UCL Institute of Cardiovascular Science
Genetic epidemiology and translational cardiovascular genomics
Genetic epidemiology involves the identification of DNA sequence differences that underlie observable biological differences and disease susceptibility. This is of interest because of the unique insight on causation that genetic studies offer. Genotypes are unique among naturally occurring differences between individuals in being allocated by a random assortment at conception (according to Mendel’s Laws), which means that confounding factors are balanced among individuals of differing genotypes in populations, making genetic studies akin to randomised controlled clinical trials. Moreover, since genotype is not modifiable, reverse causality is also overcome in genetic studies.
Our work is funded by the British Heart Foundation, Medical Research Council, Rosetrees Trust, National Institute of Health Research and the UCL BRC Therapeutic Innovation Fund.
Key research activities
Working with excellent support facilities and expertise at UCL Genetics Institute, UCL Genomics, the Bloomsbury Centre for Statistical Genetics and Epidemiology, and other collaborators, group members utilise high-throughput genotyping technology to help identify single nucleotide polymorphisms (and other type of genetic variation) that influence individual differences in disease-relevant biomarkers and the risk of cardiovascular events.
At the heart of this programme of research is a near unique cluster of large population-based cohort studies based at UCL/LSHTM (including the Whitehall II study, the English Longitudinal Study of Ageing [ELSA], the British Regional Heart Study [BRHS], the British Women’s Heart and Health Study, the Northwick Park Heart Study II [NPHS II], the MRC National Survey of Health and Development and others) comprising in aggregate around 30,000 subjects with multiple phenotypic measures. This work is now supported by a new 5-year BHF programme for Applied and Translational Cardiovascular Genomics which started in January 2011. This links epidemiologists, statisticians and other experts, as well as several large population studies, in a new framework, the UCL-LSHTM-Edinburgh and Bristol (UCLEB) Consortium.
This work stream utilises the new genetic findings and the principles of Mendelian randomisation:
- To confirm or refute the causal role of specific emerging risk factors for cardiovascular disease including homocysteine, C-reactive protein, Lp(a) and fibrinogen (Mendelian randomisation for biomarker validation)
- To understand the mechanisms linking genetic variation with disease susceptibility based on the premise that the shape and strength of genetic associations with risk factors that lie on the causal pathway should be concordant with observed genetic associations with disease end-points.
- To help pioneer the use of genetic studies in populations as natural randomised trials to help validate specific drug targets for the treatment or prevention of cardiometabolic disease (Mendelian randomisation for drug target validation).
Projects of this type co-ordinated by the Genetic Epidemiology Group now link hundreds of investigators worldwide, with typical sample sizes for much of the work now exceeding 100,000 subjects, helping to provide precise and reliable findings.
Work in this stream critically evaluates the role of genotype as a tool for prediction of disease risk and drug response (pharmacogenetics).