our studies.
PROJECT EXTENSION – APPROVED 01.11.2016
“I am writing to seek approval of some additional analysis we wanted to do in UK Biobank under the above application. Specifically there are two analysis which both fit overall within Objective 3 of our approved application:
1. Under this objective we already have approval to use genetic approaches to undertake causal association of suspected risk factors/traits with CAD. As part of this work we were planning to follow-up our previously published work (Nelson et al. NEJM 2015) suggesting that the inverse association of height with CAD may be causal. In addition to CAD, we would like to extend this analysis to other diseases and traits recorded in UK Biobank to see if the association with CAD is specific or not and which of any additional relationships are causal.
2. Under the same overall objective we would also like to use genetic approaches to identify (predict) any possible side effects of cardiovascular drugs by using genetic variants that affect the activity of the target of drug as proxies.”